Endothelial Progenitor Cells: An Appraisal of Relevant Data from Bench to Bedside.

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.

Left ventricular stiffness predicts outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: Assessment of the prognostic role of left ventricular stiffness (LVS) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: We performed a complete two-dimensional transthoracic echocardiographic study before and after TAVI in patients with severe AS at high surgical risk. In order to assess LVS, we measured LV end-diastolic pressure (EDP) invasively during TAVI and LV end-diastolic volume (EDV) by means of echocardiography. We defined LVS as the EDV indexed by body surface area at an EDP of 20 mm Hg (EDVI20 ). Our aim was to assess the impact of LVS on one-year all-cause mortality after TAVI. RESULTS: One hundred sixty-six patients undergoing TAVI (64% female; mean age 82.7 ± 5.1 years) were enrolled. Seven patients died within the first 30 days after TAVI and 21 within 1 year. Overall follow-up duration was 580 ± 478 days. At multivariate analysis, independent predictors of 1-year all-cause mortality were moderate-to-severe paravalvular leak (PVL; HR 4.7, 95% confidence interval [CI] 1.9-11, P=.0003), female gender (HR 3.5, 95% CI 1.0-12, P=.045), and EDVI20 (HR 0.94, 95% CI 0.90-0.98, P=.015). In particular, patients with higher LVS (EDVI20 ≤48 mL/m2 ) had a 1-year mortality of 26.9% vs 7.4% in patients with lower LVS (EDVI20 >48 mL/m2 ; HR 4.2, 95% CI 1.6-10.6, P=.0007). Patients with higher LVS who developed moderate-to-severe PVL had the worst outcome (incremental chi-square test, P=.014). CONCLUSION: In patients with AS, an increased LVS has a negative prognostic impact. Development of significant PVL in patients with higher LVS had an incremental adverse effect.

Evolving Paradigms in Transcatheter Aortic Valve Replacement: Results from a High-Volume, Single Center Experience.

Given the expanding indications toward younger patients at lower surgical risk, transcatheter aortic valve replacement (TAVR) simplification and streamlining are gaining increasing importance. Patients who underwent TAVR from the year 2015 to 2020 were prospectively enrolled. The patients were divided in time tertiles according to the date of intervention. Data on preprocedural planning, including coronary computed tomography angiography (CCTA), procedures, and outcomes, were compared between the time tertiles. A total of 771 consecutive patients from a single institution were enrolled. We observed a trend toward the use of a fully percutaneous versus surgical approach for the index access, left radial artery versus contralateral femoral artery for the secondary access, and left ventricular pacing on the stiff guidewire versus right ventricular pacing. Immediate device success significantly increased, whereas the length of hospital stay decreased. Overall, approximately 60% of the total study population underwent CCTA instead of coronary angiography, with no adverse events. One-year survival rates significantly improved over time. A simplified TAVR approach was associated with better survival, whereas low baseline functional capacity, preexisting coronary artery disease, renal impairment, periprocedural blood transfusions, and paravalvular leak were related to worse outcomes. In conclusion, our study showed a constant tendency to procedure streamlining and improve procedural success and 1-year outcomes. A strategy based on CCTA allows sparing safely almost half of the preoperative invasive coronary angiography.

Heterotopic Transcatheter Tricuspid Valve Replacement in Severe Tricuspid Regurgitation and Refractory Right Heart Failure.

Torrential tricuspid regurgitation may lead to heart failure and poor survival and quality of life. Heterotopic transcatheter tricuspid replacement is increasingly offered to patients unsuitable for direct valve repair or replacement. We describe 1 patient treated by transcatheter implantation of 2 self-expanding valves in the venae cavae with a multimodality imaging approach. (Level of Difficulty: Advanced.).

Transcatheter aortic valve replacement with or without anesthesiologist: results from a high-volume single center.

