A patient-specific algorithm to achieve commissural alignment with Acurate Neo: The sextant technique.

AIMS: The aim of this proof-of-concept study was to investigate safety and efficacy of a CT-scan based patient-specific algorithm to maximize coronary clearance and secondarily to achieve anatomically correct commissural alignment with the Acurate Neo device. METHOD AND RESULTS: A total of 45 consecutive patients undergoing TAVR with the Acurate Neo THV were prospectively enrolled in the study. Mean age was 81.6 ± 5.5 years, mean STS score was 6.1 ± 3.7. Device success rate was 100%. Aim of the technique was to rotationally deploy the TAVR device with a commissure lying on the bisector between the coronary ostia as calculated on the pre-procedural CT-scan. At post-TAVR CT-scan, coronary clearance was achieved in 98% of patients with no cases of severe coronary artery overlap. In 42 out of 45 patients, THV was aligned or, at most, mildly misaligned; there were 2 cases of moderate misalignment without any case of severe misalignment. Post-TAVR selective coronary artery engagement was attempted and succeeded in all patients (100%). CONCLUSION: Our CT-scan based patient-specific algorithm is safe and proven to be effective in avoiding coronary artery overlap and providing commissural alignment with Acurate Neo in all treated patients.

Impact of aortic angle on transcatheter aortic valve implantation outcome with Evolut-R, Portico, and Acurate-NEO.

OBJECTIVES: To investigate paravalvular leak (PVL) and devices success rates according to aortic angle (AA) in patients undergoing transcatheter aortic valve implantation (TAVI) with three new-generation self-expanding devices. BACKGROUND: The impact of aortic angle (AA) on TAVI device success and PVL rates is controversial. METHODS: This retrospective study included 392 patients submitted to TAVI for severe aortic stenosis with Portico, Evolut-R and Acurate-NEO, and available AA measurements at computed tomography (CT) angiography. AA was calculated from the implantation projection and was defined as the angle between the plane of aortic annulus and an ideal horizontal plane. Aorta was defined horizontal if AA>57° (75th percentile). RESULTS: In the horizontal group, the rates of moderate/severe PVL was higher in the Evolut-R group (20.8%), which was also characterized by a lower implant compared to that of Acurate-NEO, whereas device success was comparable among the three devices. AA was a significant predictor of moderate/severe PVLs (AUC 0.72, p = .002) only in the Evolut-R population. On multivariate analysis, calcium volume 850HU, bicuspid aortic valve, and implantation depth at the level of left coronary cusp were independent predictors of moderate/severe PVL. On univariate analysis in the horizontal aorta population, implantation depth was confirmed among the most significant predictors of moderate/severe PVL. CONCLUSIONS: Despite comparable device success rates, horizontal aorta represented a technical challenge only in the Evolut-R subgroup, which showed higher rates of moderate/severe PVL than Portico and Acurate-NEO, and was associated with a low implant.

Diagnosis of left atrial appendage thrombus in patients with atrial fibrillation: delayed contrast-enhanced cardiac CT.

OBJECTIVES: The current reference standard for diagnosing LAA thrombi is transesophageal echocardiography (TEE), a semi-invasive technique. We aimed to devise an optimal protocol for cardiac computed tomography (CCT) in diagnosing left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF), using TEE as reference standard. METHODS: Two hundred sixty consecutive patients referred for radiofrequency ablation for AF were prospectively enrolled. All patients underwent CCT and TEE within 2 hours. The CCT protocol included one standard angiographic phase and three delayed acquisitions at 1-, 3-, and 6-min after contrast injection. Thrombi were defined as persisting defects at 6-min delayed acquisition. RESULTS: TEE demonstrated spontaneous contrast in 52 (20%) patients and thrombus in 10 (4%). In 63 patients (24%), CCT demonstrated LAA early filling defects at angiographic phase. Among them, 15 (6%) had a persistent defect at 1-min, 12 (5%) at 3-min, and 10 (4%) at 6-min. All 10 thrombi diagnosed on TEE were correctly identified by delayed CCT, without any false positives. For all phases, sensitivity and negative predictive were 100%. Specificity increased from 79% for the angiographic phase to 100% at 6-min. Positive predictive value increased from 16% to 100%. Estimated radiation exposure was 2.08 ± 0.76 mSv (mean ± standard deviation) for the angiographic phase and 0.45 ± 0.23 mSv for each delayed phase. CONCLUSION: A CCT protocol adding a 6-min delayed phase to the angiographic phase can be considered optimized for the diagnosis of LAA thrombi, with a low radiation dose. KEY POINTS: • In patients with persistent atrial fibrillation referred for ablation procedures, a cardiac CT examination comprising an angiographic-phase acquisition and, in case of filling defects, a 6-min delayed phase may help reduce the need for transesophageal echocardiography. • Cardiac CT would provide morphological and volumetric data, along with the potential to exclude the presence of thrombi in the left atrial appendage.

