Coexistence of bicuspid aortic valve, aberrant right subclavian artery and common origin of carotid arteries.

BACKGROUND: Prevalence of bicuspid aortic valve (BAV) and right aberrant sub-clavian artery (ASA) separately is relatively common in general population, and much higher in some disorders. Surprisingly, coexistence of both valve and vessel anomalies has only been reported in single cases. MATERIALS AND METHODS: From 2008 to 2016, in a single, high-volume tertiary cardiac centre, patients who underwent chest computed tomography (CT) for various reasons, were retrospectively screened for the presence of right ASA. RESULTS: Seventy-two patients with either right or left ASA were identified by CT. Among them 7 cases of BAV and right ASA coexistence were identified. Additionally, 1 case with coexisting common origin of carotid arteries (COCA) was visualised in this subgroup. CONCLUSIONS: Although coexistence of ASA and BAV has not been reported in paediatric population, it has been diagnosed in very few adults as well as in our series. Additional presence of COCA in this group seems to be very rare. From practical point of view, heart cannulation via the radial artery and subsequent ASA may be challenging. Similarly, COCA presence may have surgical implications during corrective procedures.

The clinical utility of circulating neuroendocrine gene transcript analysis in well-differentiated paragangliomas and pheochromocytomas.

CONTEXT: Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. OBJECTIVE: To evaluate whether a 51-neuroendocrine gene blood analysis has clinical utility as a diagnostic and prognostic marker. DESIGN: Prospective cohort study. Well-differentiated PPGLs (n = 32), metastatic (n = 4); SDHx mutation (n = 25); 12 biochemically active, Lanreotide treated (n = 4). Nine patients had multiple sampling. Age- and gender-matched controls and GEP-NETs (comparators). METHODS: Circulating neuroendocrine tumor mRNA measured (qPCR) with multianalyte algorithmic analysis. Metabolic, epigenomic and proliferative genes as well as somatostatin receptor expression were assessed (averaged, normalized gene expression: mean ± s.e.m.). Amines were measured by HPLC and chromogranin A by ELISA. Analyses (2-tailed): Fisher's test, non-parametric (Mann-Whitney), receiver-operator curve (ROC) and multivariate analysis (MVA). All data are presented as mean ± s.e.m. RESULTS: PPGL were NETest positive (100%). All exhibited higher scores than controls (55 ± 5% vs 8 ± 1%, P = 0.0001), similar to GEP-NETs (47 ± 5%). ROC analysis area under curve was 0.98 for differentiating PPGLs/controls (cut-off for normal: 26.7%). Mutation status was not directly linked to NETest. Genetic and molecular clustering was associated (P < 0.04) with NETest scores. Metastatic (80 ± 9%) and multicentric (64 ± 9%) disease had significantly (P < 0.04) higher scores than localized disease (43 ± 7%). Progressive disease (PD) had the highest scores (86 ± 2%) vs stable (SD, 41 ± 2%) (P < 0.0001). The area under the curve for PD from SD was 0.93 (cut-off for PD: 53%). Proliferation, epigenetic and somatostatin receptor gene expression was elevated (P < 0.03) in PD. Metabolic gene expression was decreased in SDHx mutations. Repeat NETest measurements defined clinical status in the 9 patients (6 SD and 3 PD). Amine measurement was non-informative. Multivariate analysis identified NETest >53% as an independent prognostic factor. CONCLUSION: Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated PCC/PGL, scores were elevated in progressive disease irrespective of mutation or biochemical activity and elevated levels were prognostic.

Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations.

BACKGROUND: Thoracic aortic aneurysms and dissections (TAAD) are silent but possibly lethal condition with up to 40 % of cases being hereditary. Genetic background is heterogeneous. Recently next-generation sequencing enabled efficient and cost-effective examination of gene panels. Aim of the study was to define the diagnostic yield of NGS in the 51 TAAD patients and to look for genotype-phenotype correlations within families of the patients with TAAD. METHODS: 51 unrelated TAAD patients were examined by either whole exome sequencing or TruSight One sequencing panel. We analyzed rare variants in 10 established thoracic aortic aneurysms-associated genes. Whenever possible, we looked for co-segregation in the families. Kaplan-Meier survival curve was constructed to compare the event-free survival depending on genotype. Aortic events were defined as acute aortic dissection or first planned aortic surgery. RESULTS AND DISCUSSION: In 21 TAAD patients we found 22 rare variants, 6 (27.3 %) of these were previously reported, and 16 (73.7 %) were novel. Based on segregation data, functional analysis and software estimations we assumed that three of novel variants were causative, nine likely causative. Remaining four were classified as of unknown significance (2) and likely benign (2). In all, 9 (17.6 %) of 51 probands had a positive result when considering variants classified as causative only and 18 (35.3 %) if likely causative were also included. Genotype-positive probands (n = 18) showed shorter mean event free survival (41 years, CI 35-46) than reference group, i.e. those (n = 29) without any plausible variant identified (51 years, CI 45-57, p = 0.0083). This effect was also found when the 'genotype-positive' group was restricted to probands with 'likely causative' variants (p = 0.0092) which further supports pathogenicity of these variants. The mean event free survival was particularly low (37 years, CI 27-47) among the probands with defects in the TGF beta signaling (p = 0.0033 vs. the reference group). CONCLUSIONS: This study broadens the spectrum of genetic background of thoracic aneurysms and dissections and supports its potential role as a prognostic factor in the patients with the disease.

