Evolocumab Treatment in Dyslipidemic Patients Undergoing Coronary Artery Bypass Grafting: One-Year Safety and Efficacy Results.

Background: The inhibition of PCSK9 lowered LDL cholesterol levels, reducing the risk of cardiovascular events. However, the effect on patients who have undergone surgical myocardial revascularization has not yet been evaluated. Methods: From January 2017 to December 2022, 180 dyslipidemic patients who underwent coronary artery bypass were included in the study. Until December 2019, 100 patients optimized therapy with statin ± ezetimibe (SG). Since January 2020, 80 matched patients added treatment with Evolocumab every 2 weeks (EG). All 180 patients were followed-up at 3 and 12 months, comparing outcomes. Results: The two groups are homogenous. At 3 months and 1 year, a significant decrease in the parameter mean levels of LDL cholesterol and total cholesterol is detected in the Evolocumab group compared to the standard group. No mortality was detected in either group. No complications or drug discontinuation were recorded. In the SG group, five patients (5%) suffered a myocardial infarction during the 1-year follow-up. In the EG group, two patients (2.5%) underwent PTCA due to myocardial infarction. There is no significant difference in overall survival according to the new treatment (p-value = 0.9), and the hazard ratio is equal to 0.94 (95% C.I.: [0.16-5.43]; p-value = 0.9397). Conclusions: The use of Evolocumab, which was started immediately after coronary artery bypass graft surgery, significantly reduced LDL cholesterol and total cholesterol levels compared to statin treatment alone and is completely safe. However, at one year of follow-up, this result did not have impact on the reduction in major clinical events.

Prognostic role of endocarditis in isolated tricuspid valve surgery. A propensity-weighted study.

OBJECTIVES: The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. METHODS: The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n = 406, 55 ± 16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n = 107 vs Not-IE group n = 299). RESULTS: No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE = 6.8%; OR = 0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p = 0.01). The composite endpoint of cardiac death and reoperation at 6 years was reduced in the Group IE (63.2 ± 6.8% vs 78.9 ± 3.1%; p = 0.022). Repair strategy resulted in an increased late survival even in IE cases. CONCLUSIONS: Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes.

Circulating Levels of Ferritin, RDW, PTLs as Predictive Biomarkers of Postoperative Atrial Fibrillation Risk after Cardiac Surgery in Extracorporeal Circulation.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haematological parameters as POAF risk biomarkers in patients subjected to cardiac surgery. We enrolled 105 patients (mean age = 70.1 ± 7.1 years; 70 men and 35 females) with diverse heart pathologies and who were subjected to cardiothoracic surgery. Their blood samples were collected and used to determine hematological parameters. Electrocardiographic and echocardiographic parameters were also evaluated. The data obtained demonstrated significantly higher levels of serum ferritin, red cell distribution width (RDW), and platelets (PLTs) in POAF patients. However, the serum ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥148.5 ng/mL, identifies the subjects at the highest POAF risk, and with abnormal ECG atrial parameters, such as PW indices, and altered structural heart disease variables. Serum ferritin, RDW, and PTLs represent predictive biomarkers of POAF after cardiothoracic surgery in CECC; particularly, serum ferritin combined with anormal PW indices and structural heart disease variables can represent an optimal tool for predicting not only POAF, but also the eventual stroke onset.

Incidental pseudoaneurysm of the mitral-aortic intervalvular fibrosa in asymptomatic patient: A case report.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) can be a rare but life-threatening complication of infective endocarditis, cardiac surgery, or blunt chest trauma. Congenital heart diseases especially in young patients are reported as additionally predisposing factors. We present the case of an asymptomatic 52 years-old male with bicuspid aortic valve and gastrointestinal polyposis syndrome in whom a P-MAIVF was incidentally detected. The patient successfully underwent pseudoaneurysm surgical repair and aortic valve replacement and despite no evident causes were found we hypothesized addiotional underlying mechanism of P-MAIVF.

Acute thrombotic occlusion of a brachiocephalic branch graft and pseudoaneurysm formation after debranching surgery for a "non-A non-B" aortic dissection.

Non-A non-B aortic dissection is a pathology with potentially life-threatening consequences, and aortic debranching followed by thoracic endovascular aortic repair is one of the possible treatment options. Branch graft occlusion is an infrequent complication and no definite guidelines exist about postoperative antithrombotic therapy nor preoperative evaluation of individual anatomical characteristics-in particular regarding cerebral circulation-in such patients. We present the case of a 54-year-old man undergoing an aortic debranching procedure for a thoracoabdominal aortic dissection originating in the aortic arch, complicated by thrombotic occlusion of the brachiocephalic branch of the prosthesis and pseudoaneurysm of the ascending aorta, with our management and considerations.

Outcome of patients undergoing isolated tricuspid repair or replacement surgery.

