Physical preconditioning on biventricular temporary mechanical circulatory support while awaiting heart transplantation.

Temporary mechanical circulatory support (tMCS) is increasingly used in patients with cardiogenic shock as a bridge to further treatment. We present the case of a 52-year-old female patient with biventricular heart failure who was bridged to heart transplantation employing biventricular tMCS through a non-femoral access. The 'groin-free' tMCS concept facilitates pre-habilitation while awaiting heart transplantation.

Mediastinal transposition of the greater omentum for treatment of infected prostheses of the ascending aorta and aortic arch.

OBJECTIVES: The aim of this study was to evaluate the outcomes of transposition of the omentum into the mediastinum to support the replacement of infected aortic grafts or to cover infected aortic grafts that are not amenable for surgical replacement. METHODS: All patients with thoracic aortic graft infections who underwent mediastinal transposition of the omentum at our institution between 2005 and 2023 were included in this study. Mediastinal transposition of the omentum was performed either after replacement of the infected graft ('curative concept') or solely as bailout procedure by wrapping the infected graft ('palliative concept'). The diagnosis, including computed tomography scans during follow-up, was made according to the criteria of the Management of Aortic Graft Infection Collaboration. RESULTS: The patient cohort consisted of 31 patients. Both in-hospital and 1-year mortality were 0% (n = 0) for the curative concept (n = 9) compared to 23% (n = 5) and 41% (n = 9) for the palliative concept (n = 22), respectively. There was no graft infection-associated death or recurrence of infection after 3 years in the curative group. Survival was 52% at 3 years in the palliative group, with freedom of infection in 59% of the patients (n = 13). CONCLUSIONS: Transposition of the omentum and wrapping of the infected aortic prosthetic graft is a useful bailout strategy for patients who are ineligible for replacement of an infected aortic graft. However, mortality stays high. For radical treatment of aortic graft infections, it may prove an effective supportive therapy and represents an important tool in the armamentarium of cardiac surgeons.

Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.

CD40L-CD40-TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L-CD40-TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L-CD40-TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L-CD40-TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view.

Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia-reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

The role of ex-situ perfusion for thoracic organs.

PURPOSE OF REVIEW: Ex-situ machine perfusion for both heart (HTx) and lung transplantation (LuTx) reduces ischemia-reperfusion injury (IRI), allows for greater flexibility in geographical donor management, continuous monitoring, organ assessment for extended evaluation, and potential reconditioning of marginal organs. In this review, we will delineate the impact of machine perfusion, characterize novel opportunities, and outline potential challenges lying ahead to improve further implementation. RECENT FINDINGS: Due to the success of several randomized controlled trials (RCT), comparing cold storage to machine perfusion in HTx and LuTx, implementation and innovation continues. Indeed, it represents a promising interface for organ-specific therapies targeting IRI, allo-immune responses, and graft reconditioning. These mostly experimental efforts range from genetic approaches and nanotechnology to cellular therapies, involving mesenchymal stem cell application. Despite tremendous potential, prior to clinical transition, more data is needed. SUMMARY: Collectively, machine perfusion constitutes the vanguard in thoracic organ transplantation research with extensive potential for expanding the donor pool, enhancing transplant outcomes as well as developing novel therapy approaches.

Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium.

Background: Although the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan started a new era in heart failure (HF) treatment, less is known about the tissue-level effects of the drug on the atrial myocardial functional reserve and arrhythmogenesis. Methods and Results: Right atrial (RA) biopsies were retrieved from patients (n = 42) undergoing open-heart surgery, and functional experiments were conducted in muscle strips (n = 101). B-type natriuretic peptide (BNP) did not modulate systolic developed force in human myocardium during ß-adrenergic stimulation, but it significantly reduced diastolic tension (p < 0.01) and the probability of arrhythmias (p < 0.01). In addition, patient's plasma NTproBNP positively correlated with isoproterenol-induced contractile reserve in atrial tissue in vitro (r = 0.65; p < 0.01). Sacubitrilat+valsartan (Sac/Val) did not show positive inotropic effects on atrial trabeculae function but reduced arrhythmogeneity. Atrial and ventricular biopsies from patients with end-stage HF (n = 10) confirmed that neprilysin (NEP) is equally expressed in human atrial and ventricular myocardium. RA NEP expression correlates positively with RA ejection fraction (EF) (r = 0.806; p < 0.05) and left ventricle (LV) NEP correlates inversely with left atrial (LA) volume (r = -0.691; p < 0.05). Conclusion: BNP ameliorates diastolic tension during adrenergic stress in human atrial myocardium and may have positive long-term effects on the inotropic reserve. BNP and Sac/Val reduce atrial arrhythmogeneity during adrenergic stress in vitro. Myocardial NEP expression is downregulated with declining myocardial function, suggesting a compensatory mechanism in HF.