Dual-energy CT performance in acute pulmonary embolism: a meta-analysis.

OBJECTIVES: To evaluate the diagnostic performance of dual-energy computed tomography (DECT) with regard to its post-processing techniques, namely linear blending (LB), iodine maps (IM), and virtual monoenergetic (VM) reconstructions, in diagnosing acute pulmonary embolism (PE). METHODS: This meta-analysis was conducted according to PRISMA. A systematic search on MEDLINE and EMBASE was performed in December 2019, looking for articles reporting the diagnostic performance of DECT on a per-patient level. Diagnostic performance meta-analyses were conducted grouping study parts according to DECT post-processing methods. Correlations between radiation or contrast dose and publication year were appraised. RESULTS: Seventeen studies entered the analysis. Only lobar and segmental acute PE were considered, subsegmental acute PE being excluded from analysis due to data heterogeneity or lack of data. LB alone was assessed in 6 study parts accounting for 348 patients, showing a pooled sensitivity of 0.87 and pooled specificity of 0.93. LB and IM together were assessed in 14 study parts accounting for 1007 patients, with a pooled sensitivity of 0.89 and pooled specificity of 0.90. LB, IM, and VM together were assessed in 2 studies (for a total 144 patients) and showed a pooled sensitivity of 0.90 and pooled specificity of 0.90. The area under the curve for LB alone, and LB together with IM was 0.93 (not available for studies using LB, IM and VM because of paucity of data). Radiation and contrast dose did not decrease with increasing year of publication. CONCLUSIONS: Considering the published performance of single-energy CT in diagnosing acute PE, either dual-energy or single-energy computed tomography can be comparably used for the detection of acute PE. KEY POINTS: • Dual-energy CT displayed pooled sensitivity and specificity of 0.87 and 0.93 for linear blending alone, 0.89 and 0.90 for linear blending and iodine maps, and 0.90 and 0.90 for linear blending iodine maps, and virtual monoenergetic reconstructions. • The performance of dual-energy CT for patient management is not superior to that reported in literature for single-energy CT (0.83 sensitivity and 0.96 specificity). • Dual-energy CT did not yield substantial advantages in the identification of patients with acute pulmonary embolism compared to single-energy techniques.

Transarterial Endoleak Closure After Endovascular Thoracoabdominal Aneurysm Repair: When the "Sandwich" Goes Wrong.

PURPOSE: To describe the use of vascular plugs to close a complex type Ib endoleak following the sandwich procedure used in conjunction with endovascular thoracoabdominal aortic aneurysm (TAAA) repair. CASE REPORT: A 59-year-old man with a 6.5-mm TAAA was treated with initial deployment proximally of 2 Zenith TX2 stent-grafts. In preparation for the sandwich technique to preserve flow to the celiac trunk, a 10×100-mm Viabahn covered stent was delivered from a brachial access into the celiac trunk unprotected by the sheath of the introducer. The trigger wire system became snagged on the struts of the distal aortic stent-graft; when the wire was pulled, the proximal end of the Viabahn migrated outside the aortic stent-graft, which migrated upward. The main body extension intended for the aortic component of the sandwich technique was deployed close to the distal end of the aneurysm sac, but a large type Ib endoleak formed in the gutter between the Viabahn, aortic extension, and sac wall. The leak perfused the celiac trunk, and the procedure was terminated. Increasing sac size on 3-month imaging prompted closure of the leak with 2 type II Amplatzer vascular plugs aiming to occlude the endoleak outflow into the Viabahn and the endoleak outflow at the site of the gutter. Imaging follow-up at 6 months demonstrated successful exclusion of the TAAA with no residual endoleak and excellent perfusion of the celiac trunk. CONCLUSION: Transarterial treatment of complex endoleaks is feasible when preceded by meticulous imaging and detailed preprocedural planning.

