Search Results (60)

The use of temporary mechanical circulatory support in refractory heart failure cardiogenic shock (HFCS) has risen, leading to potential complications. Post-Cardiac Injury Syndrome (PCIS) from Impella insertion is rare but may result from subclavian artery manipulation and aortic irritation. We report the first case of pericarditis (PCIS) caused by Impella 5.5 insertion in an HFCS patient awaiting heart transplantation. The patient developed chest pain, tachycardia, and hypotension post-Impella insertion. Laboratory results and electrocardiograms confirmed PCIS. Treatment with Ibuprofen and Colchicine was successful. He received a heart transplant 14 days later. This case emphasizes recognizing iatrogenic pericarditis after Impella insertion and the need to avoid additional myocardial strain. Full article

Heart failure is a heterogeneous disorder that can lead to cardiogenic shock. Mechanical circulatory support (MCS) devices can replace the cardiac function in an attempt to bridge patients to transplant or they can serve as destination therapy to improve overall patient functionality and in turn quality of life. Currently utilized MCS devices include devices such as Left Ventricular Assist Devices (LVADs), Biventricular Assist Devices (BiVADs), Impella, Total Artificial Hearts (TAHs), and extracorporeal membrane oxygenation (ECMO). This literature review examines a range of studies, case reports, and meta-analyses to present current approaches to mechanical circulatory support (MCS), along with the challenges and limitations of existing devices, common complications, and overall survival and long-term outcomes following MCS therapy. Full article

Background: Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease (CAD) that is characterized by concentric fibrous intimal hyperplasia along the length of coronary vessels, and is recognized as long-term complication after heart transplantation. The chromosomal loci 9p21, 6q25.1, and 2q36.3, represented by their respective leading variants rs10757274, rs6922269 and rs2943634, have been linked with a history of CAD by genome-wide association studies. We aimed to investigate the associations of genetic variants at the loci 9p21, 6q25.1, and 2q36.3 with CAV as genetic risk factors for early prediction. Methods: Genomic DNA was extracted from paired aortic samples of 727 heart recipients (average age 50.8 ± 12.2 years; 21.3% women) and corresponding donors (average age 39.7 ± 12.0 years; 26.1% women). The variants within the loci 9p21, 6q25.1, and 2q36.3 were genotyped using PCR-RFLP. Results: The recipients’ variants of 9p21 (OR 1.97; 95% CI, 1.21-3.19 for GG vs. +A comparison, p = 0.0056) and 2q36.3 (OR 2.46; 95% CI, 1.12–6.17 for +C vs. AA comparison, p = 0.0186) were associated with higher incidence of CAV during the first year following heart transplantation. No such association was found for donor genotypes. Conclusions: Our data suggest that variants at the locus 9p21 (rs10757274) and 2q36.3 (rs2943634) are associated with early CAV development. Full article

The advancement of medical 3D printing technology includes several enhancements, such as decreasing the length of surgical procedures and minimizing anesthesia exposure, improving preoperative planning, creating personalized replicas of tissues and bones specific to individual patients, bioprinting, and providing alternatives to human organ transplants. The range of materials accessible for 3D printing within the healthcare industry is significantly narrower when compared with conventional manufacturing techniques. Liquid silicone rubber (LSR) is characterized by its remarkable stability, outstanding biocompatibility, and significant flexibility, thus presenting substantial opportunities for manufacturers of medical devices who are engaged in 3D printing. The main objective of this study is to develop, refine, and assess a 3D printer that can employ UV-cured silicone for the fabrication of aortic heart valves. Additionally, the research aims to produce a 3D-printed silicone aortic heart valve and evaluate the feasibility of the final product. A two-level ANOVA experimental design was utilized to investigate the impacts of print speed, nozzle temperature, and layer height on the print quality of the aortic heart valve. The findings demonstrated that the 3D-printed heart valve’s UV-cured silicone functioned efficiently, achieving the target flow rates of 5 L/min and 7 L/min. Two distinct leaflet thicknesses (LT) of the heart valve, namely 0.8 mm and 1.6 mm, were also analyzed to simulate calcium deposition on the leaflets. Full article