AIMS: Local instead of general anesthesia has become the standard approach in many centers for transfemoral transcatheter aortic valve replacement (TAVR). New generation devices and an increase in operator skills had led to a drastic reduction in periprocedural complications, bringing in the adoption of a minimalist approach. In our study, we aimed to compare patients treated with TAVR under local anesthesia with or without the presence of an anesthesiologist on site (AOS). METHODS: We compare procedural aspects and results of patients treated with TAVR with an AOS against patients treated with TAVR with an anesthesiologist on call (AOC). From January 2019 to December 2020, all consecutive patients undergoing transfemoral TAVR with either the self-expandable Evolut (Medtronic, MN, USA) or balloon-expandable SAPIEN 3 (Edwards Lifesciences, CA, USA) were collected. RESULTS: Of 332 patients collected, 96 (29%) were treated with TAVR with AOS, while 236 (71%) were treated with TAVR with AOC. No differences in procedural time, fluoroscopy time and amount of contrast medium were observed. No procedural death and conversion to open-chest surgery was reported. The rate of stroke/transient ischemic attacks and major vascular complications was similar in the two groups. No patients in both groups required conversion to general anesthesia. Two patients (0.8%) in the AOC group required urgent intervention of the anesthesiologist. In the AOC group, there was a greater use of morphine (55.9% vs. 33.3%, P  = 0.008), but with a lower dose for each patient (2.0 vs. 2.8 mg, P  = 0.006). On the other hand, there was a lower use of other painkiller drugs (3.4% vs. 20.8%, P  = 0.001). No difference in inotropic drugs use was observed. CONCLUSION: In patients at low or intermediate risk undergoing transfemoral TAVR, a safe procedure can be performed under local anesthesia without the presence of an anesthesiologist in the catheterization laboratory.

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated type 1 diabetes.

BACKGROUND: Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated. METHODS: Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured. RESULTS: After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 µm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP. CONCLUSIONS: Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.

[Asymptomatic Takayasu's arteritis: an incidental diagnosis]. / Arterite asintomatica di Takayasu: una diagnosi occasionale.

We present the case of a 56 years-old female patient that was admitted to our Unit after an incidental observation of bilateral absence of the radial pulses, with impossibility of brachial arterial pressure measurement. The patient reported being completely asymptomatic in occasion of the episode, thus like previously and later on to it. We diagnosed the patient being affected of Takayasu arteritis and adeguate therapy had been undertaken.

Threshold for calcium volume evaluation in patients with aortic valve stenosis: correlation with Agatston score.

BACKGROUND: The evaluation of aortic valve calcium burden is important when planning for transcatheter aortic valve implantation (TAVI). Although a robust golden standard methodology is available for calcium evaluation on noncontrast-enhanced (NCE) computed tomographic (CT) series, a standard reference for calcium assessment on contrast-enhanced CT series is currently lacking. METHODS: Two hundred and forty-four preprocedural CT scans from patients who had received TAVI were analysed. We correlated the aortic calcium volumes obtained on CE series at three thresholds [450, 850, and 'probe + 100' Hounsfield Units (HU)] with the Agatston score obtained on NCE scans. A subgroup analysis was performed taking into account the contrast enhancement of the left ventricular outflow tract (LVOT), with a prespecified cut-off of 300 HU. RESULTS: The overall population analysis showed higher correlation with the Agatston score using the 850 HU threshold (r = 0.45, P < 0.0001); no correlation was found with the 450 HU threshold, whilst the 'probe + 100' HU threshold showed a weaker correlation (r = 0.30, P < 0.0001). In patients with LVOT enhancement less than 300 HU, 450 HU showed the highest accuracy in calcium identification (r = 0.70, P < 0.0001), whereas in patients with LVOT enhancement of at least 300 HU, the most accurate threshold was 850 HU (r = 0.46, P < 0.0001). CONCLUSION: The thresholds for correct calcium identification using the automatic 3Mensio software depend on the contrast enhancement of aortic and cardiac structures, which can be estimated by measuring the HU in the LVOT. In patients with LVOT HU of less than 300, the correct threshold to be set in the software is 450 HU, whereas in patients with LVOT HU of at least 300 the correct threshold is 850 HU.