Predictive Value of Two-Dimensional Speckle-Tracking Echocardiography in Patients Undergoing Surgical Ventricular Restoration.

Objectives: Parameters of left ventricular (LV) mechanics, obtained from speckle-tracking echocardiography (STE), were found to be of prognostic value in patients with heart failure and those who underwent cardiac surgery. This study aimed to assess the value of STE in patients scheduled to undergo surgical ventricular restoration (SVR). Methods: A total of 158 consecutive patients with baseline STE who underwent SVR due to an LV anteroapical aneurysm were included in the analysis. Preoperative longitudinal STE parameters were evaluated for their association with an outcome, defined as all-cause mortality, LV assist device implantation, or heart transplantation. The echocardiographic follow-up to assess the change in the regional function of the segments remote from the aneurysm was performed in 43 patients at a median of 10 months [interquartile range (IQR): 6-12.7 months] after SVR. Results: During a median follow-up of 5.1 years (IQR: 1.6-8.7 years), events occurred in 68 patients (48%). Less impaired mean basal end-systolic longitudinal strain (BLS) with a cutoff value ≤ -10.1 % demonstrated a strong association with event-free survival, also in patients with an LV shape corresponding to an intermediate shape between aneurysmal and globally akinetic. Initially hypo- or akinetic basal segments with preoperative end-systolic strain ≤ -7.8% showed a greater improvement in wall motion at the short-term follow up. Conclusion: Patients with less impaired preoperative BLS exhibited a better event-free survival after SVR, also those with severe LV remodeling. The preserved preoperative segmental longitudinal strain was associated with a greater improvement in regional wall motion after SVR. BLS assessment may play a predictive role in patients with an LV anteroapical aneurysm who are scheduled to undergo SVR.

Surgical Restoration of Antero-Apical Left Ventricular Aneurysms: Cardiac Computed Tomography for Therapy Planning.

Background: Surgical ventricular restoration (SVR) leads to functional improvement by volume reduction and restoration of left ventricular (LV) geometry. Our purpose was to refine the planning for SVR using cardiac computed tomography (CCT). Methods: The possibility to anticipate the postoperative residual LV volume was assessed using CCT in 205 patients undergoing SVR combined with coronary artery bypass grafting (77%), mitral valve repair/replacement (19%) and LV thrombectomy (19%). The potential of CCT to guide the procedure was evaluated. Additionally, the predictive value of CCT characteristics on survival was addressed. Results: 30-day, 1- and 5-year survival was 92.6, 82.7, and 72.1%, respectively, with a marked reduction of NYHA class III-IV quota after surgery (95.1% vs. 20.5% in the follow-up). Both pre- and postoperative LV end-systolic volume index (LVESVI) were predictive of all defined endpoints according to the following tertiles: preoperative: <74 ml/m2, 74-114 ml/m2 and >114 ml/m2; postoperative: <58 ml/m2, 58-82 ml/m2 and >82 ml/m2. On average, a 50 ml/m2 increase of preoperative LVESVI was associated with a 35% higher hazard of death (p = 0.043). Aneurysms limited to seven antero-apical segments (1-7) were associated with a lower death risk (n = 60, HR 0.52, CI 0.28-0.96, p = 0.038). LVESVI predicted by CCT was found to correlate significantly with effectively achieved LVESVI (r = 0.87 and r = 0.88, respectively, p < 0.0001). Conclusions: CCT-guided SVR can be performed with good mid-term survival and significant improvement in HF severity. CCT-based assessment of achievable postoperative LV volume helps estimate the probability of therapeutic success in individual patients.