Cardiothoracic ratio may be misleading in the assessment of right- and left-ventricular size in patients with repaired tetralogy of Fallot.

AIM: To assess the relationship between cardiothoracic ratio (CTR) and ventricular and atrial volumes in patients with repaired tetralogy of Fallot (TOF). MATERIALS AND METHODS: Patients with repaired TOF undergoing cardiac magnetic resonance (CMR) and chest radiography within 1 day were included (n = 82; median age: 24.7 years, interquartile range: 21.5-35.9). The CTR was obtained from upright posteroanterior chest roentgenograms. Analyses of CMR images and radiographs were performed in a blinded fashion. RESULTS: There were 35.1% (13/37) of patients with normal CTR (<0.5) who had severe right ventricular (RV) dilatation. There were six patients (13.3%, 6/45) with high CTR with both normal RV and left-ventricular (LV) volumes. CTR did not correlate with either RV or LV volumes but showed a weak correlation with right- and left-atrial volumes (r = 0.43, p = 0.0001; r = 0.27, p = 0.01, respectively). CTR ≥0.5 showed poor ability in the identification of severe RV dilatation (sensitivity: 61.8%, specificity: 50%). The combination of CTR and signs of RV enlargement on lateral radiographs did not improve the diagnostic accuracy of any of those parameters alone. CONCLUSION: CTR in patients with repaired TOF reflected atrial rather than ventricular dilatation. The use of CTR or lateral radiographs in patients with repaired TOF may lead to false conclusions concerning ventricular size.

Clinical characteristics of patients with resistant hypertension: the RESIST-POL study.

Recent studies indicate that resistant hypertension (RHTN) is present in about 12% of the treated hypertensive population. However, patients with true RHTN (confirmed out of the office) have not been widely studied. We prospectively studied 204 patients (123 male, 81 female, mean age 48.4 years, range 19-65 years) with truly RHTN (ambulatory daytime mean blood pressure >135/85 mm Hg). We evaluated the frequency of obstructive sleep apnea (OSA), renal artery stenosis (RAS), primary aldosteronism (PA) and other secondary forms of hypertension (HTN) and conditions. Mild, moderate and severe OSA were present in 55 (27.0%), 38 (18.6%) and 54 (26.5%) patients, respectively. Secondary forms of HTN were diagnosed in 49 patients (24.0%), the most frequent being PA (15.7%) and RAS (5.4%). Metabolic syndrome (MS) was present in 65.7% of patients. Excessive sodium excretion was evident in 33.3% of patients and depression in 36.8% patients. In patients with RHTN, OSA and MS were the most frequent conditions, frequently overlapping with each other and also with PA. Our data indicate that in the vast majority of patients with truly RHTN, at least one of three co-morbidities-OSA, MS and PA-is present. Other conditions, even though less frequent, should also be taken into the consideration.

Renal artery aneurysms: presentation of five cases.

We are presenting clinical characteristics, management and follow-up of five consecutive patients with renal artery aneurysm. Renal artery aneurysms are relatively uncommon, they rarely give rise to clinical manifestations and they are usually found incidentally. However with the introduction of Doppler ultrasound, computed tomography (CT) and magnetic resonance (MR) imaging, the diagnosis of renal artery aneurysms became more frequent.

[Disorders of lipid and lipoprotein metabolism in patients with chronic lymphocytic leukemia. I. Preliminary evaluation of lipemia and HDL fractions in various stages of the disease]. / Zaburzenia metabolizmu lipidów i lipoprotein u chorych z przewlekla bialaczka limfatyczna. Cz. I. Wstepna ocena lipemii i frakcji HDL w róznych okresach choroby.

The study comprised 128 patients with chronic lymphocytic leukemia (CLL) aged 65.7 +/- 8 years, 59 women and 69 men. Among the patients studied 70 were treated and 58 yet not underwent therapy. The Rai classification of patients with CLL has been used. The control group consisted of 68 subjects aged 56.8 +/- 14 years, 35 women and 33 men, showing no diseases affecting the blood lipid disturbances. The following determinations have been performed in the blood serum: apo B, CH, TG, PL, and CH or PL in the isolated HDL fraction; LDL-CH ratio has also been calculated. In patients with CLL the total CH concentration has been noted which advanced parallel to the disease progress. It resulted first of all from the decrease in LDL-CH (p less than 0.05). Similar alterations have been noted so far as apo B is concerned. It has been demonstrated that the decrease in HDL-CH (p less than 0.05) is also dependent on the disease stage. The simultaneously increasing index HDL-PL/HDL-CH indicate on changes within the HDL2 and HDL3 subfractions suggesting a deficiency of the HDL2 subfraction. The total lipemia and the lipoprotein fraction alterations observed make the diagnostic value of the atherosclerotic threat in patients with CLL doubtful with the use of that parameters.