COAPT-Like Profile Predicts Long-Term Outcomes in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation.

OBJECTIVES: The aim of this study was to evaluate whether fulfilling COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) criteria identifies patients with better outcomes after MitraClip treatment for secondary mitral regurgitation (SMR). BACKGROUND: To date, COAPT is the only trial showing a prognostic benefit of MitraClip implantation compared with conservative management. METHODS: Three hundred four patients with SMR undergoing MitraClip placement in addition to optimal medical therapy at 3 European centers were analyzed. A COAPT-like profile was defined as absence of all the following criteria: severe left ventricular impairment, moderate to severe right ventricular dysfunction, severe tricuspid regurgitation, severe pulmonary hypertension, and hemodynamic instability. Freedom from all-cause death and from a composite endpoint (cardiovascular death and heart failure hospitalization) were evaluated at 2- and 5-year follow-up. RESULTS: A COAPT-like profile was observed in 65% of the population. Compared with non-COAPT-like patients, those fulfilling COAPT criteria had greater survival free from all-cause death and from the composite endpoint at both 2 year (75% vs. 55% and 67% vs. 47%; p < 0.001 for both) and 5-year (49% vs. 25% and 40% vs. 19%; p < 0.001 for both) follow-up. Among the non-COAPT-like patients, similar outcomes were observed in those fulfilling 1 or ≥1 criterion. Left ventricular impairment had a late impact on outcomes, while right ventricular impairment, pulmonary hypertension, and hemodynamic instability had early effects. COAPT-like profile was an independent predictor of long-term outcomes, as well as administration of neurohormonal antagonists, European System for Cardiac Operative Risk Evaluation II score, and previous heart failure hospitalization. CONCLUSIONS: A COAPT-like profile, including specific echocardiographic and clinical criteria, identifies patients with SMR who have a better prognosis after MitraClip implantation.

In situ formation of Au-Pd bimetallic active sites promoting the physically mixed monometallic catalysts in the liquid-phase oxidation of alcohols.

The catalytic oxidation of alcohols with molecular oxygen on supported nanometallic catalysts represents one of the green methods in a crucial process for the synthesis of fine chemicals. We have designed an experiment using physically mixed Au/AC and Pd/AC (AC=activated carbon) as the catalyst in the liquid-phase oxidation of benzyl alcohol by aerobic oxygen. The evolution of the physically mixed catalyst structures at different stages in the catalytic reaction was investigated by aberration-corrected high-resolution transmission electron microscopy and spatially resolved element mapping techniques at the nanometre scale, and they were also compared with the structure of the bimetallic alloy. For the first time we show the formation of surface Au-Pd bimetallic sites by reprecipitation of Pd onto Au nanoparticles. Negligible Au leaching was observed. The in situ structural evolution can be directly correlated to the great enhancement of the catalyst activity. Moreover, we distinguish the different behaviours of Au and Pd, thus suggesting an oxygen differentiating mechanism for Au and Pd sites. The findings are of great importance to both the understanding of the structure-activity correlation and the design of highly active catalysts in green chemistry.

Long-term results and durability of the CoreValve transcatheter aortic bioprosthesis: outcomes beyond five years.

AIMS: The aim of this study was to determine the long-term outcomes of high-risk patients who underwent transcatheter aortic valve implantation (TAVI) with the third-generation CoreValve device, according to the 2017 EAPCI/ESC/EACTS definition of valve durability. METHODS AND RESULTS: Between 2007 and 2013, 278 consecutive patients were enrolled in our prospective single-centre CoreValve registry (mean age 82±6 years, mean STS score 6.4±5.0%). The median follow-up of survivors was 6.8 years. The Cox proportional hazards model was used to identify independent predictors of HF rehospitalisation and all-cause mortality. Predictors of HF rehospitalisation were LVEF, MR and PVL at the last echocardiographic follow-up. The majority of patients were in NYHA Class I or II and showed mild/trivial paravalvular leak throughout follow-up. Mean pressure gradients remained stable over time. The overall crude cumulative incidences of structural valve deterioration and bioprosthetic valve failure were 3.6% and 2.5%, respectively. CONCLUSIONS: Although overall mortality was high in this elderly patient cohort, the CoreValve bioprosthesis showed good durability at seven-year follow-up.

