Search Results (161)

The pivotal role of angiotensin II (AngII) in cardiovascular disease has been firmly established, as evidenced by a robust body of literature and the broad clinical application of AngII-inhibiting therapies. AngII type 1 receptor is the primary mediator of AngII action, and its activation initiates a multitude of cellular responses that contribute to the development of hypertension, structural changes in the heart and vasculature, and damage to target organs. This review examines AngII from a different perspective, exploring the link between the renin–angiotensin–aldosterone system and cardiovascular risk beyond hypertension, with particular emphasis on atherosclerosis development and progression. Full article

Background/Objectives: While aldosterone excess has a detrimental impact on the left ventricle, no data exist concerning right ventricular (RV) function in primary aldosteronism (PA) patients. We aimed to assess RV structure and function in patients with PA using cardiac magnetic resonance imaging. Methods: Thirty PA patients and 30 age- and sex-matched healthy volunteers were studied. All patients underwent cardiac magnetic resonance with the assessment of RV structure and function. Results: Neither the RV mass index (RVMi) nor the RV ejection fraction (RVEF) correlated with the aldosterone levels (p = 0.36 and p = 0.37, respectively). On the contrary, we found a weak positive correlation between the RV end-diastolic volume index (RVEDVi) and aldosterone concentration (rho = 0.5, p = 0.005). Neither the RVEDVi nor the RVEF differed between the PA patients and the control group (p = 0.077 and p = 0.93, respectively). The RVMi was higher in the PA group, at 18.9 (4.9) g/m², versus 13.6 (3.2) g/m² (SD) in the control group (p < 0.0001). The RVEDVi was positively correlated with the duration of hypertension (rho = 0.4, p = 0.03), and the latter was correlated inversely with the RVEF (rho = −0.47, p = 0.009). The RV global longitudinal strain was impaired in PA patients in comparison with the controls (−16.8 (2.5%) versus −19.6 (2.7%), p = 0.0001). Conclusions: The PA patients exhibited larger RVMi values than the controls. The higher the aldosterone levels were, the higher the observed RVEDVi. Additionally, the longer the duration of hypertension, the higher the observed RVEDVi and the lower the noted RVEF. The PA patients exhibited subclinical RV systolic dysfunction, expressed as impaired RV global longitudinal strain. Full article

Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via mineralocorticoid receptor activation, oxidative stress, inflammation, and extracellular matrix dysregulation. These changes culminate in a distinct cardiomyopathy phenotype, often underrecognized in early stages. Multimodality cardiac imaging, led primarily by conventional and speckle-tracking echocardiography, and complemented by exploratory cardiac magnetic resonance (CMR) techniques such as T1 mapping and late gadolinium enhancement, enables non-invasive assessment of structural, functional, and tissue-level changes in aldosterone-mediated myocardial damage. While numerous studies have established the diagnostic and prognostic relevance of imaging in PA, several gaps remain. Specifically, the relative sensitivity of different modalities in detecting subclinical myocardial changes, the long-term prognostic significance of imaging biomarkers, and the differential impact of adrenalectomy versus medical therapy on cardiac reverse remodeling require further clarification. Moreover, the lack of standardized imaging-based criteria for defining and monitoring PA-related cardiomyopathy hinders widespread clinical implementation. This narrative review aims to synthesize current knowledge on the pathophysiological mechanisms of aldosterone-induced cardiac remodeling, delineate the strengths and limitations of existing imaging modalities, and critically evaluate the comparative effects of surgical and pharmacologic interventions. Emphasis is placed on early detection strategies, identification of imaging biomarkers with prognostic utility, and integration of multimodal imaging into clinical decision-making pathways. By outlining current evidence and highlighting key unmet needs, this review provides a framework for future research aimed at advancing personalized care and improving cardiovascular outcomes in patients with PA. Full article

