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Abstract Background Primary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit. Methods This prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022. Results At follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group. Conclusion For PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Abstract Objectives Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv‐PN) and cardiomyopathy (ATTRv‐CM). The long‐term efficacy of diflunisal on both polyneuropathy and cardiomyopathy in ATTRv patients, especially those with non‐V30M genotypes, has not been fully investigated and compared with that of tafamidis. Methods We compared the structural and biochemical characteristics of A97S‐TTR complexed with tafamidis with those of diflunisal, and prospectively followed up and compared the progression of polyneuropathy and cardiomyopathy between ATTRv‐PN patients taking diflunisal and those taking tafamidis. Results Both diflunisal and tafamidis effectively bind to the two thyroxine‐binding sites at the A97S‐TTR dimer–dimer interface and equally and almost sufficiently reduce amyloid fibril formation. Thirty‐five ATTRv‐PN patients receiving diflunisal and 22 patients receiving tafamidis were enrolled. Compared with no treatment, diflunisal treatment significantly delayed the transition of FAP Stage 1 to 2 and Stage 2 to 3 and decreased the deterioration in parameters of the ulnar nerve conduction study (NCS). The progression of FAP stage or NCS parameters did not differ between patients treated with diflunisal and those treated with tafamidis. Both diflunisal and tafamidis treatments significantly decreased radiotracer uptake on 99mTc‐PYP SPECT and stabilized cardiac wall thickness and blood pro‐B‐type natriuretic peptide levels. No significant adverse events occurred during diflunisal or tafamidis treatment. Interpretations The binding patterns of both tafamidis and diflunisal to A97S‐TTR closely resembled those observed in the wild type. Diflunisal can effectively delay the progression of polyneuropathy and cardiomyopathy with similar efficacy to tafamidis and may become a cost‐effective alternative treatment for late‐onset ATTRv‐PN.

Background: The aldosterone-to-renin ratio (ARR) is commonly used for screening primary aldosteronism (PA) in patients with difficult-to-control hypertension. Various thresholds have been proposed for the confirmatory tests, leading to inconsistency in the results. Objectives: This study aimed to elucidate the performance of ARR screening in hypertensive patients. Design: Systemic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2024. Studies that used the ARR to screen for PA and provided a comprehensive probability panel specifically focusing on hypertensive individuals were considered for enrollment. Pooled diagnostic efficacy was evaluated, and subgroup analyses and meta-regression were conducted based on different demographic and clinical parameters. Results: Eighteen observational studies encompassing 7150 participants were included in the meta-analysis. The overall prevalence of PA in the hypertensive cohort was 15.2%, and pooled sensitivity and specificity were 81.6% and 93.3%, respectively, resulting in a diagnostic odds ratio of 62.0. Fagan’s nomogram showed that a positive ARR increased the post-test probability to 80% from a pre-test probability of 25%. Summary receiver operating characteristic curve analysis revealed an area under the curve of 94.7%. Notably, analysis of variability demonstrated that the diagnostic performance was consistent across either ARR based on plasma renin activity or direct renin concentration, geographic region, sex, mean age, potassium level, and systolic blood pressure. Conclusion: ARR was validated as a viable screening methodology for PA in hypertensive individuals. Moreover, its diagnostic efficacy remained unchanged across diverse clinical contexts. Future studies are warranted to refine ARR methodologies and enhance diagnostic accuracy. Trial registration: PROSPERO ID number CRD42023493680. Infographics Performance of PA screening by ARR. ARR, aldosterone-to-renin ratio; BP, blood pressure; DRC, direct renin concentration; hsROC, hierarchical summary receiver operating characteristic; PA, primary aldosteronism; PRA, plasma renin activity.

Background: Patients with primary aldosteronism (PA) exhibit a high prevalence of diabetes mellitus (DM). However, the relationship between visceral adipose tissue (VAT) and new-onset diabetes mellitus (NODM) in PA patients remains unclear. Objectives: To explore the association between VAT and the risk of NODM in PA patients. Design: This is a prospective cohort study spanning 10 years (2010–2020). Methods: A total of 342 PA patients were enrolled prospectively. Abdominal adiposity indexes, including VAT area, VAT ratio, subcutaneous adipose tissue (SAT) area, and SAT ratio, were measured using a computed tomography-based software at diagnosis. Results: Of 342 PA patients (46.2% male, mean age 50.8 ± 11.2 years), 35 (10.2%) developed NODM over a mean follow-up of 7.4 years. A positive nonlinear association between NODM risk and Log (VAT ratio) ⩾ −0.72 was observed (high-VAT group). High VAT (odds ratio (OR), 6.09; p = 0.005), older age (OR, 1.09; p

