Clinical Outcomes of 1625 Patients With Primary Aldosteronism Subtyped With Adrenal Vein Sampling.

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220.

A prediction model for primary aldosteronism when the salt loading test is inconclusive.

OBJECTIVE: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT). CONTEXT: Diagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data. DESIGN: We included a retrospective cohort of 276 patients in the final analysis. METHODS: All patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140-280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques. RESULTS: The following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively. CONCLUSIONS: We developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel.

A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence.

BACKGROUND: With the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN). This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis. METHODS: Data Sources: Studies from recent meta-analyses for RDN and placebo effect were supplemented with a systematic search for MRAs in ATRHTN in the Pubmed, EMBASE, CINAHL and Cochrane databases through November 2016. STUDY SELECTION: Randomized controlled trials comparing treatment options for patients with ATRHTN. DATA EXTRACTION AND SYNTHESIS: Data were extracted using predefined data extraction forms, including the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. A Bayesian random effects model was used to conduct a network meta-analysis. Spironolactone was used as the main comparator. Main Outcomes and Measures: Reduction in 24-h ambulatory blood pressure measurement (ABPM). RESULTS: Twenty articles met our inclusion criteria, and seven treatment alternatives were compared. Compared to MRA, CAA had the highest probability of being more effective, further reducing 24-h SBP (-4.8 mmHg [-13.0, 3.7]) and 24-h DBP (-9.7 mmHg [-18, -0.63]). This difference is likely to be clinically meaningful, with a probability of 78 and 96% at a threshold of a 2-mmHg reduction in blood pressure. CONCLUSIONS: When compared to MRA as anchor, darusentan, CAA and RDN are not more effective in achieving a clinically significant reduction in ambulatory blood pressure in individuals with apparent treatment-resistant hypertension.

Neurocognitive function in dopamine-ß-hydroxylase deficiency.

Dopamine-ß-hydroxylase (DßH) deficiency is a rare genetic syndrome characterized by the complete absence of norepinephrine in the peripheral and the central nervous system. DßH-deficient patients suffer from several physical symptoms, which can be treated successfully with L-threo-3,4-dihydroxyphenylserine, a synthetic precursor of norepinephrine. Informal clinical observations suggest that DßH-deficient patients do not have obvious cognitive impairments, even when they are not medicated, which is remarkable given the important role of norepinephrine in normal neurocognitive function. This study provided the first systematic investigation of neurocognitive function in human DßH deficiency. We tested 5 DßH-deficient patients and 10 matched healthy control participants on a comprehensive cognitive task battery, and examined their pupil dynamics, brain structure, and the P3 component of the electroencephalogram. All participants were tested twice; the patients were tested once ON and once OFF medication. Magnetic resonance imaging scans of the brain revealed that the patients had a smaller total brain volume than the control group, which is in line with the recent hypothesis that norepinephrine has a neurotrophic effect. In addition, the patients showed an abnormally small or absent task-evoked pupil dilation. However, we found no substantial differences in cognitive performance or P3 amplitude between the patients and the control participants, with the exception of a temporal-attention deficit in the patients OFF medication. The largely spared neurocognitive function in DßH-deficient patients suggests that other neuromodulators have taken over the function of norepinephrine in the brains of these patients.

Optimal dose of losartan for renoprotection in diabetic nephropathy.

BACKGROUND: Angiotensin II subtype-1 receptor antagonists represent a valuable new class of drugs in the treatment of diabetic nephropathy. The aim of our study was to evaluate the optimal dose of losartan for renoprotection and blood pressure reduction in diabetic nephropathy. METHODS: Fifty consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan reduced albuminuria and blood pressure. Albuminuria was reduced by 30% (95% CI (15-41)) on losartan 50 mg, 48% (35-57) by losartan 100 mg, and 44% (32-56) by losartan 150 mg (all P values <0.01 vs baseline). Losartan 100 mg daily was significantly more effective than 50 mg daily in reducing albuminuria (P<0.01) without differences between the two high doses. Losartan 50, 100, and 150 mg daily decreased systolic/diastolic blood pressures by 7/4, 12/6, and 10/5 mmHg, respectively (all P<0.05). Losartan 100 mg daily was more effective than 50 mg daily in reducing systolic, diastolic, and mean arterial blood pressure (P=0.05), without differences between the high doses. Treatment with losartan 100 and 150 mg lowered GFR by 4 ml/min/1.73 m(2) (P<0.05). CONCLUSION: Our study suggests that the optimal dose of losartan is 100 mg daily for renoprotection and blood pressure reduction in type 1 diabetic patients with diabetic nephropathy.