Transfemoral Treatment of a Paraprosthetic Mitral Leak and Mitral Bioprosthesis Failure Complicated by Embolization of In-Situ Vascular Plug.

Today, increasing numbers of patients are presenting to clinical teams with signs and symptoms of mitral bioprosthesis failure. Whilst redo surgery is currently the treatment option of choice, many patients have multiple co-morbidities and are deemed to be of prohibitively high surgical and anaesthetic risk. Percutaneous transcatheter treatment can offer a potential solution for these patients. Herein is reported a case where simultaneous transcatheter interventions for paraprosthetic leak and mitral bioprosthesis implantation were performed via the transfemoral route, and an unforeseen complication was successfully managed.

Semaglutide therapy decreases epicardial fat inflammation and improves psoriasis severity in patients affected by abdominal obesity and type-2 diabetes.

Summary: Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was -80 HU and PCAT attenuation of the right coronary artery (RCA) was -68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient's life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient's quality of life, compared with baseline. Learning points: Psoriasis patients affected by obesity and type-2 diabetes (T2D) are often resistant to biologic therapies. Psoriasis is often associated with abdominal obesity, T2D, and cardiovascular diseases (CVD), given their shared inflammatory properties and pathogenic similarities. Epicardial adipose tissue (EAT) inflammation can cause the distinctive pattern of CVD seen in psoriasis. EAT and pericoronary adipose tissue (PCAT) attenuation, assessed by routine coronary computed tomography angiography (CCTA), can be used as biomarkers of inflammation and allow monitoring of medical anti-inflammatory therapies. The actions of semaglutide to reduce energy intake, improve glycemic control, and produce effective weight loss, particularly at the visceral fat depot level, can diminish adipose tissue dysfunction, reduce EAT attenuation and PCAT attenuation of the right coronary artery (RCA) and concomitantly ameliorate the clinical severity of psoriasis. Semaglutide therapy may be considered in psoriasis patients affected by T2D and abdominal obesity, despite low cardiovascular risk by traditional risk scores, who are resistant to biologic therapies.

Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies.

AIMS: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein-coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). METHODS AND RESULTS: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). CONCLUSIONS: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-protein­coupled receptors may produce beneficial cardiovascular and metabolic effects.

Transcatheter vs surgical aortic valve replacement in intermediate-surgical-risk patients with aortic stenosis: a propensity score-matched case-control study.

BACKGROUND: Limited real-world data comparing outcomes after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in intermediate-surgical-risk patients with aortic stenosis are available. METHODS: We identified 182 consecutive patients who underwent TAVR via the transfemoral (TF) route (November 2007-February 2011) and 111 moderate-to-high-risk historical case controls undergoing SAVR (August 2003-July 2008). Using propensity score matching based on clinical characteristics and surgical risk scores, we compared clinical outcomes in 111 matched patients. Valve Academic Research Consortium definitions were applied for end point adjudication. RESULTS: Baseline clinical characteristics, in particular Logistic European System for Cardiac Operative Risk Evaluation (23.2 ± 15.1 vs 24.4 ± 13.4) and Society of Thoracic Surgeons score (4.6 ± 2.3 vs 4.6 ± 2.6), were well matched between groups. Transfemoral TAVR was associated with more vascular complications (33.3% vs 0.9%, P < .001). On the other hand, acute kidney injury was more frequent after SAVR (8.1% vs 26.1%, P < .001). The rates of all-cause mortality in both TF-TAVR and SAVR groups was1.8% at 30 days (P = 1.00) and 6.4% and 8.1%, respectively, at 1 year (P = .80). At 1 year, the rate of cerebrovascular events was similar in the 2 groups (4.6% vs 9.1%, P = .19). CONCLUSIONS: In this real-world cohort of intermediate-surgical-risk patients with aortic stenosis, TF-TAVR and SAVR were associated with similar mortality rates during follow-up but with a different spectrum of periprocedural complications. Furthermore, the survival rate after TF-TAVR in this group of elderly patients with intermediate Society of Thoracic Surgeons score was encouraging.