Abstract Metabolites are essential molecules involved in various metabolic processes, and their deficiencies and excessive concentrations can trigger significant physiological consequences. The detection of multiple metabolites within a non‐invasively collected biofluid could facilitate early prognosis and diagnosis of severe diseases. Here, a metal oxide heterojunction transistor (HJ‐TFT) sensor is developed for the label‐free, rapid detection of uric acid (UA) and 25(OH)Vitamin‐D3 (Vit‐D3) in human saliva. The HJ‐TFTs utilize a solution‐processed In2O3/ZnO channel functionalized with uricase enzyme and Vit‐D3 antibody for the selective detection of UA and Vit‐D3, respectively. The ultra‐thin tri‐channel architecture facilitates strong coupling between the electrons transported along the buried In2O3/ZnO heterointerface and the electrostatic perturbations caused by the interactions between the surface‐immobilized bioreceptors and target analytes. The biosensors can detect a wide range of concentrations of UA (from 500 nm to 1000 µM) and Vit‐D3 (from 100 pM to 120 nm) in human saliva within 60 s. Moreover, the biosensors exhibit good linearity with the physiological concentration of metabolites and limit of detections of ≈152 nm for UA and ≈7 pM for Vit‐D3 in real saliva. The specificity is demonstrated against various interfering species, including other metabolites and proteins found in saliva, further showcasing its capabilities.

Background: Primary Aldosteronism (PA) is a common subtype of hypertension that increases the risk of adverse cardiovascular and kidney events. The impact of COVID-19 on patients with PA is not well understood.This study aimed to investigate the impact of COVID-19 on patients with PA and compare their outcomes with hypertensive patients with essential hypertension. Methods: A cohort study was conducted using data from the Trinetx platform, including 9,817,307 participants enrolled between January 1, 2020, and July 31, 2022. The study group consisted of participants who tested positive for PCR SARS-CoV-2. The primary outcome was critical care and all-cause mortality, while the secondary outcomes were major adverse cardiac events (MACE) or major adverse kidney events (MAKE). The study included 4814 patients with PA and 4814 hypertensive controls. Results: Patients with PA had a higher risk of critical outcomes than the hypertensive control group (adjusted hazard ratio [aHR] 1.14, p = 0.001). Moreover, they had higher risks of MACE (aHR 1.32, p

Context: Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA. Objective: To evaluate the influence of ACS on image–adrenal venous sampling (AVS) correlation and the postoperative results. Methods: This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image–AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis. Results: Sixty-five patients (26.4%) had ACS. The image–AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26–4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954–271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004–0.339), P = 0.004). Conclusion: PA patients with ACS have higher image–AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.

Abstract Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1–5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1–5) had the best predictive value. MSE slope 1–5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1–5 was a good predictor of postinfarct LV systolic impairment.

Abstract Background Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM. Methods We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up. Results Baseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping. Conclusions After a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM.

Abstract Ionic liquid salts (ILs) are generally recognized as additives in perovskite precursor solutions to enhance the efficiency and stability of solar cells. However, the success of ILs incorporation as additives is highly dependent on the precursor formulation and perovskite crystallization process, posing challenges for industrial‐scale implementation. In this study, a room‐temperature spin‐coated IL, n‐butylamine acetate (BAAc), is identified as an ideal passivation agent for formamidinium lead iodide (FAPbI3) films. Compared with other passivation methods, the room‐temperature BAAc capping layer (BAAc RT) demonstrates more uniform and thorough passivation of surface defects in the FAPbI3 perovskite. Additionally, it provides better energy level alignment for hole extraction. As a result, the champion n–i–p perovskite solar cell with a BAAc capping layer exhibits a power conversion efficiency (PCE) of 24.76%, with an open‐circuit voltage (Voc) of 1.19 V, and a Voc loss of ≈330 mV. The PCE of the perovskite mini‐module with BAAc RT reaches 20.47%, showcasing the effectiveness and viability of this method for manufacturing large‐area perovskite solar cells. Moreover, the BAAc passivation layer also improves the long‐term stability of unencapsulated FAPbI3 perovskite solar cells, enabling a T80 lifetime of 3500 h when stored at 35% relative humidity at room temperature in an air atmosphere.

