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Background: Obstructive sleep apnoea (OSA) is associated with hypertension, and OSA treatment can reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but with a modest mean effect size and vast heterogeneity among studies. The aim of this individual patient data (IPD) meta-analysis was to understand which OSA phenotypes could benefit the most in terms of BP reduction., Methods: A systematic review of randomised controlled trials that compared continuous positive airway pressure (CPAP) with either passive or active treatment was conducted. Studies were eligible if they included adult patients with OSA diagnosed by full polysomnography or cardiorespiratory polygraphy (defined as apnoea-hypopnoea index >5 events·h -1 ) and if BP was measured both before and after CPAP treatment., Results: In total, 36 parallel studies (n=9434 patients) were included. CPAP treatment was associated with BP reduction in patients with uncontrolled office SBP only, while BP was not reduced by CPAP in patients with controlled BP (SBP -2.6 versus 0 mmHg; p<0.0001; DBP -1.7 versus -1 mmHg; p=0.091). Differences were seen also when BP changes were compared between patients aged ≤60 versus >60 years after multiple imputation only (p=0.0127 for SBP and p=0.017 for DBP). No differences were seen in terms of BP reduction when comparing patients with/without severe nocturnal hypoxia., Conclusions: This IPD meta-analysis of the BP effects of OSA treatment with CPAP shows that OSA patients with uncontrolled BP at baseline benefit the most from CPAP therapy in terms of BP reduction. These results have important implications for the decision on how to best manage arterial hypertension associated with OSA., Competing Interests: Conflict of Interest: E.I. Schwarz reports grants from Löwenstein Medical AG, Philips and LUNGE Zürich. P.A. Cistulli reports grants or contracts from ResMed, ResMed Foundation and SomnoMed for the provision of grant funds or equipment for investigator-initiated research, consulting fees from ResMed (paid to institution), and SomnoMed, Signifier Medical, Bayer and Sunrise (paid to consultant), and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from SomnoMed (paid to speaker). L.F. Drager reports grants from FAPESP (Brazilian Funding Agency; grant 2019/23496-8) and consulting fees from ResMed (consultant for real-world data on PAP telemonitoring). C. Fava reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Menarini and Novartis. M.S.M. Ip reports grants from Li Ka Shing Foundation. T. Quinnell reports grants from the UK NIHR for the PAPMAT study, with payments to their institution only, fees for an educational talk on sleep apnoea at Cambridge University Medical School, and a consultancy agreement with Jazz Pharma UK Ltd that included services in return for registration, accommodation, travel and subsistence at the World Sleep Conference in Rome; T. Quinnell is the President and then Past President of the British Sleep Society (unpaid), and the Chair of the Sleep Apnoea Specialty Advisory Group for the British Thoracic Society, and is also the Director of their own company, TNQ Medical Ltd, where they conduct private medical work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2025. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Antihypertensives (AHD) can influence cerebral autoregulation (CA) and attenuate hypertrophic concentric remodelling of arterioles. The aim of this study was to examine the associations between AHD, CA and structural and functional properties of cerebral arteries., Methods: In this observational, cross-sectional study 115 volunteers were divided in group 1 (non-hypertensive) [n = 30]; group 2 (hypertensive with systolic blood pressure [SBP] < 140 and diastolic blood pressure [DBP] < 90 mmHg) [n = 54]; group 3 (hypertensive with SBP ≥ 140 or DBP ≥ 90 mmHg) [n = 31] and simultaneous measurements of systemic blood pressure (BP) and middle cerebral artery blood flow velocity (CBFV) were obtained from digital plethysmography and transcranial Doppler. Beat-to-beat, critical closing pressure (CrCP), resistance-area product (RAP) and autoregulation index (ARI) values were extracted by linear regression analysis of instantaneous BP and CBFV waveforms using computerised analysis. Pulsatility index (PI) was calculated and CO 2 reactivity was assessed by the breath-holding test., Results: Despite their higher RAP (1.7 [±0.7], p < 0.001) compared to groups 1 and 2, uncontrolled hypertensive using diuretics (p = 0.047) and α2-agonists (p = 0.009) had significantly lower PI. Impaired CO 2 