The discovery of hypertrophic cardiomyopathy (HCM) dates back to 1958, when the pathologist Donald Teare of the St. George’s Hospital in London performed autopsies in eight cases with asymmetric hypertrophy of the ventricular septum and bizarre disorganization (disarray) at histology, first interpreted as hamartoma. Seven had died suddenly. The cardiac specimens were cut along the long axis, similar to the 2D echo. In the same year, at the National Institute of Health U.S.A., Eugene Braunwald, a hemodynamist, and Andrew Glenn Morrow, a cardiac surgeon, clinically faced a patient with an apparently similar morbid entity, with a systolic murmur and subaortic valve gradient. “Discrete” subaortic stenosis was postulated. However, at surgery, Dr. Morrow observed only hypertrophy and performed myectomy to relieve the obstruction. This first Braunwald–Morrow patient underwent a successful cardiac transplant later at the disease end stage. The same Dr. Morrow was found to be affected by the familial HCM and died suddenly in 1992. The term “functional subaortic stenosis” was used in 1959 and “idiopathic hypertrophic subaortic stenosis” in 1960. Years before, in 1957, Lord Brock, a cardiac surgeon at the Guy’s Hospital in London, during alleged aortic valve surgery in extracorporeal circulation, did not find any valvular or discrete subaortic stenoses. In 1980, John F. Goodwin of the Westminster Hospital in London, the head of an international WHO committee, put forward the first classification of heart muscle diseases, introducing the term cardiomyopathy (dilated, hypertrophic, and endomyocardial restrictive). In 1995, the WHO classification was revisited, with the addition of two new entities, namely arrhythmogenic and purely myocardial restrictive, the latter a paradox of a small heart accounting for severe congestive heart failure by ventricular diastolic impairment. A familial occurrence was noticed earlier in HCM and published by Teare and Goodwin in 1960. In 1989–1990, the same family underwent molecular genetics investigation by the Seidman team in Boston, and a missense mutation of the β-cardiac myosin heavy chain in chromosome 14 was found. Thus, 21 years elapsed from HCM gross discovery to molecular discoveries. The same original family was the source of both the gross and genetic explanations of HCM, which is now named sarcomere disease. Restrictive cardiomyopathy, characterized grossly without hypertrophy and histologically by myocardial disarray, was found to also have a sarcomeric genetic mutation, labeled “HCM without hypertrophy”. Sarcomere missense mutations have also been reported in dilated cardiomyopathy (DCM) and non-compaction cardiomyopathy. Moreover, sarcomeric gene defects have been detected in some DNA non-coding regions of HCM patients. The same mutation in the family may express different phenotypes (HCM, DCM, and RCM). Large ischemic scars have been reported by pathologists and are nowadays easily detectable in vivo by cardiac magnetic resonance with gadolinium. The ischemic arrhythmic substrate enhances the risk of sudden death. Full article

Glycine, a simple amino acid, is not only essential due to its potential insufficiency in vivo, but also has significant metabolic functions. It serves as a crucial building block for proteins. At the same time, as a bioactive molecule, it regulates gene expression for cytoprotection, protein configuration and activity, and other critical biological processes, including glutathione synthesis. The intriguing, beneficial effects of glycine in medical applications have piqued the research community’s interest in recent decades. This work delves into the compelling discoveries about the pivotal role of glycine in cardiovascular health and its intricate mechanisms of action for alleviating several medical conditions. Glycine’s broad spectrum of impact spans numerous diseases, encompassing not only acute myocardial infarction, aortic dissection, and cardiac hypertrophy, but also transplant rejections of aortic allografts, insulin resistance, and endothelial dysfunction, thereby providing a comprehensive understanding of its medical applications. Full article

Background: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW’s feasibility in the prognostic stratification of AdHF. Methods: We retrospectively screened patients with AdHF who accessed our hospital in 2018–2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). Results: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50–62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323–868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan–Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. Conclusions: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy. Full article

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding. Full article

Percutaneous mechanical circulatory support (MCS) devices are designed for short-term treatment in cases of acute decompensated heart failure as a bridge to transplant or recovery. Some of the known complications of MCS treatments are related to their hemodynamics in the aorta. The current study investigates the effect of MCS on the aortic flow. The study uses combined experimental and numerical methods to delineate complex flow structures. Particle image velocimetry (PIV) is used to capture the vortical and turbulent flow characteristics in a glass model of the human aorta. Computational fluid dynamics (CFD) analyses are used to complete the 3D flow in the aorta. Three specific MCS configurations are examined: a suction pump with a counterclockwise (CCW) rotating impeller, a suction pump with a clockwise (CW) rotating impeller, and a discharge pump with a straight jet. These models were examined under varying flow rates (1–2.5 L/min). The results show that the pump configuration strongly influences the flow in the thoracic aorta. The rotating impeller of the suction pump induces a dominant swirling flow in the aorta. The swirling flow distributes the incoming jet and reduces the turbulent intensity near the aortic valve and in the aorta. In addition, at high flow rates, the local vortices formed near the pump are washed downstream toward the aortic arch. Specifically, an MCS device with a CCW rotating impeller induces a non-physiological CCW helical flow in the descending aorta (which is opposite to the natural helical flow), while CW swirl combines better with the natural helical flow. Full article