Background Concomitant atrial fibrillation and end‐stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long‐term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis‐dependent population. Methods and Results An updated network meta‐analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all‐cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34–1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64–0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all‐cause death with the administration of VKAs, DOACs, or no anticoagulation. Conclusions For dialysis‐dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding β-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

The prevalence of patients with primary aldosteronism (PA) is about 5%–15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan.Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.

Adrenal venous sampling (AVS) is a crucial method for the lateralization of primary aldosteronism (PA). It is advised to halt the use of the patient's antihypertensive medications and correct hypokalemia prior to undergoing AVS. Hospitals equipped to conduct AVS should establish their own diagnostic criteria based on current guidelines. If the patient's antihypertensive medications cannot be discontinued, AVS can be performed as long as the serum renin level is suppressed. The Task Force of Taiwan PA recommends using a combination of adrenocorticotropic hormone stimulation, quick cortisol assay, and C-arm cone-beam computed tomography to maximize the success of AVS and minimize errors by using the simultaneous sampling technique. If AVS is not successful, an NP-59 (131 I-6-β-iodomethyl-19-norcholesterol) scan can be used as an alternative method to lateralize PA. We depicted the details of the lateralization procedures (mainly AVS, and alternatively NP-59) and their tips and tricks for confirmed PA patients who would consider to undergo surgical treatment (unilateral adrenalectomy) if the subtyping shows unilateral disease.

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45–65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45–65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45–65: 14.5, >65: 31.6 %; p 65, mean difference, 77.8 m [95% confidence interval (CI), 2.1–153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37–15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45–65, mean difference, −2.1 mmHg [95% CI, −3.9 to −0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45–65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials. Objectives: We aim to investigate the change in global longitudinal strain (GLS) of A97S ATTR-CM patients after 12 months of tafamidis treatment. Methods: We retrospectively analysed a prospective cohort of patients with A97S ATTR-CM who received tafamidis meglumine (61 mg/day) at the National Taiwan University Hospital. Echocardiography with speckle tracking strain analysis was performed at baseline and 12 months after treatment. Results: In all, 20 patients were included in the cohort. The baseline left ventricular ejection fraction (LVEF) and interventricular septum (IVS) thickness were 59.20 ± 13.23% and 15.10 ± 3.43 mm, respectively. After 12 months of tafamidis treatment, the LVEF and IVS were 61.83 ± 15.60% ( p = 0.244) and 14.59 ± 3.03 mm ( p = 0.623), respectively. GLS significantly improved from −12.70 ± 3.31% to −13.72 ± 3.17% ( p = 0.048), and longitudinal strain (LS) in apical and middle segments significantly improved from −16.05 ± 4.82% to −17.95 ± 3.48% ( p = 0.039) and −11.89 ± 4.38% to −13.58 ± 3.12% ( p = 0.039), respectively. Subgroup analysis showed that patients with LVEF

Background Hereditary transthyretin amyloid cardiomyopathy (hATTR‐CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR‐CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium‐99m‐pyrophosphate in individuals diagnosed with hATTR‐CM. Methods and Results We retrospectively analyzed a prospective cohort from the NEURO‐TTRansform trial, including patients with hATTR‐CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR‐CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium‐99m‐pyrophosphate single‐photon emission computed tomography/computed tomography was conducted at baseline and during follow‐up. Thirteen patients with hATTR‐CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow‐up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (−20.7% versus −3.4%, P=0.007). Conclusions The volumetric heart and lung ratio used to quantify technetium‐99m‐pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR‐CM. These findings suggest the potential efficacy of eplontersen in treating hATTR‐CM and highlight the value of technetium‐99m‐pyrophosphate single‐photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Purpose: Mineralocorticoid receptor antagonists are the first-line treatment for bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA), while unilateral adrenalectomy is the standard treatment for aldosterone-producing adenoma (APA). In this study, we investigated the outcomes of patients with BAH after unilateral adrenalectomy and compared them with those of patients with APA. Methods: From January 2010 to November 2018, 102 patients with a diagnosis of PA confirmed by adrenal vein sampling (AVS) and available NP-59 scans were enrolled. All patients underwent unilateral adrenalectomy based on the lateralization test results. We prospectively collected the clinical parameters over 12 months and compared the outcomes of BAH and APA. Results: A total of 102 patients were enrolled in this study: 20 (19.6%) had BAH and 82 (80.4%) had APA. Significant improvements in serum aldosterone-renin ratio (ARR), potassium level, and reduction of antihypertensive drugs were observed in both groups at 12 months after surgery (all p

A mismatch between quasi-Fermi level splitting and open-circuit voltage is detrimental to wide bandgap perovskite pin solar cells. Here, through theoretical and experimental approaches, the authors optimize n- and p-type interfaces to achieve open-circuit voltage of 1.29 V and T80 of 3500 h at 85 °C.