OBJECTIVES: The interest in isolated tricuspid valve disease has rapidly increased recently. However, clinical trials and registry data are rare in the surgical literature. This study aimed to describe the early and long-term outcomes of a real-world experience in isolated tricuspid procedures comparing repair and replacement strategies. METHODS: The Surgical-Tricuspid study is a multicentre retrospective study that enrolled adult patients who had undergone isolated tricuspid valve surgery at 13 international sites. Propensity score-matched analysis was used to compare repair versus replacement. RESULTS: A cohort of 426 patients was enrolled [mean age: 55 (16) years; 56% female]. After matching, 175 comparable pairs were analysed. Preoperative left ventricular ejection fraction was 55(9) vs 56(9) (P = 0.8) while moderate-severe tricuspid regurgitation was present in 95% of cases. The 30-day mortality rate was 4.0% vs 8.0% in the repair and replacement groups, respectively (P = 0.115). The rates of re-exploration for bleeding (6.9% vs 13.1% P = 0.050), permanent pacemaker implantation (5.1% vs 12.0%; P = 0.022) and blood transfusion (46% vs 62%; P = 0.002) were higher in the replacement group. Cumulative survival rates at 3, 5 and 7 years in the repair group were 84 (3)%, 75 (4)% and 56 (9)% vs 71 (4)%, 66 (5)% and 58 (5)% in the replacement group (P = 0.001) while cumulative incidence for reoperation at 10 years did not differ between groups [repair 10 (1)% vs replacement 9 (1)%; P = 0.469]. CONCLUSIONS: The data from the Surgical-Tricuspid study reported a high risk for patients undergoing tricuspid surgery. Isolated valve repair offered reduced early and late mortality with no difference regarding reoperation rate when compared with replacement.

The impact of autophagy modulation on phenotype and survival of cardiac stromal cells under metabolic stress.

Cardiac stromal cells (CSCs) embrace multiple phenotypes and are a contributory factor in tissue homeostasis and repair. They can be exploited as therapeutic mediators against cardiac fibrosis and remodeling, but their survival and cardioprotective properties can be decreased by microenvironmental cues. We evaluated the impact of autophagy modulation by different pharmacological/genetic approaches on the viability and phenotype of murine CSCs, which had been subjected to nutrient deprivation or hyperglycemia, in order to mimic relevant stress conditions and risk factors of cardiovascular diseases. Our results show that autophagy is activated in CSCs by nutrient deprivation, and that autophagy induction by trehalose or autophagy-related protein 7 (ATG7)-overexpression can significantly preserve CSC viability. Furthermore, autophagy induction is associated with a higher proportion of primitive, non-activated stem cell antigen 1 (Sca1)-positive cells, and with a reduced fibrotic fraction (positive for the discoidin domain-containing receptor 2, DDR2) in the CSC pool after nutrient deprivation. Hyperglycemia, on the other hand, is associated with reduced autophagic flux in CSCs, and with a significant reduction in primitive Sca1+ cells. Autophagy induction by adenoviral-mediated ATG7-overexpression maintains a cardioprotective, anti-inflammatory and pro-angiogenic paracrine profile of CSCs exposed to hyperglycemia for 1 week. Finally, autophagy induction by ATG7-overexpression during hyperglycemia can significantly preserve cell viability in CSCs, which were subsequently exposed to nutrient deprivation, reducing hyperglycemia-induced impairment of cell resistance to stress. In conclusion, our results show that autophagy stimulation preserves CSC viability and function in response to metabolic stressors, suggesting that it may boost the beneficial functions of CSCs in cardiac repair mechanisms.

Observed versus predicted mortality after isolated tricuspid valve surgery.

BACKGROUND: Aim of this study is to analyse the performances of Clinical Risk Score (CRS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II in isolated tricuspid surgery. METHODS: Three hundred and eighty-three patients (54 ± 16 year; 54% female) were enrolled. Receiver operating characteristic analysis was performed to evaluate the relationship between the true positive fraction of test results and the false-positive fraction for a procedure. RESULTS: Considering the 30-day mortality the area under the curve was 0.6 (95% confidence interval [CI] 0.50-0.72) for EuroSCORE II and 0.7 (95% CI 0.56-0.84) for CRS-score. The ratio of expected/observed mortality showed underestimation when considering EuroSCORE-II (min. 0.46-max. 0.6). At multivariate analysis, the CRS score (p = .005) was predictor of late cardiac death. CONCLUSION: We suggest using both scores to obtain a range of expected mortality. CRS to speculate on late survival.

Functional Tricuspid Regurgitation: Behind the Scenes of a Long-Time Neglected Disease.

Severe tricuspid valve regurgitation has been for a long time a neglected valve disease, which has only recently attracted an increasing interest due to the notable negative impact on the prognosis of patients with cardiovascular disease. It is estimated that around 90% of tricuspid regurgitation is diagnosed as "functional" and mostly secondary to a primary left-sided heart disease and, therefore, has been usually interpreted as a benign condition that did not require a surgical management. Nevertheless, the persistence of severe tricuspid regurgitation after left-sided surgical correction of a valve disease, particularly mitral valve surgery, has been associated to adverse outcomes, worsening of the quality of life, and a significant increase in mortality rate. Similar results have been found when the impact of isolated severe tricuspid regurgitation has been studied. Current knowledge is shifting the "functional" categorization toward a more complex and detailed pathophysiological classification, identifying various phenotypes with completely different etiology, natural history and, potentially, an invasive management. The aim of this review is to offer a comprehensive guide for clinicians and surgeons with a systematic description of "functional" tricuspid regurgitation subtypes, an analysis centered on the effectiveness of existing surgical techniques and a focus on the emergent percutaneous procedures. This latter may be an attractive alternative to a standard surgical approach in patients with high-operative risk or isolated tricuspid regurgitation.

