Risks and benefits of renal artery stenting in fibromuscular dysplasia: Lessons from the ARCADIA-POL study.

INTRODUCTION: Although renal stenting is the standard revascularization method for atherosclerotic renal artery stenosis (RAS) (FMD-RAS), stenting in fibromuscular dysplasia (FMD) RAS is usually limited to periprocedural complications of angioplasty and primary arterial dissection. The main aim of the study was to retrospectively analyze the immediate and long-term results of renal stenting versus angioplasty in patients with FMD. METHODS: Of 343 patients in the ARCADIA-POL registry, 58 patients underwent percutaneous treatment due to FMD-RAS (in 70 arteries). Percutaneous transluminal renal angioplasty (PTRA) was performed as an initial treatment in 61 arteries (PTRA-group), whereas primary stenting was undertaken in nine arteries (stent-group). Stent-related complications were defined as: in-stent restenosis > 50% (ISR); stent fracture; under-expansion; or migration. RESULTS: In the PTRA-group, the initial restenosis rate was 50.8%. A second procedure was then performed in 22 arteries: re-PTRA (12 arteries) or stenting (10 arteries). The incidence of recurrent restenosis after re-PTRA was 41.7%. Complications occurred in seven of 10 (70%) arteries secondarily treated by stenting: two with under-expansion and five with ISR. In the stent-group, stent under-expansion occurred in one case (11.1%) and ISR in three of nine stents (33.3%). In combined analysis of stented arteries, either primarily or secondarily, stent-related complications occurred in 11/19 stenting procedures (57.9%): three due to under-expansion and eight due to ISRs. Finally, despite several revascularization attempts, four of 19 (21%) stented arteries were totally occluded and one was significantly stenosed at follow-up imaging. CONCLUSION: Our study indicates that renal stenting in FMD-RAS may carry a high risk of late complications, including stent occlusion. Further observational data from large-scale registries are required.

Ambulatory blood pressure monitoring in treated patients with hypertension in the COVID-19 pandemic - The study of European society of hypertension (ESH ABPM COVID-19 study).

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown profoundly affected almost all aspects of daily life including health services worldwide. The established risk factors for increased blood pressure (BP) and hypertension may also demonstrate significant changes during the pandemic. This study aims to determine the impact of the COVID-19 pandemic on BP control and BP phenotypes as assessed with 24-hour ambulatory BP monitoring (ABPM). MATERIALS AND METHODS: This is a multi-centre, observational, retrospective and comparative study involving Excellence Centres of the European Society of Hypertension across Europe. Along with clinical data and office BP, ABPM recordings will be collected in adult patients with treated arterial hypertension. There will be two groups in the study: Group 1 will consist of participants who have undergone two ABPM recordings - the second one occurring during the COVID-19 pandemic, i.e. after March 2020, and the first one 9-15 months prior to the second. Participants in Group 2 will have two repeated ABPM recordings - both performed before the pandemic within a similar 9-15 month interval between the recordings. Within each group, we will analyse and compare BP variables and phenotypes (including averaged daytime and night-time BP, BP variability, dipper and non-dipper status, white-coat and masked hypertension) between the two respective ABPM recordings and compare these changes between the two groups. The target sample size will amount to least 590 participants in each of the study groups, which means a total of at least 2360 ABPM recordings overall. EXPECTED OUTCOMES: As a result, we expect to identify the impact of a COVID-19 pandemic on blood pressure control and the quality of medical care in order to develop the strategy to control cardiovascular risk factors during unpredictable global events.

What is the context?A wide range of daily activities, including health care worldwide, were deeply affected by the Coronavirus disease 2019 pandemic and the subsequent lockdown.What is new?Our multicenter study will examine the impact of the COVID-19 pandemic on blood pressure control in hypertensive patients across Europe by analysing results of 24-hour ambulatory blood pressure monitoring.What is the impact?Optimising strategies for dealing with future unpredictable global situations will depend on understanding how the pandemic affected blood pressure control.

Fibrin clot properties and fibrinolysis in patients with endocrine hypertension due to aldosterone or catecholamines excess.