Abstract Transthyretin cardiomyopathy (ATTR‐CM) is an under‐recognized cause of heart failure, but it has received increasing attention due to the availability of treatment options. We present a case of hereditary transthyretin cardiomyopathy (A97S, an under‐represented variant in current clinical studies) who presented with heart failure. Timely diagnosis and intervention with tafamidis demonstrated reversed cardiac remodelling via multiple imaging techniques (echocardiography, cardiac magnetic resonance imaging and technetium‐99m pyrophosphate scintigraphy). The echocardiography and cardiac magnetic resonance imaging demonstrated improved global strain. Cardiac magnetic resonance imaging showed decreased extracellular volume. The technetium‐99m pyrophosphate scintigraphy demonstrated decreased heart‐to‐contralateral ratio. This case highlights the potential reversible effect of tafamidis on A97S amyloidosis cardiomyopathy.

Background: Primary aldosteronism (PA) has been associated with atherosclerosis beyond the extent of essential hypertension, but the impact of albuminuria remains unknown. Objective: To investigate the effect of concomitant albuminuria on arterial stiffness in PA. Design: Prospective cohort study. Methods: A prospective cohort study was conducted to evaluate the association of albuminuria (>30 mg/g in morning spot urine) with arterial stiffness, as measured non-invasively by pulse wave velocity (PWV) in patients with PA. Propensity score matching (PSM) with age, sex, diabetes, systolic and diastolic blood pressure, creatinine, potassium, number of antihypertensive medications, and hypertension history was used to balance baseline characteristics. The effects of albuminuria on PWV before and 1 year after treatment were analyzed. Results: A total of 840 patients with PA were enrolled, of whom 243 had concomitant albuminuria. After PSM, there were no significant differences in baseline demographic parameters except alpha-blocker and spironolactone use. PWV was greater in the presence of albuminuria ( p = 0.012) and positively correlated with urine albumin–creatinine ratio. Multivariable regression analysis identified albuminuria, age, body weight, systolic blood pressure, and calcium channel blocker use as independent predictors of PWV. As for treatment response, only PA patients with albuminuria showed significant improvements in PWV after PSM ( p = 0.001). The magnitude of improvement in PWV increased with urine albumin–creatinine ratio and reached plateau when it exceeded 100 mg/g according to restricted cubic spline analysis. Conclusion: Concomitant albuminuria in PA was associated with greater arterial stiffness and more substantial improvement after targeted treatment. Both the baseline and the improved extent of PWV increased in correlation with rising urine albumin–creatinine ratio levels, reaching a plateau when the urine albumin–creatinine ratio surpassed 100 mg/g.

Abstract Objective Late‐onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is often associated with heart involvement. Recent advances in cardiac imaging allow the detection of cardiac amyloidosis. This study aimed to explore cardiomyopathy by cardiac imaging and its clinical correlates with polyneuropathy in late‐onset ATTRv‐PN. Methods Polyneuropathy was assessed by intraepidermal nerve fiber (IENF) density, nerve conduction study (NCS), autonomic function tests, quantitative sensory testing, and clinical questionnaires. Cardiomyopathy was evaluated by echocardiography, 99mTc‐pyrophosphate (PYP) single‐photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum Pro‐B‐type natriuretic peptide. Healthy controls and patients with Brugada syndrome were enrolled for comparison of CMR. Results Fifty late‐onset ATTRv‐PN patients (38 men, 46 with p. A117S mutation), aged 63.7 ± 5.5 years, of polyneuropathy disability stage 1–4 were enrolled. All patients presented polyneuropathy in NCS, and 74.5% of patients had reduced IENF density in distal legs. All patients showed significant radiotracer uptake in the heart on 99mTc‐PYP SPECT imaging, and 87.8% of patients had abnormally increased left ventricular (LV) septum thickness on echocardiography. CMR showed longer myocardial native T1, larger extracellular volume, greater LV mass index, and higher LV mass to end‐diastolic volume ratio in ATTRv‐PN patients than healthy controls and patients with Brugada syndrome. These CMR parameters were associated with skin denervation, absent sympathetic skin responses, elevated thermal thresholds, worsened NCS profiles, and functional deficits of polyneuropathy. Interpretation Late‐onset ATTRv‐PN coexisted with cardiomyopathy regardless of the clinical severity of polyneuropathy. The cardiac amyloid burden revealed by CMR was correlated with pathophysiology and clinical disability of nerve degeneration.