[Spontaneous resolution of pericardial cyst: a complex case report]. / Scomparsa spontanea di cisti pericardica: descrizione di un caso clinico intricato.

Pericardial cysts are rare mediastinal abnormalities, generally benign, discovered most often incidentally in the course of diagnostic investigations involving the cardiac profile. They have an incidence of 1 case in 100 000 and are mostly located at the right cardiophrenic angle. Spontaneous resolution of cysts is even rarer. We describe an intricate case report in which the cyst was discovered incidentally and was no longer detected at cardiac magnetic resonance performed 7 years after the first diagnosis. The presence of an asymptomatic pericardial cyst should be regularly followed up over time for the potential risks of complications related to its growth but also because over time, although rarely, it may no longer be detected as in the case presented.

Pulmonary thromboembolism in coronavirus disease 2019 patients undergoing thromboprophylaxis.

ABSTRACT: We aimed to investigate the prevalence of pulmonary thromboembolism (PTE) and its association with clinical variables in a cohort of hospitalized coronavirus disease 2019 (COVID-19) patients receiving low-molecular-weight heparin (LMWH) at prophylactic dosage.In this retrospective observational study we included COVID-19 patients receiving prophylactic LMWH from admission but still referred for lower-limbs venous Doppler ultrasound (LL-US) and computed tomography pulmonary angiography (CTPA) for clinical PTE suspicion. A dedicated radiologist reviewed CTPA images to assess PTE presence/extension.From March 1 to April 30, 2020, 45 patients were included (34 men, median age 67 years, interquartile range [IQR] 60-76). Twenty-seven (60%) had PTE signs at CTPA, 17/27 (63%) with bilateral involvement, none with main branch PTE. In 33/45 patients (73%) patients LL-US was performed before CTPA, with 3 patients having superficial vein thrombosis (9%, none with CTPA-confirmed PTE) and 1 patient having deep vein thrombosis (3%, with CTPA-confirmed PTE). Thirty-three patients (73%) had at least one comorbidity, mainly hypertension (23/45, 51%) and cardiovascular disease (15/45, 33%). Before CTPA, 5 patients had high D-dimer (11.21 µg/mL, IQR 9.10-13.02), 19 high fibrinogen (550 mg/dL, IQR 476-590), 26 high interleukin-6 (79 pg/mL, IQR 31-282), and 11 high C-reactive protein (9.60 mg/dL, IQR 6.75-10.65), C-reactive protein being the only laboratory parameter significantly differing between patients with and without PTE (P = .002)High PTE incidence (60%) in COVID-19 hospitalized patients under prophylactic LMWH could substantiate further tailoring of anticoagulation therapy.

Potential role of epicardial adipose tissue as a biomarker of anthracycline cardiotoxicity.

BACKGROUND: We investigated the radiodensity of epicardial (EAT), subcutaneous (SAT), and visceral adipose tissue (VAT) before and after treatment with anthracyclines in a population of breast cancer (BC) patients, and in controls not treated with anthracyclines, to detect a potential role of EAT density as a biomarker of changes related to chemotherapy cardiotoxicity. METHODS: We reviewed BC patients treated with anthracyclines who underwent CT before (CT-t0) and after (CT-t1) chemotherapy, and age- and sex-matched controls who underwent two CT examinations at comparable intervals. On non-contrast scans, EAT was segmented contouring the pericardium and thresholding between -190 and -30 Hounsfield units (HU), and SAT and VAT were segmented with two 15-mm diameter regions of interest thresholded between -195 and -45 HU. RESULTS: Thirty-two female patients and 32 controls were included. There were no differences in age (p = 0.439) and follow-up duration (p = 0.162) between patients and controls. Between CT-t0 and CT-t1, EAT density decreased in BC patients (-66 HU, interquartile range [IQR] -71 to -63 HU, to -71 HU, IQR -75 to -66 HU, p = 0.003), while it did not vary in controls (p = 0.955). SAT density increased from CT-t0 to CT-t1 in BC patients (-107 HU, IQR -111 to -105 HU, to -105 HU, IQR -110 to -100 HU, p = 0.014), whereas it did not change in controls (p = 0.477). VAT density did not vary in either BC patients (p = 0.911) or controls (p = 0.627). CONCLUSIONS: EAT density appears to be influenced by anthracycline treatment for BC, well known for its cardiotoxicity, shifting towards lower values indicative of a less active metabolism.