Patients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented. Full article

Background: Phrenic nerve injury is a devastating complication that results in significant morbidity and mortality. We developed a novel technique to localize the phrenic nerve and evaluate its success. Methods: Two groups of children underwent repeat sternotomy for a variety of indications. Group I (69 patients, nerve stimulator) and Group II (78 patients, no nerve stimulator). Results: There was no significant difference in the mean age and weight between the two groups: (6.4 ± 6.5 years vs. 5.6 ± 6.4 years; p = 0.65) and (25.2 ± 24.1 vs. 22.6 ± 22.1; p = 0.69), respectively. The two groups were comparable in the following procedures: pulmonary conduit replacement, bidirectional cavopulmonary anastomosis, aortic arch repair, and Fontan, while Group I had more pulmonary arterial branch reconstruction (p = 0.009) and Group II had more heart transplant patients (p = 0.001). There was no phrenic nerve injury in Group I, while there were 13 patients who suffered phrenic nerve injury in Group II (p < 0.001). No early mortality in Group I, while five patients died prior to discharge in Group II. Eleven patients underwent diaphragm plication in Group II (p = 0.001). The mean number of hours on the ventilator was significantly higher in Group II (137.3 ± 324.9) compared to Group I (17 ± 66.9), p < 0.001. Group II had a significantly longer length of ICU and hospital stays compared to Group I (p = 0.007 and p = 0.006 respectively). Conclusion: Phrenic nerve injury in children continues to be associated with significant morbidities and increased length of stay. The use of intraoperative phrenic nerve stimulator can be an effective way to localize the phrenic nerve and avoid its injury. Full article

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. Full article

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and the Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative assessment of the achievable degree of assistance. In this paper, we analyse the interaction between the Impella 2.5 pump applied as the LVAD and IABP using the numerical simulator of the cardiovascular system developed in our laboratory. Starting with pathological conditions reproduced using research data, the simulations were performed by setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects induced by drug administration during the assistance were also simulated. The haemodynamic parameters under investigation were aa follows: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in this study were as follows: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow further stabilisation and transfer to a transplant centre should the escalation of treatment be required. Full article

Background: When heart transplantation and myocardial recovery are unlikely, patients presenting with biventricular cardiogenic shock initially treated with extracorporeal membrane oxygenation (ECMO) may benefit from a mechanical support upgrade. In this scenario, a micro-invasive approach is proposed: the combination of the double-lumen ProtekDuo cannula (Livanova, London, UK) and the Impella 5.5 (Abiomed, Danvers, MA) trans-aortic pump that translates into a hybrid BiVAD. Methods: All consecutive ECMO patients presenting with biventricular cardiogenic shock and ineligibility to heart transplantation from August 2022 were prospectively enrolled. The clinical course, procedural details, and in-hospital events were collected via electronic medical records. Results: A total of three patients, who were temporarily not eligible for heart transplantation or durable LVAD due to severe acute pneumonia and right ventricular (RV) dysfunction, were implanted with a hybrid BiVAD. This strategy provided high-flow biventricular support while pulmonary function ameliorated. Moreover, by differentially sustaining the systemic and pulmonary circulation, it allowed for a more adequate reassessment of RV function. All the patients were considered eligible for isolated durable LVAD and underwent less invasive LVAD implantation paired with a planned postoperative RVAD. In all cases, RV function gradually recovered and the RVAD was successfully removed. Conclusions: The Hybrid BiVAD represents an up-to-date micro-invasive mechanical treatment of acute biventricular failure beyond ECMO. Its rationale relies on more physiological circulation across the lungs, the complete biventricular unloading, and the possibility of including an oxygenator in the circuit. Finally, the independent and differential control of pulmonary and systemic flows allows for more accurate RV function evaluation for isolated durable LVAD eligibility reassessment. Full article

Ischemia–reperfusion injury (IRI) in the myocardium has been thoroughly researched, especially in acute coronary syndrome and heart transplantation. However, our understanding of IRI implications on cardiac valves is still developing. This knowledge gap becomes even more pronounced given the advent of partial heart transplantation, a procedure designed to implant isolated human heart valves in young patients. This study aims to investigate the effects of IRI on aortic valvular endothelial cells (VECs), valvular interstitial cells (VICs), and whole leaflet cultures (no separation of VECs and VICs). We employed two conditions: hypoxic cold storage reperfusion (HCSR) and normothermia (NT). Key markers, secreted protein acidic and cysteine rich (SPARC) (osteonectin), and inducible nitric oxide synthase (iNOS2) were evaluated. In the isolated cells under HCSR, VICs manifested a significant 15-fold elevation in SPARC expression compared to NT (p = 0.0016). Conversely, whole leaflet cultures exhibited a 1-fold increment in SPARC expression in NT over HCSR (p = 0.0011). iNOS2 expression in VECs presented a marginal rise in HCSR, whereas, in whole leaflet settings, there was a 1-fold ascent in NT compared to HCSR (p = 0.0003). Minor escalations in the adhesion molecules intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), E-selection, and P-selection were detected in HCSR for whole leaflet cultures, albeit without statistical significance. Additionally, under HCSR, VICs released a markedly higher quantity of IL-6 and IL-8, with respective p-values of 0.0033 and <0.0001. Interestingly, the IL-6 levels in VECs remained consistent across both HCSR and NT conditions. These insights lay the groundwork for understanding graft IRI following partial heart transplantation and hint at the interdependent dynamic of VECs and VICs in valvular tissue. Full article