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.

[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.

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.

[Saphenous vein graft aneurysm: percutaneous exclusion using detachable coils]. / Aneurisma del graft venoso: esclusione percutanea mediante l'uso di spirali.

We report the case of a 78-year-old man admitted to the emergency department for typical angina onset with evidence of a large aneurysm of the coronary artery venous bypass graft, successfully closed using a percutaneous approach.

Five-year evolution of mild aortic regurgitation following transcatheter aortic valve implantation: early insights from a single-centre experience.

OBJECTIVES: To assess the follow-up evolution and impact of mild aortic regurgitation (1 + AR) following transcatheter aortic valve implantation (TAVI). METHODS: We evaluated the follow-up outcomes and AR evolution of 558 patients affected by native aortic stenosis who underwent TAVI with residual AR ≤ 1+. RESULTS: No residual AR was found in 294 (52.7%) patients, whereas 1 + AR was found in 264 (47.3%) patients. At 5.5 years, freedom from all-cause mortality (56.9% vs 53.5%), cardiac mortality (75.0% vs 74.3%) and heart failure (70.0% vs 63.9%) were similar between no-AR and 1 + AR groups, respectively (all P > 0.05). New York Heart Association Class I-II was found in 88.9% vs 82.4% of patients respectively ( P = 0.013). Freedom from AR ≥3+ at 5.5 years was 98.6% in the no-AR group vs 82.5% in the 1 + AR group (log-rank <0.001). Residual 1 + AR was found to be an independent predictor of increased follow-up AR ≥3+ ( P = 0.012). In 1 + AR group, higher left ventricle mass index independently predicted increased cardiac death [hazards ratio (HR) 1.01, confidence interval (CI) 1.00-1.02, P = 0.036] and heart failure rate (HR 1.01, CI 1.00-1.02, P = 0.002), while larger native aortic annulus perimeter predicted follow-up AR ≥ 3+ (HR 1.12, CI 1.02-1.22, P = 0.016). CONCLUSIONS: 5 years after TAVI, a higher progression of paravalvular AR to Grade ≥3+ together with worse symptoms were found in patients with residual 1 + AR compared with no-AR, although no marked difference in survival was observed. These findings raise further concerns about 1+ residual AR after TAVI, especially in the perspective of expanding indications to younger low-risk patients. Mechanisms that cause progression of paravalvular AR after TAVI remain to be clarified.

Feasibility of ultra-low contrast 64-slice computed tomography angiography before transcatheter aortic valve implantation: a real-world experience.

AIMS: To investigate the feasibility, image quality, and clinical implications of an ultra-low-dose contrast injection computed tomography angiography (CTA) protocol in patients scheduled for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Images obtained with 64-slice CT were retrospectively evaluated in 162 TAVI candidates with a body mass index (BMI) of ≤29 kg/m(2). A multiphasic, low iodine dose and BMI-adapted CM protocol was administered in all patients (BMI <22 kg/m(2): 40 mL; BMI 22-29 kg/m(2): 55 mL). All images were evaluated for image quality, vessel attenuation, and estimated radiation dose. The anatomy, diameters, perimeter, and area of the aortic annulus were assessed. Anatomy and diameters of peripheral vessels were also evaluated. Image quality of the aortic root and ilio-femoral vessels was diagnostic in all patients. Vascular attenuation was >200 HU at any vessel level. The mean diameters of the aortic annulus were 22 ± 3 mm (range: 16-28 mm) × 26 ± 3 mm (range: 20-33 mm); the mean perimeter was 77.0 ± 7.1 mm. After CTA, a total of 137 patients (84.6%) underwent TAVI. Mean estimated radiation dose was 20.2 ± 4.6 mSv. CONCLUSION: With our protocol, we achieved images of the aortic annulus and aorto-iliac anatomy of sufficient quality to allow patient selection and procedural planning for TAVI, with a substantial reduction of the amount of injected CM.

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.

Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis.

OBJECTIVE: TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI. DESIGN: All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance. PATIENTS: A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean/peak gradients (54.5 ± 12.2/88 ± 19.5 mm Hg), LVEF (21%=EF ≤ 40%), sPAP (43.1 ± 11.6 mmHg). INTERVENTIONS: All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%). MAIN OUTCOME MEASURES: Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%. RESULTS: At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p<0.001), decreased sPAP (43.1 ± 11.6 mm Hg vs 37.1 ± 7.7 mm Hg; p<0.001) and increased LVEF in those with EF ≤ 40% (34.9 ± 6% vs 43.5 ± 14.4%; p=0.006). Concerning QOL, 49% walked unassisted, 79% (39.5% among pts ≥ 85 years) reported self-awareness improvement; QOL was reported as "good" in 58% (31.4% among pts ≥ 85 years), "acceptable according to age" in 34% (16% among pts ≥ 85 years) and "bad" in 8%. CONCLUSION: TAVI procedures improve clinical outcome and subjective health-related QOL in very elderly patients with symptomatic AS.

Image quality and radiation exposure with prospectively ECG-triggered axial scanning for coronary CT angiography: the multicenter, multivendor, randomized PROTECTION-III study.