reactivity was common between the two hypertensive groups (p = 0.008), however ARI, CrCP and CBFV did not differ between them and non-hypertensive individuals and also did not correlate with any AHD used., Conclusions: Unlike the RAP, PI does not seem to reflect the real cerebrovascular resistence resulting from chronic arterial remodelling. Despite impaired CO 2 reactivity, hypertensive have arterial tonus and CA comparable to non-hypertensive. Experimental studies involving an untreated hypertensive control group are required to robustly make definitive conclusions about these questions., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Introduction: Amyloidosis is a group of diseases characterized by the deposition of misfolded protein fragments, forming insoluble fibrils in organs and tissues. Transthyretin (ATTR) amyloidosis, particularly cardiac amyloidosis (CA), leads to myocardial stiffness and heart failure. Right ventricular (RV) involvement is common in CA, but assessing RV stiffness noninvasively is challenging. This study aimed to evaluate RV stiffness using shear wave elastography (SWE) and correlate the findings with clinical, laboratory, and echocardiographic parameters., Materials and Methods: In this prospective, single-center, cross-sectional study, 60 patients were divided into three groups: 20 with cardiac ATTR amyloidosis (ATTR-CM), 20 with non-cardiac ATTR amyloidosis (ATTR non-CM), and 20 healthy controls. Myocardial stiffness was measured using SWE in the free wall of the RV. Pearson's and Spearman's correlation coefficients were used for statistical analysis, with significance set at p < 0.05., Results: RV SWE values showed a strong positive correlation with functional class and a moderate correlation with BNP and troponin I levels. A significant negative correlation was found between RV SWE values and the 6-minute walk test distance. SWE also correlated with echocardiographic variables like interventricular septum thickness and RV basal diameter. An SWE cutoff of ≥ 4.6. kPa was associated with cardiac involvement, showing 65 % sensitivity and 76 % specificity., Conclusions: SWE is a valuable noninvasive technique for assessing RV stiffness in CA patients, correlating well with clinical and echocardiographic parameters. An RV SWE value of ≥ 4.6 kPa could aid in early detection of cardiac involvement in ATTR amyloidosis, improving diagnosis and management., Competing Interests: Declaration of competing interest This work was funded by Pfizer (application - ID 55925015) and approved by the ethics committee of InCor through a substantiated opinion (CAAE 27437019.5.0000.0068). The authors declare that the sponsorship did not influence the results or the interpretation of the data presented in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antihypertensive treatment (AT) is essential for preventing hypertension-related cognitive decline. The goals of this observational study were to compare cognitive performance (CP) between non-hypertensive (NH) volunteers and hypertensive patients and to evaluate the correlation between CP and antihypertensive drugs (AHD). Three groups were constituted: NH (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. To analyze the cognitive domains, a neuropsychological battery was applied and the raw performance values in these tests were transformed into z-scores. The domain was considered impaired if it presented a z-score below -1.5 SD. Compared to group 1, both groups of hypertensive were older (51 [ ± 12] years) and showed a worse CP in episodic memory (p = 0.014), language (p = 0.003) and processing speed (PS) [p = 0.05]. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were the most used AHD (46.3%, p = 0.01 [group 2] and 64.5%, p = 0.005 [group 3]) and showed correlations with PS. Linear regression models revealed a negative association of PS with the use of ACEi (β = -0.230, p = 0.004), but not with the use of ARB (β = 0.208, p = 0.008). The effect of AT on cognition appears to go beyond the search for lower blood pressure targets and also includes the mechanism of action of AHD on the brain, so that additional benefits may possibly be achieved with simple adaptations in the treatment regimen, particularly in patients without clinically manifest cognitive impairment., Competing Interests: Competing interests: The authors declare no competing interests. Consent for publication: All authors give their verbal consent. Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting, or dissemination plans of the research. Ethics approval and consent to participate: This study was approved by the Research Ethics Committee (CONEP - Plataforma Brasil) linked to the Brazilian Ministry of Health (CAAE: 10637712.4.0000.0068) and by the Ethics Committee for Analysis of Research Projects (CAPPesq) of INCOR. All the participants provided written informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: The role of plasma metanephrine in adrenal venous sampling (AVS) for assessing lateralization in primary aldosteronism (PA) requires further clarification., Objective: To evaluate the performance of plasma metanephrine in AVS for determining aldosterone lateralization in PA, with or without mild autonomous cortisol secretion (MACS)., Methods: Sequential AVS under cosyntropin stimulation was conducted in 58 consecutive patients with PA and indication for AVS. The selectivity index (SI) was assessed using plasma metanephrine (SIMN) and cortisol (SIC). The lateralization index (LI) for aldosterone was calculated using metanephrine (LIA/MN) and cortisol (LIA/C)., Results: Right SIMN was significantly higher than left SIMN (127.91 nmol/L [78.12, 239.12] vs. 46.16 nmol/L [26, 73.87]; p< 0.001). SIMN and SIC were strongly correlated in both the right adrenal vein (r=0.518, p< 0.001) and the left adrenal vein (r=0.435, p< 0.001). A SIMN > 6.45 demonstrated a sensitivity and specificity of 100%, outperforming the cut-off of 12 for identifying successful catheterization. Six cases with SIMN > 12 and SIC between 3 and 5 indicated that a SIC > 3 is sufficient for confirming successful cannulation. LIA/MN and LIA/C were significantly correlated (r=0.752, p< 0.001), with PA lateralization concordant in 93.1% of cases. Two discordant cases (unilateral PA by cortisol, bilateral by metanephrine) exhibited non-classical histology, which is associated with a higher risk of PA recurrence. MACS was identified in 15 out of 58 patients (25.86%) and generally did not influence AVS lateralization, except when aldosterone and cortisol were secreted by different adrenal lesions., Conclusion: Metanephrine was superior to cortisol after cosyntropin for assessing selectivity and equivalent to cortisol for lateralization. Moreover, MACS did not impact lateralization in AVS under cosyntropin in most cases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Increased cardiac after load and multiple non-hemodynamic stimuli implicate in adverse left ventricular remodeling (LVR). This is particularly identifiable in treatment-resistant and secondary hypertension contexts, like primary hyperaldosteronism (PA), however little data exists on post-treatment residual LVR in these individuals., Methods: Cardiac magnetic resonance (CMR) with T1 mapping were performed in 14 patients with treated PA matched with 15 treated patients with primary hypertension (PH) and 15 healthy individuals. Blood pressure (BP) control was defined as < 140 x 90mmHg., Results: Treated PA and PH patients had similar indexed left ventricular, extracellular matrix and intracellular masses (respectively 68 ± 12g/m2, 17 ± 3g/m2 and 52 ± 10g/m2 for PA vs 63 ± 18g/m2, 16 ± 5g/m2 and 47 ± 14g/m2 for PH, p > 0.05 for all), that were significantly higher than normal individuals (47 ± 8g/m2, 11 ± 2g/m2 and 36 ± 6g/m2, respectively, p < 0.05 for all). Patients with uncontrolled BP exhibited greater cardiomyocyte hypertrophy than those controlled (55 ± 11 g/m2 vs 43 ± 11 g/m2, p = 0.01), regardless of the cause of hypertension. PH individuals had strong correlations between BP measurements and LVR parameters of the CMR, while in PA correlations were weaker., Conclusions: In treated patients with PA and PH, CMR detected similar residual tissue LVR in both groups. Uncontrolled BP was more related to the observed LVR than to the etiology of hypertension. BP levels were more strongly correlated to CMR LVR parameters in PH than PA patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Reiser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: The outcomes related to cardiovascular risk (CVR) in patients with the nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids or oral contraceptive pills., Objectives: To analyze CVR by markers of atherosclerosis in females with the nonclassical form according to therapeutic options., Design and Setting: A cross-sectional study at a tertiary center., Patients and Methods: Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into group 1 (G1) (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day), group 2 (G2) (n = 19) treated with oral contraceptive pills, and group 3 (G3) (30 matched controls). CVR was analyzed through serum lipids, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), inflammatory