Abstract Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone‐producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug‐resistant hypertension, hypertensive with spontaneous or diuretic‐induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first‐degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well‐established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.

Charge carrier mobility is a fundamental property of semiconductors. The authors of this study demonstrate a novel way to estimate long-range mobilities of perovskite thin-films and single crystals by taking early-time carrier dynamics into account.

Abstract We performed the present study to investigate the role of computed tomography (CT) radiomics in differentiating nonfunctional adenoma and aldosterone-producing adenoma (APA) and outcome prediction in patients with clinically suspected primary aldosteronism (PA). This study included 60 patients diagnosed with essential hypertension (EH) with nonfunctional adenoma on CT and 91 patients with unilateral surgically proven APA. Each whole nodule on unenhanced and venous phase CT images was segmented manually and randomly split into training and test sets at a ratio of 8:2. Radiomic models for nodule discrimination and outcome prediction of APA after adrenalectomy were established separately using the training set by least absolute shrinkage and selection operator (LASSO) logistic regression, and the performance was evaluated on test sets. The model can differentiate adrenal nodules in EH and PA with a sensitivity, specificity, and accuracy of 83.3%, 78.9% and 80.6% (AUC = 0.91 [0.72, 0.97]) in unenhanced CT and 81.2%, 100% and 87.5% (AUC = 0.98 [0.77, 1.00]) in venous phase CT, respectively. In the outcome after adrenalectomy, the models showed a favorable ability to predict biochemical success (Unenhanced/venous CT: AUC = 0.67 [0.52, 0.79]/0.62 [0.46, 0.76]) and clinical success (Unenhanced/venous CT: AUC = 0.59 [0.47, 0.70]/0.64 [0.51, 0.74]). The results showed that CT-based radiomic models hold promise to discriminate APA and nonfunctional adenoma when an adrenal incidentaloma was detected on CT images of hypertensive patients in clinical practice, while the role of radiomic analysis in outcome prediction after adrenalectomy needs further investigation.

BackgroundPrimary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which KCNJ5 somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of KCNJ5 somatic mutations on systemic organ damage.Evidence acquisitionPubMed literature research using keywords combination, including “aldosterone-producing adenoma,” “somatic mutations,” “KCNJ5,” “organ damage,” “cardiovascular,” “diastolic function,” “metabolic syndrome,” “autonomous cortisol secretion,” etc.ResultsAPA patients with KCNJ5 somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of KCNJ5 somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery.ConclusionKCNJ5 somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without KCNJ5 mutations.

Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L‐FABP [liver‐type fatty‐acid binding protein], KIM‐1 [kidney injury molecule‐1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine‐corrected parameters, including L‐FABP, KIM‐1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L‐FABP/creatinine, KIM‐1/creatinine, creatinine‐based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P

Background: Elevated arterial stiffness in patients with primary aldosteronism (PA) can be reversed after adrenalectomy; however, the effect of medical treatment with mineralocorticoid receptor antagonist (MRAs) is unknown. Objectives: The aim of this study was to evaluate the effect of MRAs and compare both treatment strategies on arterial stiffness in PA patients. Design: Prospective cohort study. Methods: We prospectively enrolled PA patients from 2006 to 2019 who received either adrenalectomy or MRA treatment (spironolactone). We compared their baseline and 1-year post-treatment biochemistry characteristics and arterial pulse wave velocity (PWV) to verify the effects of treatment and related determinant factors. Results: A total 459 PA patients were enrolled. After 1:1 propensity score matching for age, sex and blood pressure (BP), each group had 176 patients. The major determinant factors of baseline PWV were age and baseline BP. The adrenalectomy group had greater improvements in BP, serum potassium level, plasma aldosterone concentration, and aldosterone-to-renin ratio. The MRA group had a significant improvement in PWV after 1 year of treatment (1706.2 ± 340.05 to 1613.6 ± 349.51 cm/s, p