Background/Objectives: Perioperative hypotension during kidney transplantation poses a risk to graft function and survival. Angiotensin II (AngII) is an endogenous vasoconstrictor targeting the renin–angiotensin–aldosterone system (RAAS) to increase blood pressure. Black patients may have a different response to synthetic angiotensin II (AT2S) compared to non-Black patients, given differential expressions in renin profiles. The purpose of this study is to assess the difference between Black and non-Black patients in total vasopressor duration and usage when AT2S is first line for hypotension during kidney transplantation. Methods: A single-center, retrospective cohort study comparing Black and non-Black patients who required AT2S as a first-line vasopressor for hypotension during the perioperative period of kidney transplantation. Results: The primary outcome evaluating total usage of vasopressors found that Black patients required longer durations of vasopressors (36.9 ± 66.8 h vs. 23.7 ± 31.7 h; p = 0.022) but no difference in vasopressor amount (0.07 ± 0.1 NEE vs. 0.05 ± 0.1 NEE; p = 0.128) compared to non-Black patients. Regression analysis found that body weight was associated with the duration of vasopressors (p < 0.05), while baseline systolic blood pressure was inversely associated with it. Longer duration of vasopressors and duration of transplant surgery were associated with delayed graft function in regression analysis (p < 0.05). Conclusions: Black patients had a longer duration of vasopressors, but this was not driven by differences in usage of AT2S. As baseline weight was significantly higher in Black patients and associated with duration of usage, perhaps the metabolic differences in our Black patients led to the observed differences. Regardless, longer durations of vasopressors were associated with delayed graft function, making this an area of utmost importance for continued investigation. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances. Hormonal evaluations confirmed primary adrenocortical insufficiency, necessitating ongoing hydrocortisone and fludrocortisone therapy. Using family trio-based amplicon sequencing of the CYP21A2 gene, we identified compound heterozygosity consisting of a full gene deletion and a novel pathogenic intronic mutation. Additionally, analysis of WGS data was performed to rule out pathogenic variants in genes that might lead to a similar phenotype, thereby eliminating the possibility of other genes contributing to the proband’s disease. This case demonstrates the potential of using amplicon sequencing in molecular genetic diagnostic testing to detect rare intronic variants in the CYP21A2 gene in cases of early-onset adrenal failure. It also contributes to a better understanding of the genetic basis of congenital adrenal hyperplasia (CAH), which remains a significant autosomal recessive disorder affecting cortisol and aldosterone production, with an incidence of 1 in 10,000 to 1 in 15,000 globally. Full article

Background/Objectives: Adrenal vein sampling is the gold standard for differentiating between unilateral and bilateral primary aldosteronism and guiding treatment. This study evaluates the utility of inspiratory CT scans in interventional planning, specifically assessing the right adrenal vein visualization and positional discrepancies during fluoroscopy. Methods: A retrospective analysis of 133 patients who underwent adrenal vein sampling was performed. Pre-procedural inspiratory CT scans were reviewed for visualization and location of the right adrenal vein using vertebral body levels as reference. The position of the right adrenal vein was then compared with the fluoroscopic findings during adrenal veins sampling. Results: The right adrenal vein was visualized on CT scans in 99.2% of patients. Cohen’s kappa demonstrated almost perfect agreement for both visualization of the right adrenal vein and position measurement. A median difference of three vertebral levels was observed between the level of the right adrenal vein on CT and fluoroscopy, with fluoroscopy showing a more cranial position in 91.7% of cases. Conclusions: Inspiratory CT scans visualize the right adrenal vein effectively and aid the planning of adrenal vein sampling. Understanding the positional discrepancies caused by respiratory motion is crucial for successful cannulation of the right adrenal vein, minimizing procedure time and contrast consumption and ultimately enhancing patient outcomes in the management of primary aldosteronism. Full article

Contrast-associated acute kidney injury (CA-AKI) is a known complication of endovascular procedures using an iodinated contrast medium (ICM), especially in patients with peripheral artery disease (PAD) and chronic kidney disease (CKD). This retrospective study evaluated the incidence and risk factors of AKI in patients with PAD and CKD undergoing diagnostic angiography or endovascular intervention using carbon dioxide (CO₂) as the primary contrast medium, with optional bailout ICM use. We included 340 patients who underwent peripheral angiography or intervention between September 2014 and December 2020. CO₂ was used as the primary contrast medium for all patients, as the majority were classified with advanced CKD stages 3–5 according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Bailout ICM was used in 80% of cases (mean 21.23 ± 14.09 mL). Postinterventional AKI occurred in 13.2% of patients, with over 70% classified as stage 1. Seven patients required new dialysis within 7 days. Multivariate analysis identified hypertension, heart failure, and coronary artery disease as independent AKI risk factors. Statin or Renin–Angiotensin–Aldosteron System (RAAS) inhibitor use and higher pre-interventional GFR were protective. AKI remains common in patients undergoing CO₂-guided peripheral procedures. Further studies are needed to explore underlying mechanisms and outcomes. Full article