cytokines levels, and quantitative image evaluations [pulse wave velocity (PWV), endothelial function by flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and visceral fat (VAT) by abdominal tomography]., Results: There were no statistically significant differences in BMI, HOMA-IR, high-density lipoprotein-cholesterol, or triglyceride levels among groups (P > .05). Serum interleukin 6 (IL-6) levels were higher in G1 than in G2 (P = .048), and interleukin 8 (IL-8) levels were higher in G1 than in G2/3 (P = .008). There were no statistically significant differences in VAT, PWV, FMD, or CIMT among groups (P > .05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes., Conclusion: Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and IL-8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction  The absence of standardized reporting for sleep medicine exams across different laboratories can lead to misinterpretation, diagnostic inconsistencies, and suboptimal treatment strategies. This document seeks to establish guidelines for the development of sleep study reports, covering recordings from studies of types 1 to 4, and represents the official position of Associação Brasileira do Sono (ABS; Brazilian Sleep Association) on the standardization of polysomnography (PSG) and cardiorespiratory polygraphies. Materials and Methods  The recommendations for the items to be reported in PSG records were developed by means of a Delphi study, comprised of two voting rounds. In each round, participants had to vote regarding the appropriateness of items to be reported in type-1 to -4 sleep studies, rating them as recommended , optional , or not recommended . The consensus threshold was set at 66% in each voting round, or 75% for the combined responses of recommended and optional . Results  The panel was comprised of 29 experts. After 2 voting rounds and subsequent deliberations by the steering committee, 352 items were included in the final set of recommendations. Consensus was achieved for 339 items (96.3%), of which 145 (41.2%) were classified as recommended , 154 as optional (43.8%), 35 as not recommended (9.9%), and 5 as not allowed (1.4%). No consensus was reached for 13 items (3.7%). The items recommended in this consensus are detailed in the main text. Conclusion  These guidelines provide comprehensive recommendations for reporting diagnostic tests in sleep medicine., Competing Interests: Conflict of Interests GNP is a shareholder at SleepUp Tecnologia em Saúde Ltda. (São Caetano do Sul, SP, Brazil). The other authors have no conflict of interests to declare., (Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction  The current document represents the official position of Associação Brasileira do Sono (ABS; Brazilian Sleep Association) on the application of different sleep studies and provides specific recommendations for the use of different types of polysomnography (PSG) and respiratory polygraphy. Materials and Methods  The present document was based on existing guidelines. The steering committee discussed its findings and developed recommendations and contraindications, which were refined in discussions with the advisory committee. Adaptations were made based on professional experience, pathophysiological knowledge, and theoretical reasoning, especially to cover topics not discussed in previous guidelines or to adapt recommendations to the context and current practices in Brazil. Results  A total of 55 recommendations were made, covering the following domains: professional requirements for the requisition and interpretation of sleep studies ( n  = 7); eligibility for different sleep studies ( n  = 9); diagnosis of sleep-disordered breathing (SDB; n  = 5); diagnosis of SDB in special conditions ( n  = 3); diagnosis of SDB in association with other sleep disorders and comorbidities ( n  = 3); sleep studies on the follow-up of patients with SDB ( n  = 9); sleep studies for positive air pressure titration ( n  = 3); diagnosis of other sleep disorders ( n  = 10); and sleep studies on other conditions ( n  = 6). Conclusion  The selection of the type of sleep study should be made carefully, considering resource constraints, clinical suspicion of moderate or severe obstructive sleep apnea (OSA), and individual patient needs, among other factors. It is crucial that health professionals receive appropriate training and board certification in sleep science, thus being able to determine the most suitable diagnostic method, understand their indications and limitations, and assure an accurate diagnosis for each patient., Competing Interests: Conflict of Interests