OBJECTIVE: The aim of the study was to investigate a new possible background of increased risk of cardiovascular events in two forms of endocrine hypertension: in primary aldosteronism (PA) and pheochromocytoma/paraganglioma (PPGL) in comparison to essential hypertension (EHT). CONTEXT: Prothrombotic properties of the fibrin clot structure, impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk. DESIGN: Patients with PA and PPGL were evaluated at baseline and re-evaluated 3 months after causative treatment. At baseline PA and PPGL patients were compared to matched EHT patients and to healthy controls. PATIENTS: The study included 35 patients with PA, 16 patients with PPGL and two reference groups of patients with EHT (32 and 22 patients) and healthy controls (35 and 23 subjects). MEASUREMENTS: All subjects underwent evaluation according to the study protocol that included plasma fibrin clot permeability (Ks), clot lysis time, endogenous thrombin potential. RESULTS: There were no differences in clot structure and fibrinolytic activity in PA and PPGL patients as compared to matched patients with EHT, whereas all hypertensive groups were characterized by more compact fibrin clot structure, faster clot formation and enhanced thrombin generation in comparison to healthy controls. Both in PA and PPGL patients, fibrin clot properties and fibrinolytic parameters remained stable after the causative treatment. CONCLUSIONS: Patients with PA and PPGL are at a prothrombic state comparable to patients with EHT. The results suggest the higher risk of cardiovascular events observed in hypertensive PA and PPGL as compared to EHT is not mediated through investigated prothrombic mechanisms.

Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy.

BACKGROUND: Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. OBJECTIVE: This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. STUDY DESIGN: Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free ß-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). RESULTS: Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). CONCLUSION: Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

PURPOSE: Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence. MATERIALS AND METHODS: Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres. RESULTS: Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring. CONCLUSIONS: The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.

Intrarenal hemodynamics and kidney function in pheochromocytoma and paraganglioma before and after surgical treatment.

PURPOSE: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function. MATERIALS AND METHODS: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up. RESULTS: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results. CONCLUSIONS: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.

The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism.

OBJECTIVE: To develop a prediction model for clinical outcomes after unilateral adrenalectomy for unilateral primary aldosteronism. SUMMARY BACKGROUND DATA: Unilateral primary aldosteronism is the most common surgically curable form of endocrine hypertension. Surgical resection of the dominant overactive adrenal in unilateral primary aldosteronism results in complete clinical success with resolution of hypertension without antihypertensive medication in less than half of patients with a wide between-center variability. METHODS: A linear discriminant analysis model was built using data of 380 patients treated by adrenalectomy for unilateral primary aldosteronism to classify postsurgical clinical outcomes. The total cohort was then randomly divided into training (280 patients) and test (100 patients) datasets to create and validate a score system to predict clinical outcomes. An online tool (Primary Aldosteronism Surgical Outcome predictor) was developed to facilitate the use of the predictive score. RESULTS: Six presurgical factors associated with complete clinical success (known duration of hypertension, sex, antihypertensive medication dosage, body mass index, target organ damage, and size of largest nodule at imaging) were selected based on classification performance in the linear discriminant analysis model. A 25-point predictive score was built with an optimal cut-off of greater than 16 points (accuracy of prediction = 79.2%; specificity = 84.4%; sensitivity = 71.3%) with an area under the curve of 0.839. CONCLUSIONS: The predictive score and the primary aldosteronism surgical outcome predictor can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to persistent hypertension.

Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma.

Objectives: Plasma free metanephrines are commonly used for diagnosis of pheochromocytoma and paraganglioma (PPGLs), but can also provide other information. This multicenter study prospectively examined whether tumor size, location, and mutations could be predicted by these metabolites. Methods: Predictions of tumor location, size, and mutation type, based on measurements of plasma normetanephrine, metanephrine, and methoxytyramine were made without knowledge of disease in 267 patients subsequently determined to have PPGLs. Results: Predictions of adrenal vs. extra-adrenal locations according to increased plasma concentrations of metanephrine and methoxytyramine were correct in 93 and 97% of the respective 136 and 33 patients in who these predictions were possible. Predicted mean tumor diameters correlated positively (p<0.0001) with measured diameters; predictions agreed well for pheochromocytomas but were overestimated for paragangliomas. Considering only patients with mutations, 51 of the 54 (94%) patients with NF1 or RET mutations were correctly predicted with those mutations according to increased plasma metanephrine, whereas no or minimal increase in metanephrine correctly predicted all 71 patients with either VHL or SDHx mutations; furthermore, among the latter group increases in methoxytyramine correctly predicted SDHx mutations in 93% of the 29 cases for this specific prediction. Conclusions: Extents and patterns of increased plasma O-methylated catecholamine metabolites among patients with PPGLs allow predictions of tumor size, adrenal vs. extra-adrenal locations and general types of mutations. Predictions of tumor location are, however, only possible for patients with clearly increased plasma methoxytyramine or metanephrine. Where possible or clinically relevant the predictions are potentially useful for subsequent clinical decision-making.