Hypertension is a critical health concern as it affects millions of people worldwide and leads to increased risk factors for other diseases such as cardiovascular diseases and stroke. Hypertension is commonly categorized into primary hypertension and secondary hypertension, with the latter frequently curable when caused by the presence of a benign adrenal adenoma that produces excessive adrenal hormones. The incidence rate of these adrenal adenomas is relatively high, in keeping with the hyperplastic/hypermutable characteristic of the adrenal gland. One of the most common functional adrenal adenomas are the aldosterone-producing adenomas (APAs), which develop from the adrenal cortex and, as per the name, produce excessive amounts of the adrenal hormone aldosterone, leading to hypertension. Investigations of genetic causes of these adenomas have revealed that the de novo somatic mutations that commonly cause the increase in aldosterone production mostly involve changes in intracellular concentration. Herein, we review the somatic genetic alterations that have been reported in APAs over the decade. Full article

Background: Primary aldosteronism is characterized by elevated aldosterone levels, leading to adverse effects such as hypertension, hypokalaemia and increased risk for cardiovascular and cerebrovascular events. Aldosterone impacts the central nervous system by promoting vascular remodelling and oxidative stress, potentially impairing cognitive function. The presence of mineralocorticoid receptors in the hippocampus, a key region for cognition, further suggest a link between primary aldosteronism and cognitive dysfunction. This study aims to further explore the association between hyperaldosteronism and cognitive impairment. Methods: In this pilot study we examined 15 individuals with primary aldosteronism and arterial hypertension alongside 15 age- and sex-matched controls with essential hypertension, all free of previous cerebrovascular events. Clinical and archival laboratory data were obtained. Cognitive function was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results: Participants with primary aldosteronism had higher blood pressure values, longer duration of hypertension, lower serum potassium levels and higher 24 h urine albumin excretion rate compared to controls. Comorbidities, other characteristics and laboratory values were comparable across the two groups. No differences were observed in Mini-Mental State Examination scores, but Montreal Cognitive Assessment scores were significantly lower in the primary aldosteronism group (25.1 ± 2.2 vs. 27.1 ± 2.2, p = 0.021). Trends of poorer performance in language and attention/executive function domains were noted in primary aldosteronism individuals, as well as a higher number of pathological Montreal Cognitive Assessment scores (7 vs. 3). No significant correlations were found between cognitive test results and aldosterone concentrations or blood pressure in primary aldosteronism group. However, importantly, multiple regression analysis showed that aldosterone levels have a significant impact on Montreal Cognitive Assessment test, independent of blood pressure or duration of hypertension. Conclusions: This study supports an association between hyperaldosteronism and cognitive dysfunction, underscoring the need for more active detection and targeted treatment of primary aldosteronism. These findings warrant further research in larger cohorts to better elucidate this relationship. Full article

Background/Objectives: Pseudohypoaldosteronism type 1 (PHA-1) is a rare disorder characterized by aldosterone resistance, leading to hyponatremia, hyperkalemia, and elevated renin and aldosterone levels in neonates and infants. While genetic mutations in NR3C2 (mineralocorticoid receptor, MR) and SCNN1A/B/G (epithelial sodium channel, ENaC) are established causes of primary PHA-1, cases without detectable mutations have also been reported. This study aimed to compare the clinical characteristics of genetically confirmed PHA-1 cases—with or without mutations—and to assess genotype–phenotype correlations. Methods: A literature review was conducted using the Medline database, covering studies published from 1966 to October 2023. Included cases were diagnosed with PHA-1 and had undergone genetic testing for NR3C2 and SCNN1A/B/G. Clinical and biochemical data were compared across three groups: MR, ENaC, and non-mutation. Additional subgroup analysis based on mutation type (truncating vs. non-truncating) was also performed. Results: A total of 164 patients from 64 studies met the inclusion criteria. The ENaC group showed significantly higher serum potassium levels than the MR and non-mutation groups. Serum aldosterone levels were significantly higher in the MR group compared to the non-mutation group. A genotype–phenotype correlation was evident in the ENaC group, with truncating variants associated with more severe hyperkalemia. No such correlation was observed in the MR group. Conclusions: This review highlights distinct clinical features of PHA-1 according to genetic status. Aldosterone levels may aid in guiding decisions regarding genetic testing. Furthermore, variant type in ENaC-related PHA-1 may predict biochemical severity and should be considered in clinical management strategies. Full article