GNP is a shareholder at SleepUp Tecnologia em Saúde Ltda. (São Caetano do Sul, SP, Brazil). The other authors have no conflict of interests to declare., (Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by elevated levels of low-density lipoprotein cholesterol (LDLc). The early diagnosis of FH can reduce unfavorable outcomes in this population, but genetic study is not available in all populations. This study aimed to evaluate new cardiovascular plasma markers (GDF-15, CXCL16, FABP3, FABP4, LIGHT, sCD14, ucMGP), as well as Lp(a) levels, in individuals genetically characterized for FH, classified according to treatment with statins., Methods: Sequencing was performed by next generation sequencing (NGS) for 17 ICs and by the Sanger method for 120 relatives. Lp(a) was measured by turbidimetry and the other cardiovascular markers by the multiplex method for Luminex ® . Statistical analyses were performed using the R Platform version 4.2.2 program., Results: 86 individuals carrying FH genetic variants and 51 non-carrier family members were identified. Lp(a) showed higher levels in the group with variants and was correlated to LDLc levels. FABP3 levels were higher in the group carrying variants using statins compared to the group without statins. The non-carrier group using statins showed higher levels of FABP4 compared to the carrier group using statins. The markers GDF-15, CXCL16, LGHT, sCD14 and ucMGP did not show a significant difference between groups, but GDF-15 and sCD14 were correlated to LDLc levels., Conclusions: Lp(a) and the new markers FABP3 e FABP4 are associated with FH, their levels are modulated by the use of statins, and they could be potential markers to assess the disease when genetic testing is not available., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01537-w., Competing Interests: Conflict of interestThe authors declared that they have no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Ambulatory blood pressure (ABP) monitoring is a widespread recommendation for the diagnosis and management of hypertension. Dynamic resistance training (DRT) and isometric handgrip training (IHT) have been recommended for hypertension treatment, but their effects on ABP have been poorly studied. Additionally, combined dynamic and isometric handgrip resistance training (CRT) could produce an additive effect that has yet to be tested. Thus, this randomized controlled trial was designed to evaluate the effects of DRT, IHT and CRT on mean ABP and ABP variability. Fifty-nine treated men with hypertension were randomly allocated to 1 of four groups: DRT (8 dynamic resistance exercises, 50% of 1RM, 3 sets until moderate fatigue), IHT (4 sets of 2 min of isometric handgrip at 30% of MVC), CRT (DRT + IHT) and control (CON - 30 min of stretching). Interventions occurred 3 times/week for 10 weeks, and ABP was assessed before and after the interventions. ANOVAs and ANCOVAs adjusted for pre-intervention values were employed for analysis. Mean 24-h, awake and asleep BPs did not change in either group throughout the study (all, P > 0.05). Nocturnal BP fall as well as the standard deviation, coefficient of variation and the average real variability of ABP also did not change significantly in either group (all, P < 0.05). Changes in all these parameters adjusted to the pre-intervention values were also similar among the four groups (all, p > 0.05). In treated men with hypertension, 10 weeks of DRT, IHT or CRT does not decrease ABP levels nor change ABP variability., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the School of Physical Education and Sport, University of São Paulo (CAAE process 2.870.688). The data collected for this study were registered at the Brazilian Clinical Trials (RBR-4fgknb at http://www.ensaiosclinicos.gov.br ). The participants were given oral and written information about the benefits and risks of the study prior to entering the study. All patients who agreed to participate signed a consent document., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are antidiabetic agents that effectively lower blood glucose levels in patients with Type 2 Diabetes Mellitus (T2DM). Beyond their glycemic control properties, SGLT2 inhibitors have demonstrated significant cardiovascular benefits, including reductions in major adverse cardiovascular events. However, the limitations of the pivotal trials investigating these outcomes have not been fully explored. This letter aims to critically assess the major randomized clinical trials that evaluated the cardiovascular effects of SGLT2 inhibitors, highlighting both their strengths and limitations.