Background: Primary aldosteronism (PA) is the leading cause of secondary hypertension globally and is associated with adverse cardiovascular outcomes. However, the cardiac impact of concomitant albuminuria remains unknown. Objective: To compare anatomical and functional remodeling of left ventricle (LV) in PA patients with or without albuminuria. Design: Prospective cohort study. Methods: The cohort was separated into two arms according to the presence or absence of albuminuria (>30 mg/g of morning spot urine). Propensity score matching with age, sex, systolic blood pressure, and diabetes mellitus was performed. Multivariate analysis was conducted with adjustments for age, sex, body mass index, systolic blood pressure, duration of hypertension, smoking, diabetes mellitus, number of antihypertensive agents, and aldosterone level. A local-linear model with bandwidth of 2.07 was used to study correlations. Results: A total of 519 individuals with PA were enrolled in the study, of whom 152 had albuminuria. After matching, the albuminuria group had a higher creatinine level, at baseline. With regard to LV remodeling, albuminuria was independently associated with a significantly higher interventricular septum (1.22 > 1.17 cm, p = 0.030), LV posterior wall thickness (1.16 > 1.10 cm, p = 0.011), LV mass index (125 > 116 g/m 2 , p = 0.023), and medial E/e′ ratio (13.61 > 12.30, p = 0.032), and a lower medial early diastolic peak velocity (5.70

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

Background: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. Methods: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. Results: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P

ObjectivePrimary aldosteronism (PA) is the most common type of secondary hypertension, and it is associated with a higher rate of cardiovascular complications. KCNJ5 somatic mutations have recently been identified in aldosterone-producing adenoma (APA), however their influence on vascular remodeling and injury is still unclear. The aim of this study was to investigate the association between KCNJ5 somatic mutation status and vascular status.MethodsWe enrolled 179 APA patients who had undergone adrenalectomy from a prospectively maintained database, of whom 99 had KCNJ5 somatic mutations. Preoperative clinical, biochemical and imaging data of abdominal CT, including abdominal aortic calcification (AAC) score, aortic diameter and wall thickness at levels of superior (SMA) and inferior (IMA) mesenteric arteries were analyzed.ResultsAfter propensity score matching for age, sex, body mass index, triglycerides and low-density lipoprotein, there were 48 patients in each KCNJ5 (+) and KCNJ5 (-) group. Mutation carriers had a lower AAC score (217.3 ± 562.2 vs. 605.6 ± 1359.1, P=0.018), higher aortic wall thickness (SMA level: 2.2 ± 0.6 mm vs. 1.8 ± 0.6 mm, P=0.006; IMA level: 2.4 ± 0.6 mm vs. 1.8 ± 0.7 mm, P

Background: Aldosterone excess in primary aldosteronism (PA) has been linked to insulin resistance, and diabetes mellitus has been associated with increased arterial stiffness and worse cardiovascular outcomes. However, the impact of diabetes on baseline and post-treatment arterial stiffness in patients with PA is unknown. Methods: This study prospectively enrolled 1071 PA patients, of whom 177 had diabetes and 894 did not. Clinical, biochemical, and brachial-ankle pulse wave velocity (baPWV) data were analyzed at baseline and 1 year after PA-specific treatment. After propensity score matching of age, sex, body mass index, systolic and diastolic blood pressure, hypertension duration, and number of antihypertensive medications, 144 patients with diabetes and 320 without diabetes were included for further analysis. Results: After propensity score matching, the baseline characteristics were balanced between the diabetes and nondiabetes groups except for fasting glucose, HbA1c, and lipid profiles. The patients with diabetes had significantly worse baseline baPWV compared with those without diabetes. After multivariable linear regression, the presence of diabetes mellitus remained a significant predictor of worse baseline mean baPWV (β: 46.3, 95% confidence interval: 2.9–89.7, p = 0.037). After 1 year of PA-specific treatment, only the nondiabetes group had significant recovery of mean baPWV (1661.8 ± 332.3 to 1565.0 ± 329.2 cm/s, p

Deregulation of redox homeostasis is often associated with an accelerated aging process. Ribose-5-phosphate isomerase A (RPIA) mediates redox homeostasis in the pentose phosphate pathway (PPP). Our previous study demonstrated that Rpi knockdown boosts the healthspan in Drosophila. However, whether the knockdown of rpia-1, the Rpi ortholog in Caenorhabditis elegans, can improve the healthspan in C. elegans remains unknown. Here, we report that spatially and temporally limited knockdown of rpia-1 prolongs lifespan and improves the healthspan in C. elegans, reflecting the evolutionarily conserved phenotypes observed in Drosophila. Ubiquitous and pan-neuronal knockdown of rpia-1 both enhance tolerance to oxidative stress, reduce polyglutamine aggregation, and improve the deteriorated body bending rate caused by polyglutamine aggregation. Additionally, rpia-1 knockdown temporally in the post-developmental stage and spatially in the neuron display enhanced lifespan. Specifically, rpia-1 knockdown in glutamatergic or cholinergic neurons is sufficient to increase lifespan. Importantly, the lifespan extension by rpia-1 knockdown requires the activation of autophagy and AMPK pathways and reduced TOR signaling. Moreover, the RNA-seq data support our experimental findings and reveal potential novel downstream targets. Together, our data disclose the specific spatial and temporal conditions and the molecular mechanisms for rpia-1 knockdown-mediated longevity in C. elegans. These findings may help the understanding and improvement of longevity in humans.