Preprocedural planning of transcatheter mitral valve interventions by multidetector CT: What the radiologist needs to know.

Mitral regurgitation is the most common valve disorder in the Western world, and although surgery is the established therapeutic gold standard, percutaneous transcatheter mitral interventions are gaining acceptance in selected patients who are inoperable or at an exceedingly high surgical risk. For such patients, multidetector computed tomography (MDCT) can provide a wealth of valuable morphological and functional information in the preoperative setting. Our aim is to give an overview of the MDCT image acquisition protocols, post-processing techniques, and imaging findings with which radiologists should be familiar to convey all relevant information to the Heart Team for successful treatment planning.

A meta-analysis of MitraClip combined with medical therapy vs. medical therapy alone for treatment of mitral regurgitation in heart failure patients.

AIMS: Survival benefit of percutaneous mitral valve repair with the MitraClip over conservative treatment of functional mitral regurgitation (MR) remains unclear. The purpose of this meta-analysis is to compare survival outcomes of MitraClip with those of medical therapy in patients with functional MR. METHODS AND RESULTS: A comprehensive literature search of PubMed, MEDLINE, and Google Scholar was conducted including studies evaluating MitraClip vs. medical therapy with multivariate adjustment and with >80% of patients with functional MR. Death from any cause was the primary endpoint, while freedom from readmission was the secondary one, evaluated with random effects. These analyses were performed at study level and at patient level including only functional MR when available, evaluating the effect of MitraClip in different subgroups according to age, ischaemic aetiology, presence of implantable cardioverter defibrillator/cardiac resynchronization therapy, and left ventricular ejection fraction and volumes. We identified six eligible observational studies including 2121 participants who were treated with MitraClip (n = 833) or conservative therapy (n = 1288). Clinical follow-up was documented at a median of 400 days. At study-level analysis, MitraClip, when compared with medical therapy (P = 0.005), was associated with significant reduction of death (P = 0.002) and of readmission due to cardiac disease. At patient-level analysis, including 344 patients, MitraClip confirmed robust survival benefit over medical therapy for all patients with functional MR and among the most important subgroups. CONCLUSIONS: Compared with conservative treatment, MitraClip is associated with a significant survival benefit. Importantly, this superiority is particularly pronounced among patients with functional MR and across all the main subgroups.

Effects of levosimendan in patients with severe functional mitral regurgitation undergoing MitraClip implantation.

AIM: Percutaneous mitral valve repair (PMVR) with a MitraClip device has been recently introduced as a valuable therapy in high surgical risk patients with functional mitral regurgitation (FMR) who are not responding to currently available medical treatments. Our aim was to assess the clinical, functional and prognostic impact of periprocedural levosimendan administration in patients with end-stage heart failure and FMR undergoing PMVR. METHODS: Between December 2009 and August 2016, 94 consecutive high-risk patients with symptomatic FMR who underwent PMVR with the MitraClip System at our center were enrolled in a prospective registry. To identify two comparable groups of patients, 27 patients receiving levosimendan (No-L-group) were selected for the analysis matching by propensity score with those not treated with levosimendan (L-group). RESULTS: Baseline demographics and echocardiographic variables were similar between the two groups. Acute procedural success was similarly high in both groups with no significant differences in procedural time and hospital outcomes. At discharge, echocardiographic parameters did not differ among groups except for higher value of right ventricle tissue Doppler imaging peak systolic-wave velocity in the L-group (10.7 versus 13.0 cm/s, P = 0.03, respectively). There was no significant difference in 1-year mortality between patients receiving levosimendan and those not treated with levosimendan. CONCLUSION: Prophylactic levosimendan did not affect long-term outcome in patients undergoing PMVR. However, levosimendan as an adjunctive therapy to MitraClip implantation offers further therapeutic advantages in patients with advanced heart failure by improving systolic right ventricle function.