A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats.

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common form of PH, yet its pathophysiology is poorly characterized than pulmonary arterial hypertension (PAH). As a result, approved therapeutic interventions for the treatment or prevention of PH-LHD are missing. Medications used to treat PH in PAH patients are not recommended for treatment of PH-LHD, as reduced pulmonary vascular resistance (PVR) and increased pulmonary blood flow in the presence of increased left-sided filling pressures may cause left heart decompensation and pulmonary edema. New strategies need to be developed to reverse PH in LHD patients. In contrast to PAH, PH-LHD develops due to increased mechanical load caused by congestion of blood into the lung circulation during left heart failure. Clinically, mechanical unloading of the left ventricle (LV) by aortic valve replacement in aortic stenosis patients or by implantation of LV assist devices in end-stage heart failure patients normalizes not only pulmonary arterial and right ventricular (RV) pressures but also PVR, thus providing indirect evidence for reverse remodeling in the pulmonary vasculature. Using an established rat model of PH-LHD due to left heart failure triggered by pressure overload with subsequent development of PH, a model is developed to study the molecular and cellular mechanisms of this physiological reverse remodeling process. Specifically, an aortic debanding surgery was performed, which resulted in reverse remodeling of the LV myocardium and its unloading. In parallel, complete normalization of RV systolic pressure and significant but incomplete reversal of RV hypertrophy was detectable. This model may present a valuable tool to study the mechanisms of physiological reverse remodeling in the pulmonary circulation and the RV, aiming to develop therapeutic strategies for treating PH-LHD and other forms of PH.

Prognostic impact of secondary prevention after coronary artery bypass grafting-insights from the TiCAB trial.

OBJECTIVES: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG. METHODS: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing. RESULTS: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]. CONCLUSIONS: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months.

Travelling with heart failure: risk assessment and practical recommendations.

Patients with heart failure are at a higher risk of cardiovascular events compared with the general population, particularly during domestic or international travel. Patients with heart failure should adhere to specific recommendations during travel to lower their risk of developing heart failure symptoms. In this Review, we aim to provide clinicians with a set of guidelines for patients with heart failure embarking on national or international travel. Considerations when choosing a travel destination include travel distance and time, the season upon arrival, air pollution levels, jet lag and altitude level because all these factors can increase the risk of symptom development in patients with heart failure. In particular, volume depletion is of major concern while travelling given that it can contribute to worsening heart failure symptoms. Pre-travel risk assessment should be performed by a clinician 4-6 weeks before departure, and patients should receive advice on potential travel-related illness and on strategies to prevent volume depletion. Oxygen supplementation might be useful for patients who are very symptomatic. Upon arrival at the destination, potential drug-induced photosensitivity (particularly in tropical destinations) and risks associated with the local cuisine require consideration. Special recommendations are needed for patients with cardiac implantable electronic devices or left ventricular assist devices as well as for those who have undergone major cardiac surgery.

Surgical Ventricular Reconstruction Eligible for Late Assist Device Implantation.

In patients with ischemic cardiomyopathy and left ventricular aneurysm formation who are symptomatic despite optimal medical therapy, it is challenging to determine whether surgical ventricular reconstruction, heart transplantation, or left ventricular assist device (LVAD) implantation is the treatment of choice. This report describes the concept of surgical ventricular reconstruction with a specially prepared LVAD fixation ring to facilitate subsequent LVAD implantation if required. In the patient reported in this case, endoventricular circular LVAD ring plasty sufficiently reduced the ventricular volume, normalized the left ventricular geometry, and subsequently led to an improvement of left ventricular ejection fraction.

Impact of Muscle Mass as a Prognostic Factor for Failed Waiting Time Prior to Heart Transplantation.