Aldosterone, a mineralocorticoid hormone synthesised in the adrenal cortex, is essential for maintaining electrolyte balance and fluid homeostasis. Its role in feline physiology remains underexplored, despite its importance in regulating sodium reabsorption and potassium excretion via mineralocorticoid receptors in renal tubules. This study is warranted given aldosterone’s importance in cats, particularly in light of their unique physiological traits, including highly concentrated urine and sensitivity to hydration status. Primary hyperaldosteronism, the most common feline adrenocortical disorder, contributes to arterial hypertension and chronic kidney disease, yet often remains underdiagnosed due to overlapping symptoms like hypokalaemia and hypertension. This research aimed to validate a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to measure serum aldosterone and to establish a reference interval in a population of healthy cats across a broad age range. The method demonstrated high precision and accuracy, with inter-assay coefficients of variation under 15%. Analysis of 49 healthy cats (40 young, 9 old) revealed a reference interval of 5.0–78.4 pg/mL (13.8–217.2 pmol/L). These findings provide a robust framework for diagnosing aldosterone-related disorders in cats and underscore the need for species-specific diagnostic tools. Improved understanding of aldosterone’s role could refine treatment strategies and enhance outcomes for affected feline patients. Full article

Heart failure (HF) remains a global health burden with high morbidity and mortality, despite significant pharmacological advances. Vitamin D deficiency (VDD) is commonly observed in HF patients and may exacerbate disease progression through various pathophysiological mechanisms, including activation of the renin–angiotensin–aldosterone system, inflammation, oxidative stress, and impaired calcium homeostasis. While vitamin D (VD) supplementation may positively influence surrogate markers in selected patient groups—particularly those with reduced ejection fraction or severe vitamin D deficiency—its effect on primary endpoints such as mortality or HF-related hospitalization varies significantly across studies and patient populations. As a result, while VD supplementation may benefit VD-deficient HF patients, current evidence does not support routine administration across the whole HF population. It is still a matter of debate whether VDD belongs to prognostic markers of worse outcomes in HF or is instead their potential cause. Therefore, the clinical utility of VD in HF management remains underexplored. This review aims to assess the evidence regarding vitamin D status and its supplementation in the context of HF, with a focus on different HF phenotypes: reduced (HFrEF), mildly reduced (HFmrEF), and preserved ejection fraction (HFpEF). The aim is to synthesize findings from novel observational studies, randomized controlled trials, and meta-analyses that shed light onto this intricate relationship and may be valuable in everyday clinical practice. Full article

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and is a risk factor for progression to end-stage kidney disease and cardiovascular morbidity and mortality. Despite pharmacologic treatment, residual risk of disease progression and adverse outcomes remains substantial. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) approved in the United States for use in patients with CKD associated with T2D. The present review focuses on finerenone use, including its pharmacologic basis, indication and eligibility, and practical aspects of incorporation into routine clinical practice (particularly primary care). Results from the two placebo-controlled phase 3 clinical trials of finerenone (plus maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor) in patients with CKD associated with T2D showed a significantly lower risk of CKD progression and cardiovascular events with finerenone versus placebo. These effects of finerenone were applicable across the broad spectrum of patient participants, including those with baseline comorbidities such as a history of heart failure or a history of atherosclerotic cardiovascular disease. We also compare finerenone to steroidal MRAs and discuss the relevance of ongoing and recently completed clinical trials of finerenone in other patient groups, which could expand finerenone use further to a broader spectrum of patients. Full article

Esaxerenone, which blocks aldosterone binding, is approved to treat hypertension but not heart failure. We aimed to understand esaxerenone’s efficacy in treating chronic heart failure. This crossover study compared esaxerenone with eplerenone, an approved treatment for heart failure, in 66 patients with chronic heart failure complicated by hypertension (12 months for each drug). The primary endpoint was brain natriuretic peptide. The secondary endpoints included blood pressure; hormones and enzymes that regulate electrolytes and stress response; and biomarkers of kidney function. Change in brain natriuretic peptide concentration was significantly lower for esaxerenone compared with eplerenone at 3, 6, and 12 months. Blood pressure (all time points), plasma aldosterone concentration (3 and 6 months), and urinary albumin-to-creatinine ratio (3 and 6 months) were significantly lower for esaxerenone compared with eplerenone. The results suggest that esaxerenone more strongly blocks aldosterone binding than does eplerenone. This effect, together with its strong antihypertensive effect and reduced urinary albumin-to-creatinine ratio, suggests that esaxerenone improves kidney function. The results of this small-scale, single-center study need to be expanded to a larger-scale investigation, but esaxerenone shows promise as a treatment for chronic heart failure with hypertension. Full article