Adrenomedullary function, obesity and permissive influences of catecholamines on body mass in patients with chromaffin cell tumours.

BACKGROUND: Obesity-associated activation of sympathetic nervous outflow is well documented, whereas involvement of dysregulated adrenomedullary hormonal function in obesity is less clear. This study assessed relationships of sympathoadrenal function with indices of obesity and influences of circulating catecholamines on body mass. METHODS: Anthropometric and clinical data along with plasma and 24-h urine samples were collected from 590 volunteers and 1368 patients tested for phaeochromocytoma and paraganglioma (PPGL), among whom tumours were diagnosed in 210 individuals. RESULTS: Among patients tested for PPGL, those with tumours less often had a body mass index (BMI) above 30 kg/m2 (12 vs. 31%) and more often a BMI under 25 kg/m2 (56 vs. 32%) than those without tumours (P < 0.0001). Urinary outputs of catecholamines in patients with PPGL were negatively related to BMI (r = -0.175, P = 0.0133). Post-operative weight gain (P < 0.0001) after resection of PPGL was positively related to presurgical tumoural catecholamine output (r = 0.257, P = 0.0101). Higher BMI in men and women and percent body fat in women of the volunteer group were associated with lower plasma concentrations and urinary outputs of adrenaline and metanephrine, the former indicating obesity-related reduced adrenaline secretion and the latter obesity-related reduced adrenomedullary adrenaline stores. Daytime activity was associated with substantial increases in urinary adrenaline and noradrenaline excretion, with blunted responses in obese subjects. CONCLUSIONS: The findings in patients with PPGL support an influence of high circulating catecholamines on body weight. Additional associations of adrenomedullary dysfunction with obesity raise the possibility of a permissive influence of the adrenal medulla on the regulation of body weight.

High incidence and clinical characteristics of fibromuscular dysplasia in patients with spontaneous cervical artery dissection: The ARCADIA-POL study.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

Prevalence of smoking and clinical characteristics in fibromuscular dysplasia. The ARCADIA-POL study.

PURPOSE: Smoking was identified as a potential factor contributing to fibromuscular dysplasia (FMD). To evaluate the prevalence of smoking and clinical characteristics in FMD subjects. MATERIAL AND METHODS: We analysed 190 patients with confirmed FMD in at least one vascular bed. The rate of smokers in FMD patients was compared to that in two control groups selected from a nationwide survey. RESULTS: The rate of smokers in FMD patients was 42.6%. There were no differences in frequency of smokers between FMD patients and: a group of 994 matched control subjects from general population and a group of matched hypertensive subjects. There were no differences in the characteristics of FMD (including rates of multisite FMD and significant renal artery stenosis) and its complications (including rates of dissections and aneurysms) between smokers and non-smokers. Smokers as compared with non-smokers were characterized by higher left ventricle mass index. CONCLUSIONS: There is no difference in the rate of smokers between FMD patients and subjects from the general population. Moreover, we did not find any association between smoking and clinical characteristics of FMD patients nor its extent and vascular complications. Our results do not support the hypothesis that smoking is involved in the pathophysiology of FMD.

Biochemical Diagnosis of Chromaffin Cell Tumors in Patients at High and Low Risk of Disease: Plasma versus Urinary Free or Deconjugated O-Methylated Catecholamine Metabolites.