Introduction: Congenital left inferior vena cava (IVC) with hemiazygos continuation and drainage into the superior vena cava (SVC) is a rare IVC variant and is associated with venous thrombo-embolism. This is the report of a case of hemiazygos continuation of the left IVC receiving catheter directed thrombolysis (CDT) for pulmonary embolism. Report: A 72 year old woman presented with progressive dyspnoea, and CT images confirmed the diagnosis of pulmonary embolism. The unusual route of the IVC was observed during the right heart catherisation and CDT. CDT was then performed with a left femoral venous approach. The patient tolerated the procedure well, and the follow up pulmonary angiogram showed no residual thrombus. Discussion: The use of CDT for pulmonary embolism in patients with left IVC with hemiazygos continuation and drainage into the SVC has been reported rarely. Awareness of this diagnosis is critical during right heart catheterisation to prevent devastating complications. However, with careful manipulation, right heart catheterisation and CDT can be achieved successfully. Pulmonary embolism in patients with left IVC with hemiazygos continuation and drainage into the SVC can be treated with CDT safely and effectively with caution. It is wise to remember the different anatomical variations during IVC catheterisation.

Realizing phototransistors based on hybrid perovskite heterostructures with tuneable photodetection remains a challenge. Here, the authors integrate metal-halide perovskites into organic semiconductors to design hybrid heterojunction phototransistors with state-of-the-art performance.

The aim of this study was to analyze the differences in the distribution of abdominal adipose tissue between the two subtypes of primary aldosteronism (PA) using abdominal computed tomography. We retrospectively analyzed patients diagnosed as having essential hypertension (EH) or PA from the prospectively collected Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Patients with PA were divided into the subgroups of idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA). Patients’ basic clinicodemographic data were collected, and a self-developed CT-based software program was used to quantify the abdominal adiposity indexes, including visceral adipose tissue (VAT) area, VAT ratio, waist circumference (WC), subcutaneous adipose tissue (SAT) area, and SAT ratio. We included 190 patients with EH and 436 patients with PA (238 with IHA and 198 with APA). The APA group had significantly lower abdominal adiposity indexes than the other groups. We also found negative correlations of aldosterone-to-renin ratio (ARR) with VAT area, VAT ratio, WC, and body mass index (BMI) in the APA group. After propensity score matching (which left 184 patients each in the IHA and APA groups), patients in the APA group still had significantly lower WC, SAT area, SAT ratio, and VAT ratio than those in the IHA group. Furthermore, logistic regression analysis indicated that lower probability of abdominal obesity was significantly related to patients with APA. Our data revealed that the distribution of abdominal adipose tissue was similar in patients with IHA and those with EH, but the abdominal adiposity indexes were significantly lower in patients with APA than in those with IHA and EH.

BackgroundPrimary aldosteronism (PA) is a common cause of secondary hypertension and associated with higher incidence of new-onset atrial fibrillation (NOAF). However, the effects of surgical or medical therapies on preventing NOAF in PA patents remain unclear. The aim of this meta-analysis study was to assess the risk of NOAF among PA patients receiving mineralocorticoid receptor antagonist (MRA) treatment, PA patients receiving adrenalectomy, and patients with essential hypertension.MethodsWe performed the meta-analysis of the randomized or observational studies that investigated the incidence rate of NOAF in PA patients receiving MRA treatment versus PA patients receiving adrenalectomy from database inception until December 01, 2020 which were identified from PubMed, Embase, and Cochrane Library.ResultsA total of 172 related studies were reviewed, of which three fulfilled the inclusion criteria, including a total of 2,705 PA patients. The results of meta-analysis demonstrated a higher incidence of NOAF among the PA patients receiving MRA treatment compared to the PA patients receiving adrenalectomy (pooled odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.76–4.57 in the random effects model, I2 = 0%). The pooled OR for the PA patients receiving MRA treatment compared to the patients with essential hypertension was 1.91 (95% CI: 1.11–3.28). The pooled OR for the PA patients receiving adrenalectomy compared to the patients with essential hypertension was 0.70 (95% CI: 0.28–1.79).ConclusionCompared to the essential hypertension patients and the PA patients receiving adrenalectomy, the patients with PA receiving MRA treatment had a higher risk of NOAF.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021222022.