CT-derived pulmonary vascular metrics and clinical outcome in COVID-19 patients.

To assess pulmonary vascular metrics on chest CT of COVID-19 patients, and their correlation with pneumonia extent (PnE) and outcome, we analyzed COVID-19 patients with an available previous chest CT, excluding those performed for cardiovascular disease. From February 21 to March 21, 2020, of 672 suspected COVID-19 patients from two centers who underwent CT, 45 RT-PCR-positives (28 males, median age 75, IQR 66-81 years) with previous CTs performed a median 36 months before (IQR 12-72 months) were included. We assessed PnE, pulmonary artery (PA) diameter, ascending aorta (Ao) diameter, and PA/Ao ratio. Most common presentations were fever and dyspnea (15/45) and fever alone (13/45). Outcome was available for 41/45 patients, 15/41 dead and 26/41 discharged. Ground-glass opacities (GGOs) alone were found in 29/45 patients, GGOs with consolidations in 15/45, consolidations alone in 1/45. All but one patient had bilateral pneumonia, 9/45 minimal, 22/45 mild, 9/45 moderate, and 5/45 severe PnE. PA diameter (median 31 mm, IQR 28-33 mm) was larger than before (26 mm, IQR 25-29 mm) (P<0.001), PA/Ao ratio (median 0.83, IQR 0.76-0.92) was higher than before (0.76, IQR 0.72-0.82) (P<0.001). Patients with adverse outcome (death) had higher PA diameter (P=0.001), compared to discharged ones. Only weak correlations were found between ΔPA or ΔPA/Ao and PnE (ρ≤0.453, P≤0.032), with 4/45 cases with moderate-severe PnE and minimal increase in PA metrics. In conclusion, enlarged PA diameter was associated to death in COVID-19 patients, a finding deserving further investigation as a potential driver of therapy decision-making.

Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization.

BACKGROUND AND AIMS: Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization. METHODS AND RESULTS: Sixty-four patients (aged 69 ± 8 years, 45% females) with carotid stenosis <70% based on Doppler flow velocity were enrolled in the study. Potential causes of cerebral damage other than atherosclerosis, including history of atrial fibrillation, heart failure, previous cardiac or neurosurgery and neurological disorders were excluded. All subjects underwent carotid computed tomography angiography, contrast enhanced ultrasound for assessment of plaque neovascularization and brain magnetic resonance imaging for measuring brain volumes. On multivariate regression analysis, age and fibrocalcific plaques were independently associated with lower total brain volumes (ß = -3.13 and ß = -30.7, both p < 0.05). Fibrocalcific plaques were also independently associated with lower gray matter (GM) volumes (ß = -28.6, p = 0.003). On the other hand, age and extent of carotid atherosclerosis were independent predictors of lower white matter (WM) volumes. CONCLUSIONS: WM and GM have different susceptibility to processes involved in parenchymal loss. Contrary to common belief, our results show that presence of fibrocalcific plaques is associated with brain atrophy.