Objectives: Clinical deterioration during the waiting time impairs the prognosis of patients listed for heart transplantation. Reduced muscle mass increases the risk for mortality after cardiac surgery, but its impact on resilience against deterioration during the waiting time remains unclear. Methods: We retrospectively analyzed data from 93 patients without a VAD who were listed in Eurotransplant status "high urgent (HU)" for heart transplantation between January 2015 and October 2020. The axial muscle area of the erector spinae muscles at the level of thoracic vertebra 12 indexed to body surface area (TMESA/BSA) measured in the preoperative thoracic computed tomography scan was used to measure muscle mass. Results: Forty patients (43%) underwent emergency VAD implantation during the waiting time and four patients (4%) died during the waiting time. The risk of emergency VAD implantation/death during the waiting time decreased by 10% for every cm2/m2 increase in muscle area [OR 0.901 (95% CI: 0.808-0.996); p = 0.049]. After adjusting for gender [OR 0.318 (95% CI: 0.087-1.073); p = 0.072], mean pulmonary artery pressure [OR 1.061 (95% CI: 0.999-1.131); p = 0.060], C-reactive protein [OR 1.352 (95% CI: 0.986-2.027); p = 0.096], and hemoglobin [OR 0.862 (95% CI: 0.618-1.177); p = 0.360], TMESA/BSA [OR 0.815 (95% CI: 0.698-0.936); p = 0.006] remained an independent risk factor for emergency VAD implantation/death during the HU waiting time. Conclusion: Muscle area of the erector spinae muscle appears to be a potential, easily identifiable risk factor for emergency VAD implantation or death in patients on the HU waiting list for heart transplantation. Identifying patients at risk could help optimize the outcome and the timing of VAD support.

Impaired Relaxation and Reduced Lusitropic Reserve in Atrial Myocardium in the Obese Patients.

Background: Obesity can influence the structure and function of the atrium, but most studies focused on the relationship of body mass index (BMI) and overt left atrium (LA) dysfunction as assessed by clinical imaging. We combined the assessment of right atrium (RA) function in vivo and in vitro in obese and non-obese patients scheduled for elective cardiac surgery. Methods: Atrial structure and function were quantified pre-operatively by echocardiography. RA tissue removed for the establishment of extracorporeal support was collected and RA trabeculae function was quantified in vitro at baseline and with adrenergic stimulation (isoproterenol). Fatty acid-binding protein 3 (FABP3) was quantified in RA tissue. Results were stratified according to the BMI of the patients. Results: About 76 patients were included pre-operatively for the echocardiographic analysis. RA trabeculae function at baseline was finally quantified from 46 patients and RA function in 28 patients was also assessed with isoproterenol. There was no significant correlation between BMI and the parameters of atrial function measured by the clinical echocardiography. However, in vitro measurements revealed a significant correlation between BMI and a prolonged relaxation of the atrial myocardium at baseline, which persisted after controlling for the atrial fibrillation and diabetes by the partial correlation analysis. Acceleration of relaxation with isoproterenol was significantly lower in the obese group (BMI ≥ 30 kg/m2). As a result, relaxation with adrenergic stimulation in the obese group remained significantly higher compared to the overweight group (25 kg/m2 ≤ BMI < 30 kg/m2, p = 0.027) and normal group (18.5 kg/m2 ≤ BMI < 25 kg/m2, p = 0.036). There were no differences on impacts of the isoproterenol on (systolic) developed force between groups. The expression of FABP3 in the obese group was significantly higher compared to the normal group (p = 0.049) and the correlation analysis showed the significant correlations between the level of FABP3 in the RA trabeculae function. Conclusion: A higher BMI is associated with the early subclinical changes of RA myocardial function with the slowed relaxation and reduced adrenergic lusitropy.

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R).

AIM: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. METHODS AND RESULTS: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. CONCLUSION: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Development of tricuspid regurgitation and right ventricular performance after implantation of centrifugal left ventricular assist devices.

