When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) in PRKAG2 Gene Causing Left Ventricular Hypertrophy and Conduction Abnormalities in a Caucasian Patient: Case Report and Literature Review.

PRKAG2 cardiomyopathy is a rare genetic disorder that manifests early in life with an autosomal dominant inheritance pattern. It harbors left ventricular hypertrophy (LVH), ventricular pre-excitation and progressively worsening conduction system defects. Its estimated prevalence among patients with LVH ranges from 0.23 to about 1%, but it is likely an underdiagnosed condition. We report the association of the PRKAG2 missense variant c.1006G>A p. (Val336Ile) with LVH, conduction abnormalities (short PR interval and incomplete right bundle branch bock) and early-onset arterial hypertension (AH) in a 44-year-old Caucasian patient. While cardiac magnetic resonance (CMR) showed a mild hypertrophic phenotype with maximal wall thickness of 17 mm in absence of tissue alterations, the electric phenotype was relevant including brady-tachy syndrome and recurrent syncope. The same variant has been detected in the patient's sister and daughter, with LVH + early-onset AH and electrocardiographic (ECG) alterations + lipothymic episodes, respectively. Paying close attention to the coexistence of LVH and ECG alterations in the proband has been helpful in directing genetic tests to exclude primary cardiomyopathy. Hence, identifying the genetic basis in the patient allowed for familial screening as well as a proper follow-up and therapeutic management of the affected members. A review of the PRKAG2 cardiomyopathy literature is provided alongside the case report.

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.