First-in-Man Study Evaluating the Emblok Embolic Protection System During Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to evaluate the feasibility of complete cerebral protection during transcatheter aortic valve replacement (TAVR) with a novel embolic protection device. BACKGROUND: Evidences and data about new cerebral embolic protection devices are lacking and scarce. METHODS: A prospective, nonrandomized, multicenter, first-in-man pilot study designed to evaluate the efficacy and safety of cerebral embolic protection utilizing the Emblok embolic protection system (Innovative Cardiovascular Solutions, Grand Rapids, Michigan) during TAVR. The Emblok is a transfemoral aortic filter that provide full coverage of the epiaortic vessels. Brain diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at baseline and 2 to 5 days after TAVR. Primary endpoints were technical success and immediate cerebral embolic burden after TAVR, defined as number and volume of new brain lesions detected with DW-MRI at days 2 to 5 post-TAVR compared with baseline. RESULTS: A total of 20 subjects were enrolled. The Emblok system was successfully positioned in all the cases. At 30-day follow-up, no major adverse cardiovascular and cerebrovascular events occurred. Nineteen (95%) patients had new ischemic defects at post-procedural DW-MRI. The median number of new lesions per patient was 10.00 (interquartile range [IQR]: 4.75 to 15.25). The total new lesion volume was 199.9 mm3 (IQR: 83.9 to 447.5 mm3) and the mean lesion volume per lesion was 42.5 mm3 (IQR: 21.5 to 75.6 mm3). Histopathologic analysis showed evidence of significant debris in 18 (90%) filters. CONCLUSIONS: The Emblok embolic protection system appears to be feasible and safe during TAVR. The device was successfully placed and retrieved in all cases and no neurological events were observed. Cerebral total new lesion volume was similar to other trials on cerebral protection during TAVR, thus warranting a larger study. (European Study Evaluating the Emblok Embolic Protection System During TAVR; NCT03130491).

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization.

BACKGROUND AND AIMS: Brain white matter hyperintensities (WMHs) have been associated with an increased risk of ischemic stroke and considered as markers of brain ischemia. Progression of WMHs in asymptomatic patients with non-hemodynamically significant carotid plaque could represent a putative marker of plaque vulnerability. We prospectively evaluate progression and determinants of WMHs in this population. METHODS: This prospective study included 51 asymptomatic patients with carotid stenosis <70% that underwent brain magnetic resonance imaging scans at baseline and after a median follow up of 595 days (interquartile range 553-641 days). Patients (mean age of 69 years and 45% females) underwent baseline carotid computed tomography angiography, contrast-enhanced ultrasound for carotid plaque characterization and analysis of subsets of circulating lymphocytes and monocytes by flow cytometry. RESULTS: Seventeen subjects (33.3%) had carotid stenoses of 50-70% (Doppler flow velocity) while the rest had stenoses of <50%. In 25 (49.0%) patients, new WMHs, with 5 new lesions on average and a median volume of 134 mm3, were detected at follow-up. None of the plaque characteristics or of the circulating cellular biomarkers investigated were associated with the global and ipsilateral occurrence of new WMHs whereas, at multivariate analysis, female sex, hypercholesterolemia, and lower glomerular filtration rate (GFR) emerged as independent variables associated with new WMHs. CONCLUSIONS: Half of the patients with carotid plaques of intermediate severity had evidence of WMH progression at follow up. Female gender and systemic factors such as hypercholesterolemia, and lower GFR, but not plaque characteristics or circulating cellular biomarkers, are associated with WMH progression.

Carotid artery plaque uptake of 11C-PK11195 inversely correlates with circulating monocytes and classical CD14++CD16- monocytes expressing HLA-DR.

BACKGROUND: We explored the relation between blood concentrations of monocyte/lymphocyte subsets and carotid artery plaque macrophage content, measured by positron emission tomography (PET) with 11C-PK11195. METHODS AND RESULTS: In 9 patients with carotid plaques we performed 11C-PK11195-PET/computed tomography angiography imaging and measurement of absolute concentrations and frequencies of circulating monocytes and T-cell subsets. Plaque standardized uptake value (SUV) for 11C-PK11195 was negatively correlated with concentrations of total monocytes (r = -0.58, p = 0.05) and CD14++CD16-HLA-DR+ classical subset (r = -0.82, p = 0.005). These correlations hold true also in relation to plaque target to background ratio. No correlation was observed between plaque SUV and CD3+T lymphocytes, CD4+T lymphocytes nor with activated CD3+CD4+T cells expressing HLA-DR. CONCLUSIONS: We first demonstrated a reduction in the absolute concentration of monocytes and particularly in classical monocytes expressing HLA-DR in the presence of an increased uptake of 11C-PK11195 in carotid plaques. The present work, despite being a pilot study comprising only a small number of subjects provides new insights in the search for specific cellular biomarkers with potential diagnostic and prognostic value in patients with a known carotid plaque.