Beating Versus Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes.

BACKGROUND: Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches. METHODS: The Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who underwent isolated TV procedures (n = 406; age 56 ± 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups. RESULTS: After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% ± 6% versus 78% ± 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% ± 5% versus 84% ± 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% ± 9% versus 86% ± 5% (P = .024) comparing AH-TV replacement and BH-TV repair groups. CONCLUSIONS: Isolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome.

Management of Patients With Aortocoronary Saphenous Vein Graft Aneurysms: JACC State-of-the-Art Review.

Saphenous vein graft aneurysms (SVGAs) following coronary artery bypass grafting (CABG) surgery were first described in 1975. Although rare, in the absence of a prompt diagnosis, SVGAs can be responsible for serious complications and adverse outcomes. The clinical presentation of SVGAs described in the literature can vary from an asymptomatic patient with an incidental radiological finding to a profoundly shocked patient with life-threatening hemorrhage secondary to SVGA rupture. Improvements in diagnostic tools within the last decade, such as multislice computed tomographic scanning, has enabled early detection of SVGAs, and therefore, an expansion of the current management options. In this review, the current data and knowledge about clinical presentation, diagnosis, natural history, and treatment of SVGAs are updated, with a specific emphasis on the evolution of management strategies of this rare complication over the last 45 years. Finally, a clinical algorithm to guide decision-making and management is proposed.

Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm.

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) outbreak is a public health emergency affecting different regions around the world. The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection varies from complete absence of symptomatology to more aggressive symptoms, characterized by sudden acute respiratory distress syndrome (ARDS), multiorgan failure, and sepsis, requiring treatment in intensive care unit (ICU). It is not still clear why the immune system is not able to efficiently suppress viral replication in a small percentage of patients. It has been documented as pathological conditions affecting the cardiovascular system, strongly associated to atherosclerotic progression, such as heart failure (HF), coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM), could serve as predictive factors for severity and susceptibility during Sars-CoV-2 infection. Atherosclerotic progression, as a chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory patterns, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1ß. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results reported in severe COVID-19 infections, we hypothesized a pathogenetic correlation. Atherosclerosis may be an ideal pathogenetic substrate for high viral replication ability, leading to adverse outcomes, as reported in patients with cardiovascular factors. The level of atherosclerotic progression may affect a different degree of severe infection; in a vicious circle, feeding itself, Sars-CoV-2 may exacerbate atherosclerotic evolution due to excessive and aberrant plasmatic concentration of cytokines.

Case Report: Emergency CABG Following Failure of PTCA in a COVID-19 Patient.

The coronavirus disease 2019 (COVID-19) pandemic outbreak, caused by severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) is affecting people worldwide representing a public health emergency. The effect of concomitant COVID-19 on patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) is still undefined. Both SARS-Cov-2 infection and CPB can develop a cytokines storm and haemostatic disarrangements leading to acute respiratory distress syndrome (ARDS) and post-perfusion lung syndrome, respectively. SARS-Cov-2 infection may trigger and exacerbate post-inflammatory state after CPB resulting in higher risk of post-surgical adverse outcomes. International guidelines lack to provide standard management protocols for pre-operative COVID-19 patients requiring non-deferrable cardiac surgery intervention. We present a report of a successful coronary artery bypass grafting (CABG) emergency operation in a COVID-19 patient, who presented unstable angina and coronary artery dissection during cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA).

Echocardiography and Correction of Mitral Regurgitation: An Unbreakable Link.

BACKGROUND: Degenerative mitral valve (MV) disease causing mitral regurgitation (MR) is the most common organic valve pathology and is classified based on leaflet motion. MV repair is indicated as the preferred technique (Class I indication) when the results are expected to be durable. Therefore, a detailed and systematic evaluation of MV apparatus is pivotal in allowing the proper surgical planning, as well as the screening for trans catheter-based treatment when surgery is not indicated. AIM: The aim of the present review is to describe the crucial role of both Transthoracic Echocardiography (TTE) and Transesophageal Echocardiography (TEE) in the decisional process and the guidance of MV repair procedures. TTE is the main investigation and the first approach used to make diagnosis of MR, to assess the severity and to describe the underlying mechanism, while TEE, especially with 3D echocardiography, has been shown to be useful for clarifying complicated valvular anatomy, assessing the surgical result and detecting complications. The surgical treatment of MR takes advantage of ultrasound evaluation of MV apparatus at any stage of the process, thus making the link between surgery and echocardiography unbreakable throughout the perioperative phase.

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.