Surgical Challenges in Infective Endocarditis: State of the Art.

Infective endocarditis (IE) is still a life-threatening disease with frequent lethal outcomes despite the profound changes in its clinical, microbiological, imaging, and therapeutic profiles. Nowadays, the scenario for IE has changed since rheumatic fever has declined, but on the other hand, multiple aspects, such as elderly populations, cardiovascular device implantation procedures, and better use of multiple imaging modalities and multidisciplinary care, have increased, leading to escalations in diagnosis. Since the ESC and AHA Guidelines have been released, specific aspects of diagnostic and therapeutic management have been clarified to provide better and faster diagnosis and prognosis. Surgical treatment is required in approximately half of patients with IE in order to avoid progressive heart failure, irreversible structural damage in the case of uncontrolled infection, and the prevention of embolism. The timing of surgery has been one of the main aspects discussed, identifying cases in which surgery needs to be performed on an emergency (within 24 h) or urgent (within 7 days) basis, irrespective of the duration of antibiotic treatment, or cases where surgery can be postponed to allow a brief period of antibiotic treatment under careful clinical and echocardiographic observation. Mainly, guidelines put emphasis on the importance of an endocarditis team in the handling of systemic complications and how they affect the timing of surgery and perioperative management. Neurological complications, acute renal failure, splenic or musculoskeletal manifestations, or infections determined by multiresistant microorganisms or fungi can affect long-term prognosis and survival. Not to be outdone, anatomical and surgical factors, such as the presence of native or prosthetic valve endocarditis, a repair strategy when feasible, anatomical extension and disruption in the case of an annular abscess (mitral valve annulus, aortic mitral curtain, aortic root, and annulus), and the choice of prosthesis and conduits, can be equally crucial. It can be hard for surgeons to maneuver between correct pre-operative planning and facing unexpected obstacles during intraoperative management. The aim of this review is to provide an overview and analysis of a broad spectrum of specific surgical scenarios and how their challenging management can be essential to ensure better outcomes and prognoses.

Intracardiac hematoma treated conservatively by ECMO support.

Clinical pathway of an intracardiac hematoma treated by ECMO support.

Role of Oxidative Stress and Autophagy in Thoracic Aortic Aneurysms.

Thoracic aortic aneurysms (TAA) pathogenesis and progression include many mechanisms. The authors investigated the role of autophagy, oxidative stress, and endothelial dysfunction in 36 TAA patients and 23 control patients. Univariable and multivariable analyses were performed. TAA patients displayed higher oxidative stress and endothelial dysfunction then control patients. Autophagy in the TAA group was reduced. The association of oxidative stress and autophagy with aortic disease supports the role of these processes in TAA. The authors demonstrate a putative role of Nox2 and autophagy dysregulation in human TAA. These findings could pinpoint novel treatment targets to prevent or limit TAA progression.

Single-center experience with partial support device in destination therapy for end-stage heart failure.

Ventricular assist devices (VADs) are considered the standard of care for end-stage heart failure (HF) patients. Despite increasing confidence in the technology, evidence data, endorsement by scientific societies and guidelines, the number of implants reached a steady state and is not increasing at the expected pace. This is most likely related to complications that are still burdening the technology and consequently excluding the most needy, ill, and fragile population. In this manuscript we are reporting a single-center experience in a very fragile, elderly and end-stage HF population, with a superficial, partial support device: the CircuLite Synergy. The patients were included in the pre-CE mark clinical study and consequently the device underwent technical adjustment during the support, based on the complications recorded. At our institution were implanted 6 patients overall: 3 patients survived to discharge and 2 survived up to 5 years. Most of the complications recorded were due to patients' frailty and overall clinical conditions. The initial experience with the CircuLite Synergy device is proving that a more "superficial" device might be more tolerable in an elderly, frail population. Partial support has proven hemodynamically efficacious and efficient in relieving heart failure symptoms, improving medical therapy tolerability, and improving quality of life. Unfortunately, the technology was not made available due to financial uncertainty and poor management, but we hope that once the concept has been proved someone will collect the legacy.

Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome.