BACKGROUND: Tricuspid regurgitation (TR) after left ventricular assist device (LVAD) implantation is associated with a poor prognosis. This study evaluates the development of TR and right ventricular (RV) performance after LVAD implantation. METHODS: Retrospective analysis of patients who underwent LVAD implantation between March 2018 and June 2019. Patients who underwent concomitant tricuspid valve surgery and patients with congenital heart disease were excluded. RESULTS: A total of 155 patients underwent LVAD implantation. Fourteen patients were excluded. Of the remaining patients, thirty-one died during the first six months, six were lost to follow-up and two underwent transplantation. 102 patients presented at 6.3 months (5.8 to 7.0). Patients were supported with HeartWare HVAD (74%) or HeartMate 3 (26%). 50.4% were rated as INTERMACS profile 1 or 2. At six months, systolic pulmonary artery pressure dropped from 36 to 21 mmHg (P<0.001). Tricuspid annular plane systolic excursion decreased from 17.3 to 14.3 mm (P<0.001), RV fractional area change did not change (P=0.839). Twenty-two patients (22%) presented with moderate-to-severe or severe (ms-s) TR pre-operatively. Of these, eighteen (81%) showed improvement to ≤ moderate TR. At follow-up twelve patients presented with ms-s TR. Of these, only four patients (33%) had been diagnosed with ms-s TR pre-operatively. There were no differences in pre-operative echocardiographic or clinical parameters between the twelve patients with ms-s late TR and the other ninety patients in the cohort. CONCLUSIONS: TR can show an impressive improvement with LVAD support. Longitudinal RV function decreases; this appears to be compensated by transverse shortening. Late TR can develop independently from pre-operative parameters including TR.

Promyelocytic leukemia protein promotes the phenotypic switch of smooth muscle cells in atherosclerotic plaques of human coronary arteries.

Promyelocytic leukemia protein (PML) is a constitutive component of PML nuclear bodies (PML-NBs), which function as stress-regulated SUMOylation factories. Since PML can also act as a regulator of the inflammatory and fibroproliferative responses characteristic of atherosclerosis, we investigated whether PML is implicated in this disease. Immunoblotting, ELISA and immunohistochemistry showed a stronger expression of PML in segments of human atherosclerotic coronary arteries and sections compared with non-atherosclerotic ones. In particular, PML was concentrated in PML-NBs from α-smooth muscle actin (α-SMA)-immunoreactive cells in plaque areas. To identify possible functional consequences of PML-accumulation in this cell type, differentiated human coronary artery smooth muscle cells (dHCASMCs) were transfected with a vector containing the intact PML-gene. These PML-transfected dHCASMCs showed higher levels of small ubiquitin-like modifier (SUMO)-1-dependent SUMOylated proteins, but lower levels of markers for smooth muscle cell (SMC) differentiation and revealed more proliferation and migration activities than dHCASMCs transfected with the vector lacking a specific gene insert or with the vector containing a mutated PML-gene coding for a PML-form without SUMOylation activity. When dHCASMCs were incubated with different cytokines, higher PML-levels were observed only after interferon γ (IFN-γ) stimulation, while the expression of differentiation markers was lower. However, these phenotypic changes were not observed in dHCASMCs treated with small interfering RNA (siRNA) suppressing PML-expression prior to IFN-γ stimulation. Taken together, our results imply that PML is a previously unknown functional factor in the molecular cascades associated with the pathogenesis of atherosclerosis and is positioned in vascular SMCs (VSMCs) between upstream IFN-γ activation and downstream SUMOylation.

Validity of visual assessment of aortic valve morphology in patients with aortic stenosis using two-dimensional echocardiography.

The diagnostic value of a visual assessment of aortic valve (AV) morphology for grading aortic stenosis (AS) remains unclear. A visual score (VS) for assessing the AV was developed and its reliability with respect to Doppler measurements and the calcium score (ctCS) derived by multislice computed tomography was evaluated. 99 Patients with AS of various severity and 38 patients without AS were included in the analysis. Echocardiographic studies were evaluated using the new VS which includes echogenicity, thickening, localization of lesions and leaflet mobility, with a total score ranging from 0 to 11. The association of VS with ctCS and the severity of AS was analyzed. There was a significant correlation of VS with AV hemodynamic parameters and with ctCS. The cut-off value for the detection of AS of any grade was a VS of 6 (sensitivity 95%, specificity 85% for women; sensitivity 85%, specificity 88% for men). A VS of 9 for women and of 10 for men was able to predict severe AS with a high specificity (96% in women and 94% in men, AUC 0.8 and 0.86, respectively). The same cut-off values were identified for the detection of ctCS of ≥ 1600 AU and ≥ 3000 AU with a specificity of 77% and 82% (AUC 0.69 and 0.81, respectively). Assessment of aortic valve morphology can serve as an additional diagnostic tool for the detection of AS and an estimation of its severity.