Chagas disease (CD), a neglected tropical disease, is caused by infection by the protozoan Trypanosoma cruzi. One-third of CD patients develop cardiac disease (CARD), an inflammatory and fibrotic process that may progress to heart failure associated with reduced left ventricular ejection fraction (LVEF). The determinants of CD progression are still uncertain. In non-infectious conditions, the angiotensin-converting enzyme (ACE) functional insertion (I)/deletion (D) and type 1 angiotensin II receptor (AT1R) +1166A>C gene polymorphisms have been linked to clinical outcomes. In a Brazilian cohort of 402 patients with positive serology for CD, in a case-control study we used PCR for genotyping the ACE rs4646994 I/D and AGTR1 rs5182C>T, rs275653 -119C>T, rs2131127A>G and rs5186 +1166A>C polymorphisms to evaluate association with CARD and progression to heart failure. Patients were classified as non-CARD (stage A; 109), and mild (stage B1; 161) or severe (stage C; 132) CARD. The groups were compared using unconditional logistic regression analysis and adjusted for non-genetic covariates (age, gender, and trypanocidal treatment). ACE II genotype appeared less frequent in C patients (15% in C vs 20% in B1 and 27% in A). After covariate adjustments, the ACE D allele showed a borderline association with susceptibility to severe CARD (C vs A: OR = 1.9; P = 0.08). AGTR1 +1166AC genotype showed a borderline association with protection against the progression and severity of CARD (C vs A: OR = 0.6; P = 0.09; C vs B1: OR = 0.6; P = 0.07; C vs A + B1: OR = 0.6; P = 0.05). However, adjustments for multiple comparisons showed no association of ACE I/D and AGTR1 polymorphisms with susceptibility and severity of CARD. The rs275653/rs2131127/rs5186/rs5182 T/A/C/T haplotype was protective against progression to the severe form of CARD (C vs B1: OR = 0.3; P = 0.03). Moreover, patients with ACE II and AGTR1 rs5186 +1166AC genotypes presented higher LVEF%. In C patients, TNF serum levels were higher in ACE D carriers than in II genotype. Although limited in number, a cross-sectional observation suggests that C-stage patients treated with benznidazole years prior to administration of ACE inhibitors/AT1R antagonists show reduced TNF serum levels and improved LVEF%. Therefore, variants of ACE and AGTR1 genes may influence the outcome of Chagas' heart disease and should be explored in precision medicine. Further, pharmacotherapies may improve immunological abnormality and clinical outcome in CD patients. Altogether, these data support prospective studies of this cohort and replication in other cohorts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Protásio da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories: <50 mg/dL (cohort 1), 50-69.9 mg/dL (cohort 2), 70-99.9 mg/dL (cohort 3), 100-129.9 mg/dL (cohort 4), 130-159.9 mg/dL (cohort 5), and ≥ 160 mg/dL (cohort 6). Mortality data were obtained by linking patient records to death registries spanning the 15 years prior to the analysis. Weighted Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) for mortality outcomes along with their 95% confidence intervals (CIs). A total of 2,145,732 individuals with CAD (mean age 72 years, SD 13; mean LDL-C 87.7 mg/dL, SD 37.7) were included in the analysis. Over a 15-year follow-up period, 191,779 deaths (8.9%) were recorded. After propensity score matching, patients with LDL-C < 50 mg/dL (37.05% vs. 33.11%, HR 1.144, 95% CI 1.125-1.164, p < 0.0001), LDL-C 130-159.9 mg/dL (26.47% vs. 25.71%, HR 1.032, 95% CI 1.007-1.059, p = 0.0136), and LDL-C ≥ 160 mg/dL (26.29% vs. 24.38%, HR 1.121, 95% CI 1.082-1.163, p < 0.0001) demonstrated a higher risk of all-cause mortality compared to those with LDL-C 100-129.9 mg/dL. Conversely, patients with LDL-C 50-69.9 mg/dL (27.88% vs. 29.68%, HR 0.898, 95% CI 0.883-0.913, p = 0.0002) and