Bicuspid aortic valve (BAV) disease is recognized to be a syndrome with a complex and multifaceted pathophysiology. Its progression is modulated by diverse evolutionary conserved pathways, such as Notch-1 pathway. Emerging evidence is also highlighting the key role of TLR4 signaling pathway in the aortic valve pathologies and their related complications, such as sporadic ascending aorta aneurysms (AAA). Consistent with these observations, we aimed to evaluate the role of TLR4 pathway in both BAV disease and its common complication, such as AAA. To this aim, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 ± 12.8 years), with and without AAA were enrolled. Plasma assessment, tissue and gene expression evaluations were performed. Consistent with data obtained in the previous study on immune clonotypic T and B altered responses, we found reduced levels of systemic TNF-α, IL-1, IL-6, IL-17 cytokines in BAV cases, either in the presence or absence of AAA, than TAV cases (p < 0.0001 by ANOVA test). Interestingly, we also detected reduced levels of s-TLR4 in BAV cases with or without AAA in comparison to the two groups of TAV subjects (p < 0.0001 by ANOVA test). These results may suggest a deregulation in the activity or in the expression of TLR4 signaling pathway in all BAV cases. Portrait of these data is, indeed, the significantly decreased gene expression of inflammatory cytokines and TLR4, in both normal and aneurysmatic tissue samples, from BAV with AAA than TAV with AAA. In conclusion, our study demonstrates that subjects with BAV display a significant deregulation of TLR4 signaling pathway paralleled by a deregulation of Notch-1 pathway, as previously showed. This data suggests that the crosstalk between the Notch-1 and TLR4 signaling pathways may play a crucial role in both physiological embryological development, and homeostasis and functionality of aortic valve in adult life.

Comparative spallation performance of silicone versus Tygon extracorporeal circulation tubing.

OBJECTIVES: Reports ranged from mixed to marginal tubing wear and spallation effects as a complication of roller pumps in cardiopulmonary bypass (CPB). Because the rollers constantly compress part of the tubing, we sought to determine whether circuit materials behave differently under a 3-h simulation of CPB. METHODS: Two different tubing materials (silicone and Tygon) were tested with a customized experimental circuit, designed to allow in vitro simulation of CPB with priming volumes, pressures, revolutions per minute and temperatures equivalent to the clinical scenario. Samples were analysed with optical and field-emission scanning electron microscopy. We collected 200-ml fluid samples at 4 different times: before starting the CPB (T0), when the predicted revolutions per minute corresponded to about 2 min of CPB (T1), at 90 min (T2) and at 180 min (T3). At the end of CPB, we harvested 2 samples of tubing. Lastly, optical investigations and field-emission scanning electron microscopy observations were used for qualitative and quantitative analysis of circulating fragments. RESULTS: T2 and T3 fluid samples showed more particles than T1 samples. Significant differences in terms of particle numbers were detected: silicone tubing released more fragments per millilitre than Tygon tubing, with both materials releasing particles from 5 to 500 µm. Silicone tubing was associated with a time-dependent increase in small particles released (P = 0.04), whereas this did not apply to large particles or to Tygon tubing. Yet, bootstrap estimates suggested that silicone tubing was associated with the release of more small particles whereas Tygon tubing released more large particles (both P < 0.01). Unlike silicone, Tygon samples taken from the portion of the circuit not subjected to the action of the roller pump did not show any erosion on their surfaces. Samples of both materials taken from the portion subjected to the compression of the roller pump showed signs of significant deterioration. CONCLUSIONS: Silicone showed a worse spallation performance than Tygon, thus appearing less safe for more complex surgery of prolonged duration or for patients with a prior cerebral ischaemic event. Additional risk and cost-effectiveness comparisons to determine the potential benefits of one type of tubing material over the other are warranted to further expand our findings.

A network meta-analysis of randomized trials and observational studies on left ventricular assist devices in adult patients with end-stage heart failure.

OBJECTIVES: The use of left ventricular assist devices (LVADs) is an approved treatment option for end-stage heart failure. Several devices have been developed over the years, including 2 newer ones (HeartMate 3 and HeartWare), but an overall comparative analysis has never been performed. We conducted a network meta-analysis of randomized trials on LVAD for adults with end-stage heart failure. METHODS: Pertinent studies were searched in several databases. Selected outcomes were extracted, including death, stroke and bleeding. Incident relative risks were computed with network meta-analysis with 95% confidence intervals (CIs) and P-scores (with highest values indicating the best therapy). RESULTS: Four randomized clinical trials and 4 observational studies were identified, totalling 2248 patients. Using HeartMate XVE/VE as the benchmark, all LVADs provided a significant better outcome for survival rate in comparison with medical therapy, without significant differences among newer LVADs. The relative risk for death was 0.79 (95% 0.60-1.04; P-score 0.89) for HeartMate II, 0.85 (95% CI 0.62-1.17; P-score 0.64) for HeartWare, 0.88 (95% CI 0.59-1.31; P-score 0.60) for HeartMate 3 and 1.48 (95% CI 1.21-1.80; P-score 0.01) for medical management. While appraising other outcomes, new generation devices (HeartMate 3 and HeartWare) proved better than older generation devices for bleeding, device thrombosis, hepatic dysfunction, renal dysfunction, respiratory dysfunction, right ventricular failure and sepsis with significant differences among them. CONCLUSIONS: In the management of end-stage heart failure, LVADs provided significant improvement in terms of survival rate compared to medical therapy, but no significant differences exist among LVADs. Despite the reduction of adverse events over time, further technological refinements will be crucial to improve this technology to better address decision-making and to improve clinical outcomes.

Surgical embolectomy for acute massive pulmonary embolism: state of the art.

Massive pulmonary embolism (PE) is a severe condition that can potentially lead to death caused by right ventricular (RV) failure and the consequent cardiogenic shock. Despite the fact thrombolysis is often administrated to critical patients to increase pulmonary perfusion and to reduce RV afterload, surgical treatment represents another valid option in case of failure or contraindications to thrombolytic therapy. Correct risk stratification and multidisciplinary proactive teams are critical factors to dramatically decrease the mortality of this global health burden. In fact, the worldwide incidence of PE is 60-70 per 100,000, with a mortality ranging from 1% for small PE to 65% for massive PE. This review provides an overview of the diagnosis and management of this highly lethal pathology, with a focus on the surgical approaches at the state of the art.

The Biological Mechanisms of Action of Cardiac Progenitor Cell Therapy.

PURPOSE OF REVIEW: Cell therapy for cardiovascular diseases is regarded as a rapidly growing field within regenerative medicine. Different cellular populations enriched for cardiac progenitor cells (CPCs), or derivate a-cellular products, are currently under preclinical and clinical evaluation. Here, we have reviewed the described mechanisms whereby resident post-natal CPCs, isolated in different ways, act as a therapeutic product on the damaged myocardium. RECENT FINDINGS: Several biological mechanisms of action have been described which can explain the multiple therapeutic effects of CPC treatment observed on cardiac function and remodelling. These mechanisms span from direct cardiovascular differentiation, through induction of resident progenitor proliferation, to paracrine effects on cardiac and non-cardiac cells mediated by exosomes and non-coding RNAs. All the reported mechanisms of action support an integrated view including cardiomyogenesis, cardioprotection, and anti-fibrotic effects. Moreover, future developments of CPC therapy approaches may support cell-free strategies, exploiting effective pleiotropic cell-derived products, such as exosomes.

Cerebrovascular Complications and Infective Endocarditis: Impact of Available Evidence on Clinical Outcome.

Background. Infective endocarditis (IE) is a life-threatening disease. Its epidemiological profile has substantially changed in recent years although 1-year mortality is still high. Despite advances in medical therapy and surgical technique, there is still uncertainty on the best management and on the timing of surgical intervention. The objective of this review is to produce further insight into the short- and long-term outcomes of patients with IE, with a focus on those presenting cerebrovascular complications.

Recent Developments in Minimally Invasive Cardiac Surgery: Evolution or Revolution?

Intraluminal aortic clamping has been achieved until now by means of a sophisticated device consisting of a three-lumen catheter named Endoclamp, which allows at the same time occlusion of the aorta, antegrade delivering of cardioplegia, and venting through the aortic root. This tool has shown important advantages allowing aortic occlusion and perfusate delivering without a direct contact with ascending aorta reducing meanwhile the risk of traumatic and/or iatrogenic injuries. Recently, a new device (Intraclude catheter) with the same characteristics and properties has been proposed and introduced in clinical practice. The aim of this paper is to investigate the differences between Endoclamp and Intraclude catheters and to analyze the advantages advocated by this new device for intraluminal aortic occlusion since it is noticeable as these new technological tools are gaining more and more attractiveness due to their appraised clinical efficacy.