BACKGROUND: Measurements of plasma or urinary metanephrines are recommended for diagnosis of pheochromocytoma and paraganglioma (PPGL). What test offers optimal diagnostic accuracy for patients at high and low risk of disease, whether urinary free metanephrines offer advantages over deconjugated metanephrines, and what advantages are offered by including methoxytyramine in panels all remain unclear. METHODS: A population of 2056 patients with suspected PPGLs underwent prospective screening for disease using mass spectrometric-based measurements of plasma free, urinary deconjugated, and urinary free metanephrines and methoxytyramine. PPGLs were confirmed in 236 patients and were excluded in others on follow-up evaluation. RESULTS: Measurements of plasma free metabolites offered higher (P < 0.01) diagnostic sensitivity (97.9%) than urinary free (93.4%) and deconjugated (92.9%) metabolites at identical specificities for plasma and urinary free metabolites (94.2%) but at a lower (P < 0.005) specificity for deconjugated metabolites (92.1%). The addition of methoxytyramine offered little value for urinary panels but provided higher (P < 0.005) diagnostic performance for plasma measurements than either urinary panel according to areas under ROC curves (0.991 vs 0.972 and 0.964). Diagnostic performance of urinary and plasma tests was similar for patients at low risk of disease, whereas plasma measurements were superior to both urinary panels for high-risk patients. CONCLUSIONS: Diagnosis of PPGLs using plasma or urinary free metabolites provides advantages of fewer false-positive results compared with commonly measured deconjugated metabolites. The plasma panel offers better diagnostic performance than either urinary panel for patients at high risk of disease and, with appropriate preanalytics, provides the test of choice. Measurements of methoxytyramine in urine show limited diagnostic utility compared with plasma.

Primary Aldosteronism and Obstructive Sleep Apnea: Is This A Bidirectional Relationship?

It has been suggested that the high prevalence of obstructive sleep apnea (OSA) in resistant hypertension (RHT) may be related to the high prevalence of primary aldosteronism (PA) in patients with RHT. It has been also hypothesized that the relationship between aldosterone and OSA might be bidirectional. In patients with RHT, it has been shown that aldosterone levels correlate with severity of OSA and that blockade of aldosterone reduces the severity of OSA. It has been postulated that aldosterone worsens OSA by promoting accumulation of fluid, which shifted in the supine position to the neck, contributes to increased upper airway resistance. Also there is growing data that PA is more frequent in patients with OSA and that the treatment of PA positively influences OSA course. Also in some studies it has been shown that patients with OSA are characterized by higher aldosterone levels and higher prevalence of PA than patients without OSA and that causal treatment of OSA might decrease aldosterone levels. Moreover, the recent guideline of the Endocrine Society on management of PA recommends to screen hypertensive patients with OSA for PA.

GROWTH RATE OF PARAGANGLIOMAS RELATED TO GERMLINE MUTATIONS OF THE SDHX GENES.

OBJECTIVE: The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-related paragangliomas based on computed tomography (CT) measurements. METHODS: Twenty-seven patients with SDHx mutations who underwent subsequent CT examinations were enrolled in the study. Tumors were classified as head and neck (HNP), thoracic, or abdominal/pelvic paragangliomas (PGLs). The percentage volume increase and volume doubling time were estimated. RESULTS: We analyzed 56 PGLs (21 with SDHD, 6 with SDHB mutations) in 27 patients (16 men, 11 women; mean age 37.7 years). The estimated median of the follow-up was 23 months. Twenty-two (39.3%) PGLs were located in the abdomen, 8 (14.3%) in the thorax, and 26 (46.4%) in the head and neck region. The median volume growth rate was estimated at 10.4% per year (interquartile range [IQR]: -1.3; 36.3). The volume doubling time was estimated as 7.01 (2.24;+∞) years. By tumor site, the estimated medians of the annual volume growth rates were 13.6% (IQR:0.8 -30.4) for HNP, -6.06% (IQR: -1.79;47.32) for thoracic PGLs, and 10.5% (IQR: -2.2;44.6) for abdominal PGLs. The volume doubling time was 5.44 years (2.61; 87.0) for HNP, 11.8 years (1.79;+∞) for thoracic PGLs, and 6.94 years (1,88;+∞) for abdominal PGLs. There was no significant difference in the volume growth rate according to tumor location or initial size (P>.7 and P = .07, respectively) or gene mutation type (SDHB vs. SDHD, P>.8). CONCLUSION: PGLs related to SDHx mutations are slowly growing tumors. There were no correlations between tumor location, growth rate or initial size over a 23-month follow-up period. ABBREVIATIONS: CT = computed tomography HNP = head and neck paraganglioma IQR = interquartile range PGL = paraganglioma PPGL = pheochromocytoma and paraganglioma SDH = succinate dehydrogenase.

Evaluation of Head and Neck Paragangliomas by Computed Tomography in Patients with Pheochromocytoma-Paraganglioma Syndromes.

BACKGROUND: Hereditary head and neck paragangliomas (HNP) are very often associated with pheochromocytoma-paraganglioma syndromes, which are caused by mutations in genes encoding subunits of succinate dehydrogenase (SDHx) complex. The aim of this study was to determine the frequency and location of HNP among SDHx carriers. MATERIAL/METHODS: A total of 72 patients with SDHx mutations underwent computed tomography examinations of the head and neck. HNP were present in 44 (61.1%) out of 72 patients (31 SDHD, 11 SDHB, 2 SDHC); 113 HNP were found; the most common were carotid paragangliomas (59) and vagal paragangliomas (27). RESULTS: The HNP were statistically more frequent in carriers of SDHD mutations compared to carriers of SDHB mutations (72.1% vs. 43.5%, p=0.033). Multiple tumors more often occurred in patients with SDHD mutations 26/31 (83.9%) than in patients with SDHB mutations 6/11 (54.5%) p=0.05. There was a significant difference in the prevalence of carotid paragangliomas between patients with SDHB and SDHD mutations (7/11 [63.6%] vs. 30/31 [96.8%], respectively, p=0.004). Patients with SDHD mutations more often had carotid paragangliomas located on the left side than on the right side, as compared to SDHB mutations 25/31 (80.6%) vs. 4/11 (36.4%), p=0.006. CONCLUSIONS: SDHx mutations predispose to multifocal and bilateral HNP. Carotid and vagal paragangliomas occurred most often. Patients with SDHD mutations are characterized by higher frequency of HNP than patients with SDHB mutations, which is mainly driven by higher frequency of carotid body tumors in patients with SDHD mutations. No difference in the frequency of head and neck paragangliomas in other locations was found.

Smaller caliber renal arteries are a novel feature of uromodulin-associated kidney disease.

Hyperuricemia is very common in industrialized countries and known to promote vascular smooth muscle cell proliferation. Juvenile hyperuricemia is a hallmark of uromodulin-associated kidney disease characterized by progressive interstitial renal fibrosis leading to end-stage renal disease within decades. Here we describe a member of a Polish-German family with a history of familial background of chronic kidney disease, hyperuricemia, and gout. This patient had hypertension because of bilateral small renal arteries, hyperuricemia, and chronic kidney disease. Clinical and molecular studies were subsequently performed in 39 family members, which included a physical examination, Duplex ultrasound of the kidneys, laboratory tests for renal function, and urine analysis. In eight family members contrast-enhanced renal artery imaging by computed tomography-angiography or magnetic resonance imaging was conducted and showed that bilateral non-arteriosclerotic small caliber renal arteries were associated with hyperuricemia and chronic kidney disease. Of the 26 family members who underwent genotyping, 11 possessed the P236R mutation (c.707C>G) of the uromodulin gene. All family members with a small caliber renal artery carried the uromodulin P236R mutation. Statistical analysis showed a strong correlation between reduced renal artery lumen and decreased estimated glomerular filtration rate. Thus, bilateral small caliber renal arteries are a new clinical phenotype associated with an uromodulin mutation.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Relationship between hemodynamic parameters of renal artery stenosis and the changes of kidney function after renal artery stenting in patients with hypertension and preserved renal function.