Tailored N-Containing Carbons as Catalyst Supports in Alcohol Oxidation.

The introduction of N-containing functionalities in carbon-based materials is brought to stable and highly active metal-supported catalysts. However, up to now, the role of the amount and the nature of N-groups have not been completely clear. This study aims to clarify these aspects by preparing tailored N-containing carbons where different N-groups are introduced during the synthesis of the carbon material. These materials were used as the support for Pd nanoparticles. Testing these catalysts in alcohol oxidations and comparing the results with those obtained using Pd nanoparticles supported on different N-containing supports allowed us to obtain insight into the role of the different N-containing groups. In the cinnamyl alcohol oxidation, pyridine-like groups seem to favor both activity and selectivity toward cinnamaldehyde.

Comparison of Percutaneous Mitral Valve Repair Versus Conservative Treatment in Severe Functional Mitral Regurgitation.

Percutaneous mitral valve repair (PMVR) using the MitraClip System is feasible and entails clinical improvement even in patients with high surgical risk and severe functional mitral regurgitation (MR). The aim of this study was to assess survival rates and clinical outcome of patients with severe, functional MR treated with optimal medical therapy (OMT) compared with those who received MitraClip device. Sixty patients treated with OMT were compared with a propensity-matched cohort of 60 patients who underwent PMVR. Baseline demographics and echocardiographic variables were similar between the 2 groups. The mean age of patients was 75 years, and 67% were men. The median logistic EuroSCORE and EuroSCORE II were 17% and 6%, respectively, because of the presence of several co-morbidities. The mechanism of MR was functional in all cases with an ischemic etiology in 52% of patients. Median left ventricle ejection fraction was 34%. All the patients were symptomatic for dyspnea with 63% and 12% in the New York Heart Association class III and IV, respectively. In PMVR group, the procedure was associated with safety and very low incidence of procedural complications with no occurrence of procedural and inhospital mortality. After a median follow-up of 515 days (248 to 828 days), patients treated with PMVR demonstrated overall survival, survival freedom from cardiac death and survival free of readmission due to cardiac disease curves higher than patients treated conservatively (log-rank test p = 0.007, p = 0.002, and p = 0.04, respectively). In conclusion, PMVR offers a valid option for selected patients with high surgical risk and severe, functional MR and entails better survival outcomes compared with OMT.

Noninvasive Transcutaneous Monitoring in Long-Term Follow-Up of Patients With Thromboangiitis Obliterans Treated With Intravenous Iloprost.

We evaluated the effectiveness of intravenous iloprost (IVI) in outpatients with thromboangiitis obliterans (TAO) and lower limb noninvasive transcutaneous monitoring (TCM) at follow-up (FU). Ten consecutive patients with TAO underwent IVI therapy. Transcutaneous oxygen (TcPo 2) and carbon dioxide (TcPco 2) determination and laser Doppler flowmetry (LDF) were performed before and after IVI at 3, 6, and 12 months of FU. Clinical response was positive in 7 patients, whereas 3 nonresponders underwent a second IVI cycle with 1 showing a late positive clinical response. After 12 months of FU, all patients were alive without amputations. Supine and dependent TcP2 levels significantly improved (P < .005). Hallux LDF values showed significant change with the maximal hyperemic test at 44°C (P < .005). Forefoot maximal hyperemic test at 44°C LDF (P < .005) and improved venous arterial reflex (P < .05) showed statistically significant time evolution. We demonstrated some degree of IVI effectiveness and evaluated TCM in patients with TAO.

Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients.

BACKGROUND: By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD). PATIENTS: This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded. METHODS: CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median. RESULTS: The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index. CONCLUSION: The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement.