Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events.

'Essential' arterial hypertension: time for a paradigm change.

The exclusion of causes of hypertension is not systematically exploited in clinical practice. Therefore, essential hypertension is consistently presented as the most prevalent 'cause'. The paradox of a condition with unknown causes being described as a common cause of hypertension translates into a diagnosis of essential hypertension in most patients, which precludes the detection of a curable cause of hypertension.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment.

Methods: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers.

Tangram of Sodium and Fluid Balance.

Homeostasis of fluid and electrolytes is a tightly controlled physiological process. Failure of this process is a hallmark of hypertension, chronic kidney disease, heart failure, and other acute and chronic diseases. While the kidney remains the major player in the control of whole-body fluid and electrolyte homeostasis, recent discoveries point toward more peripheral mechanisms leading to sodium storage in tissues, such as skin and muscle, and a link between this sodium and a range of diseases, including the conditions above.

Coronary sinus diameter to estimate congestion and predict survival.

Background: Congestion predicts a poor prognosis, but its assessment is challenging in clinical practice and requires a multiparametric approach. We investigated if the coronary sinus (CS) diameter can predict mortality in a human model of rapid fluid unloading.

Methods: We measured by echocardiography the CS, and the inferior vena cava (IVC) for comparison, in 60 patients with end-stage chronic kidney disease (ESKD) immediately before and after hemodialysis (HD; age 76 [57-81] years, 40% female, left ventricular ejection fraction 57 [53-56]%).

Lymphatic vessels and the renin-angiotensin-system.

The lymphatic system is an integral part of the circulatory system and plays an important role in the fluid homeostasis of the human body. Accumulating evidence has recently suggested the involvement of lymphatic dysfunction in the pathogenesis of cardio-reno-vascular (CRV) disease. However, how the sophisticated contractile machinery of lymphatic vessels is modulated and, possibly impaired in CRV disease, remains largely unknown.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

Background: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation.

Objectives: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal.

Methods: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference.

Primary Aldosteronism and Drug Resistant Hypertension: A "Chicken-Egg" Story.

Drug-resistant arterial hypertension (RH) is a major risk factor for cardiovascular disease, often due to overlooked underlying causes. Identification of such causes poses significant clinical challenges. In this setting, primary aldosteronism (PA) is a frequent cause of RH and its prevalence in RH patients is likely higher than 20%.

Skin-specific mechanisms of body fluid regulation in hypertension.

Increasing evidence suggests excess skin Na+ accumulation in hypertension; however, the role of skin-specific mechanisms of local Na+/water regulation remains unclear. We investigated the association between measures of sweat and trans-epidermal water loss (TEWL) with Na+ content in the skin ([Na+]skin) and clinical characteristics in consecutive hypertensive patients. We obtained an iontophoretic pilocarpine-induced sweat sample, a skin punch biopsy for chemical analysis, and measures of TEWL from the upper limbs.

Exclusion Tests in Unilateral Primary Aldosteronism (ExcluPA) Study.

Context: Determining the diagnostic accuracy of "exclusion" tests for primary aldosteronism (PA) compared to the aldosterone to renin ratio (ARR) is fundamental to avoid invasive subtyping in false-positive patients at screening.

Objective: To assess the accuracy of exclusion tests for PA using the diagnosis of unilateral PA as reference.

Methods: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published from January 1, 1970, to December 31, 2021, meeting tight quality criteria.

Does Excess Tissue Sodium Storage Regulate Blood Pressure?

Purpose Of Review: The regulation of blood pressure is conventionally conceptualised into the product of "circulating blood volume" and "vasoconstriction components". Over the last few years, however, demonstration of tissue sodium storage challenged this dichotomous view.

Recent Findings: We review the available evidence pertaining to this phenomenon and the early association made with blood pressure; we discuss open questions regarding its originally proposed hypertonic nature, recently challenged by the suggestion of a systemic, isotonic, water paralleled accumulation that mirrors absolute or relative extracellular volume expansion; we present the established and speculate on the putative implications of this extravascular sodium excess, in either volume-associated or -independent form, on blood pressure regulation; finally, we highlight the prevalence of high tissue sodium in cardiovascular, metabolic and inflammatory conditions other than hypertension.

Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy.

Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats.

Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension.

Modern Management of Hypertensive Emergencies.

Acute increases of blood pressure values are common causes of patients' presentation to emergency departments, and their management represents a clinical challenge. They are usually described as 'hypertensive crises', 'hypertensive urgencies', terms that should be abandoned because they are misleading and inappropriate according to a recent task force of the European Society of Cardiology, which recommended to focus only on 'hypertensive emergencies'. The latter can be esasily identified by using the Brain, Arteries, Retina, Kidney, and/or Heart (BARKH) strategy as herein described.

Mechanisms of sodium-mediated injury in cardiovascular disease: old play, new scripts.

There is a strong association between salt intake and cardiovascular diseases, particularly hypertension, on the population level. The mechanisms that explain this association remain incompletely understood and appear to extend beyond blood pressure. In this review, we describe some of the 'novel' roles of Na in cardiovascular health and disease: energetic implications of sodium handling in the kidneys; local accumulation in tissue; fluid dynamics; and the role of the microvasculature, with particular focus on the lymphatic system.

Identification of Surgically Curable Primary Aldosteronism by Imaging in a Large, Multiethnic International Study.

Context: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy.

Objective: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging.

Management of hypertensive emergencies: a practical approach.

Acute increases of high blood pressure values, usually described as 'hypertensive crises', 'hypertensive urgencies' or 'hypertensive emergencies', are common causes of patients' presentation to emergency departments. Owing to the lack of ad hoc randomized clinical trials, current recommendations/suggestions for treatment of these patients are not evidenced-based and, therefore, the management of acute increases of blood pressure values represent a clinical challenge. However, an improved understanding of the underlying pathophysiology has changed radically the approach to management of the patients presenting with these conditions in recent years.

Drug-resistant hypertension in primary aldosteronism patients undergoing adrenal vein sampling: the AVIS-2-RH study.

Aims: We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres.

Methods And Results: The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years.