BackgroundSuperior outcomes after surgical treatment over medical treatment for primary aldosteronism (PA) has been reported in small-scale clinical studies, but no solid conclusion has been drawn as results of large randomized trials are lacking.MethodsWe performed a search of PubMed, MEDLINE, Embase and Cochrane Library for randomized or observational studies that investigated cardiovascular outcomes in patients with PA undergoing medical versus surgical treatment. Meta-analyses of both composite and individual outcomes were conducted. Risks of bias of the included studies were assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) checklist. Trial sequential analysis (TSA) was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.ResultsA total of 12 studies, including a total of 6148 PA patients, were included in the meta-analysis. The results of meta-analyses demonstrated lower incidence of composite cardiovascular outcomes among PA patients who underwent surgical treatment over medical treatment (odds ratio (OR): 0.49). Surgical treatment also led to less incidence of persistence of hypertension (OR of non-cure hypertension: 0.31). Fewer major cardiovascular events and mortality events were observed (OR: 0.60) after surgical treatment. TSA result showed that the required information size was 2151 and the cumulative Z curve crossed the futility boundary and reached the required information size.ConclusionSuperior performance of surgical treatment over medical treatment is confirmed with meta-analyses in terms of lower incidences of composite cardiovascular outcomes and non-cure of hypertension. Hence, adrenalectomy could now be concluded as the treatment of choice for lateralized PA.

ObjectivesPatients with primary aldosteronism (PA) have cardiac remodeling due to hemodynamic and non-hemodynamic causes. However, component analysis of cardiac remodeling and reversal in PA patients is lacking. We investigated components of cardiac remodeling and reversal after adrenalectomy in patients with aldosterone-producing adenoma (APA).MethodsThis study prospectively enrolled 304 APA patients who received adrenalectomy and 271 with essential hypertension (EH). Clinical, biochemical and echocardiographic data were collected in both groups and 1 year after surgery in the APA patients. The hemodynamic and non-hemodynamic components of left ventricular (LV) remodeling were represented by predicted left ventricular mass index (LVMI) (pLVMI) and inappropriately excessive LVMI (ieLVMI, defined as LVMI-pLVMI).ResultsAfter propensity score matching, 213 APA and 213 EH patients were selected. APA patients had higher hemodynamic (pLVMI) and non-hemodynamic (ieLVMI) components of LV remodeling than EH patients. In multivariate analysis, baseline pLVMI was correlated with systolic blood pressure (SBP) and serum potassium, whereas ieLVMI was correlated with log plasma aldosterone concentration but not blood pressure. Post-operative echocardiography was available in 207 patents and showed significant decreases in both pLVMI and ieLVMI after adrenalectomy. In multivariate analysis, ΔpLVMI was correlated with SBP, ΔSBP, and pre-operative pLVMI, whereas ΔieLVMI was correlated with Δlog aldosterone-to-renin ratio (ARR) and pre-operative ieLVMI.ConclusionsThis study concluded that extensive cardiac remodeling in APA patients occurs through hemodynamic and non-hemodynamic causes. Adrenalectomy can improve both hemodynamic and non-hemodynamic components of LV remodeling. Regressions of pLVMI and ieLVMI were correlated with decreases in blood pressure and ARR, respectively.

Background: The urinary sodium potassium (NaK) ratio is associated with dietary sodium and potassium intake and blood pressure, and it also reflects the activity of aldosterone. Herein we evaluated the value of the urinary NaK ratio in predicting the surgical outcomes of patients with unilateral primary aldosteronism (uPA). Methods: This non-concurrent prospective cohort study was conducted from 2011 to 2017 and included 241 uPA patients who had undergone adrenalectomy. Predictors of successful clinical outcomes were analyzed using logistic regression. Results: Among the 241 uPA patients, 197 (81.7%) achieved clinical complete or partial success. A urinary sodium potassium ratio 115 mmHg (OR: 5.02; 95% CI: 2.10–11.97; p

Background: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. Methods: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) 50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. Conclusions: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

Background/Purpose: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. Results: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the ‘gold standard’ of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. Conclusion: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care. Keywords: Primary aldosteronism, Guideline, TAIPAI

Background Primary aldosteronism (PA) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation (NOAF) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF, and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P=0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P=0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF. However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.