INTRODUCTION: The role of physiological assessment of renal artery stenosis (RAS) using renal fractional flow reserve (rFFR) and resting translesional pressures ratio (Pd/Pa ratio) in the prediction of benefit from revascularization is still unknown. OBJECTIVES: The aim of the study was to assess the relationship between hemodynamic data and the change in kidney function after renal artery stenting in secondary hypertension. PATIENTS AND METHODS: 34 hypertensive patients (50% males, median age 65 years) with at least 60% RAS, underwent stenting and were followed up for 6 months. Pd/Pa ratio (ratio of mean distal to lesion to proximal pressure) and hyperemic rFFR (after papaverine) were measured before the procedure. At baseline and after 6 months, the glomerular filtration rate (eGFR), serum cystatin C and albuminuria were determined. In receiver operating characteristic curves, two previously established cut-off values with the highest accuracy of identifying severe RAS were used: 0.93 for the Pd/Pa ratio and 0.8 for the rFFR. RESULTS: No significant difference in eGFR was found between patients with decreased and normal Pd/Pa ratio (1.4 vs 7.9 ml/min, p = ns). Similarly, minor changes in eGFR were observed in patients with decreased vs normal rFFR (2.4 vs 4.1 ml/min, p = ns). In patients with decreased Pd/Pa ratio, albuminuria remained stable (change 1.4 mg/24 h) compared with an increase of 12.6 mg/24 h in the subgroup with Pd/Pa ≥ 0.93(p < 0.05). However, after exclusion of two outliers with significant baseline proteinuria (425 and 1095 mg/24 h, respectively), the difference in albuminuria change according to the baseline Pd/Pa ratio was no longer maintained. CONCLUSIONS: Hemodynamic parameters of RAS do not distinguish the patients who may benefit from renal artery stenting in terms of kidney function improvement in short-term follow-up.

Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine, metanephrine and methoxytyramine: importance of supine sampling under fasting conditions.

OBJECTIVE: To document the influences of blood sampling under supine fasting versus seated nonfasting conditions on diagnosis of phaeochromocytomas and paragangliomas (PPGL) using plasma concentrations of normetanephrine, metanephrine and methoxytyramine. DESIGN AND METHODS: Biochemical testing for PPGL was performed on 762 patients at six centres, two of which complied with requirements for supine sampling after an overnight fast and four of which did not. Phaeochromocytomas and paragangliomas were found in 129 patients (67 noncompliant, 62 compliant) and not in 633 patients (195 noncompliant, 438 compliant). RESULTS: Plasma concentrations of normetanephrine and methoxytyramine did not differ between compliant and noncompliant sampling conditions in patients with PPGL but were 49-51% higher in patients without PPGL sampled under noncompliant compared with compliant conditions. The 97·5 percentiles of distributions were also higher under noncompliant compared with compliant conditions for normetanephrine (1·29 vs 0·79 nmol/l), metanephrine (0·49 vs 0·41 nmol/l) and methoxytyramine (0·42 vs 0·18 nmol/l). Use of upper cut-offs established from seated nonfasting sampling conditions resulted in substantially decreased diagnostic sensitivity (98% vs 85%). In contrast, use of upper cut-offs established from supine fasting conditions resulted in decreased diagnostic specificity for testing under noncompliant compared with compliant conditions (71% vs 95%). CONCLUSIONS: High diagnostic sensitivity of plasma normetanephrine, metanephrine and methoxytyramine for the detection of PPGL can only be guaranteed using upper cut-offs of reference intervals established with blood sampling under supine fasting conditions. With such cut-offs, sampling under seated nonfasting conditions can lead to a 5·7-fold increase in false-positive results necessitating repeat sampling under supine fasting conditions.

Pheochromocytoma presenting as takotsubo-like cardiomyopathy following delivery.

OBJECTIVE: Diagnosis of pheochromocytoma during pregnancy can be difficult, and the tumor carries an unfavorable prognosis if not diagnosed and treated in a timely manner. METHODS: To present a case of Takotsubo-like cardiomyopathy characterized by transient left ventricular apical ballooning due to pheochromocytoma following delivery. RESULTS: A few hours after Caesarean section, a 32-year-old Caucasian female presented with pulmonary edema followed by cardiac arrest with echocardiographic and ventriculographic evidence of reversible acute myocardial failure characteristic of Takotsubo-like cardiomyopathy. A previously unrecognized adrenal pheochromocytoma was found during her clinical work-up. Left ventricle (LV) function normalized after surgical removal of the tumor, which was carried out after implementing an alpha-adrenoreceptor blockade. Hemorrhagic necrosis of the pheochromocytoma was seen on histopathologic analysis; this may have triggered the sequence of events leading to the development of Takotsubo-like cardiomyopathy and hemodynamic collapse. CONCLUSION: To the best of our knowledge, this is the first reported case of Takotsubo-like cardiomyopathy related to pheochromocytoma following delivery. This emphasizes the increased cardiovascular risk if pheochromocytoma is not diagnosed and treated in a timely manner, especially during pregnancy.