OBJECTIVES: The purpose of this study was to evaluate image quality and radiation dose using a prospectively electrocardiogram (ECG)-triggered axial scan protocol compared with standard retrospective ECG-gated helical scanning for coronary computed tomography angiography. BACKGROUND: Concerns have been raised regarding radiation exposure during coronary computed tomography angiography. Although the use of prospectively ECG-triggered axial scan protocols may effectively lower radiation dose compared with helical scanning, it is unknown whether image quality is maintained in a clinical setting. METHODS: In a prospective, multicenter, multivendor trial, 400 patients with low and stable heart rates were randomized to either an axial or a helical coronary computed tomography angiography scan protocol. The primary endpoint was to demonstrate noninferiority in image quality with the axial scan protocol, which was assessed on a 4-point scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints included radiation dose and the rate of downstream testing during 30-day follow-up. RESULTS: Image quality in patients scanned with the axial scan protocol (score 3.36 ± 0.59) was not inferior compared with helical scan protocols (3.37 ± 0.59) (p for noninferiority <0.004). Axial scanning was associated with a 69% reduction in radiation exposure (dose-length product [estimated effective dose] 252 ± 147 mGy · cm [3.5 ± 2.1 mSv] vs. 802 ± 419 mGy · cm [11.2 ± 5.9 mSv] for axial vs. helical scan protocols, p < 0.001). The rate of downstream testing did not differ (13.8% vs. 15.9% for axial vs. helical scan protocols, p = 0.555). CONCLUSIONS: In patients with stable and low heart rates, the prospectively ECG-triggered axial scan protocol maintained image quality but reduced radiation exposure by 69% compared with helical scanning. Axial computed tomography data acquisition should be strongly recommended in suitable patients to avoid unnecessarily high radiation exposure.

Percutaneous valve replacement in a young adult for radiation-induced aortic stenosis.

A 46-year-old woman known with relapsing Hodgkin's lymphoma diagnosed at age 5, treated with repeated cycles of radiotherapy and chemotherapy, presented with severe symptomatic radiation-induced aortic stenosis. She also had other late sequelae of radiotherapy including thyroid cancer, mediastinal fribrosis and left pulmonary fibrosis with severe restrictive lung disease and a newly diagnosed renal carcinoma. Due to the prohibitively high surgical risk and need for urgent treatment, she underwent successful transcatheter aortic valve replacement with transfemoral implantation of a 23 mm Edwards SAPIEN-XT prosthesis, which was performed without valvuloplasty of the noncalcified fibrotic valve. The final result was excellent with reduction of the transaortic gradient and no residual aortic regurgitation.

Transcatheter valve-in-valve implantation with the Edwards SAPIEN in patients with bioprosthetic heart valve failure: the Milan experience.

AIMS: Reoperation for bioprosthetic heart valve failure is associated with significant morbidity and mortality, particularly in high-risk patients. Transcatheter valve-in-valve (VIV) implantation may offer a less invasive alternative. The aim of this study was to report our initial experience with transcatheter VIV implantation to treat degenerated tissue valves. METHODS AND RESULTS: VIV implantation with the Edwards SAPIEN transcatheter heart valve (THV; Edwards Lifesciences Inc, Irvine, CA, USA) was performed in 18 high-risk patients (STS 8.2±5.2%; logistic EuroSCORE 37.4±20.8%) with symptomatic bioprosthetic failure (17 aortic, one mitral). Valve Academic Research Consortium (VARC) definitions were applied for endpoint adjudication. Transfemoral access was the preferred vascular approach (16 patients, with the mitral VIV delivered anterogradely through the femoral vein; one transaxillary and one transapical). The majority (83%) of procedures were performed under local anaesthesia and sedation. Device success was achieved in all but one patient who had a final transaortic gradient ≥20mmHg. Acute kidney injury occurred in three patients (Stage 3 in 1), life-threatening or major bleeding in four patients, while major vascular complications occurred in one patient. Permanent pacemaker implantation was required in two patients. There were no deaths or neurological events at 30-day follow-up. At a median follow-up of 11 months (interquartile range 6-16), the mortality rate was 5.6% and all patients were in NYHA class II or lower. CONCLUSIONS: Transcatheter implantation of the Edwards THV within a degenerated aortic bioprosthesis, performed predominantly via the transfemoral route, is feasible and associated with good periprocedural and clinical outcomes in high-risk surgical patients.

[Multimodality imaging in transcatheter aortic valve implantation procedures: the pivotal role of echocardiography]. / L'imaging multimodale nell'impianto transcatetere della valvola aortica: il ruolo fondamentale dell'ecocardiografia.

Alternative percutaneous approaches to the management of symptomatic aortic stenosis in elderly and high-risk patients have become more attractive and raised profound interest in recent years. The superiority of transcatheter aortic valve implantation (TAVI) compared with medical therapy for patients deemed unsuitable for surgery has recently been established by the PARTNER trial, and preliminary randomized data in high-risk patients have confirmed that TAVI is non-inferior to surgical valve replacement in terms of safety and effectiveness. This finding will probably lead to an exponential increase in TAVI procedures over the next decade. In the clinical setting of the percutaneous approach, the choice of a specific valve is crucial to optimize the success rate and minimize the procedure-related complications and requires accurate preprocedural diagnostic assessment. According to the high comorbidities of candidates currently undergoing a TAVI procedure, a tailored diagnostic framework in the elderly population is highly recommended. The present review discusses the role of echocardiography in the setting of multimodality imaging before the TAVI procedure and throughout the entire process, from patient selection to procedural guidance and post-procedural follow-up, suggesting a practical algorithm necessary for the best clinical outcome.