LDL-C 70-99.9 mg/dL (26.21% vs. 27.84%, HR 0.908, 95% CI 0.893-0.923, p = 0.0057) exhibited a lower risk of all-cause mortality compared to the reference group (LDL-C 100-129.9 mg/dL). In conclusion, our findings suggest a U-shaped relationship between LDL-C levels and all-cause mortality in patients with CAD, where both very low (< 50 mg/dL) and high (≥ 130 mg/dL) LDL-C levels are associated with increased mortality risk. These results highlight the need for individualized LDL-C targets in managing patients with CAD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

17β-estradiol (E2) is an endogenous steroid hormone pivotal for the development of female secondary sexual characteristics and the maintenance of the female reproductive system. Its roles extend beyond these physiological functions, as E2 is employed in hormone replacement therapy to alleviate symptoms associated with menopause. Furthermore, E2 exhibits therapeutic potential in the management of osteoporosis, breast cancer, and various neurological and cardiovascular conditions, partly due to its anti-inflammatory effects via modulation of the MAPK/NFκB signaling pathway. Notwithstanding, the hydrophobic nature of E2 significantly hinders the formulation of efficacious delivery systems for its clinical deployment. Recent advances have highlighted nano-based delivery systems for E2 as a promising solution to this solubility challenge. This review critically examines contemporary nano-delivery strategies for E2, particularly emphasizing lipid and polymeric nanoparticle-based systems. These nanostructures are designed to enhance stability, biocompatibility, controlled release, and targeted delivery of E2, yet the selectivity of E2 delivery for therapeutic purposes remains an ongoing challenge. The novelty of this review lies in its focus on the advances in nano-based E2 delivery systems over the past decade, a topic not extensively covered in prior literature. We present a comprehensive analysis of the encapsulation of E2 within polymeric and lipid nanoparticles, underscoring the untapped potential of these strategies. This review identifies a significant research gap, advocating for intensified experimental investigations that could pave the way for the translation of nano-based E2 therapies from bench to bedside., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Assis Ramos, Ricardo-da-Silva, Macedo, Correia, Moreira, Löbenberg, Breithaupt-Faloppa and Bou-Chacra.)

Background: Patient's clinical characteristics, technical resources, center and operator volume, and operator experience and training are known variables impacting outcomes. Although international standards have been agreed to maximize the benefits of this therapy, regional and global differences still exist. Latin American information has not been updated in the last 10 years. This study aimed to analyze current information on operators, centers, and CA in Latin America., Methods: Observational, retrospective study collecting Latin American information on operators and centers participating in CA, and procedures performed in 2023, from January 1 to December 31., Results: Electrophysiologists 178 (18 countries). Mean age 46,8 ± 9,2 (28-74) years. Male 86,5%. AFib, VT, and cardioneuroablation were performed by 80,2%, 70,9%, and 35,5% of operators respectively. Centers 175 (17 countries). Private 79,4% and academic 44,0%. Low volume (< 50/year) represented 36,6% and 38,3% performed ≥ 100 ablations/year. Procedures 7.595 (8.284 arrhythmias, 17 countries, 134 centers, 76 electrophysiologists). Patients mean age 51,5 ± 19,3 (1-95) years, male 55,3%, and 77,5% had a structurally normal heart. RF was the energy in 95,6% of procedures, cryoablation in 4,7%, and PFA in 0,2%. The most frequently treated arrhythmias were AFib (28,2%), AVNRT (20,9%), APs (15,8%), and PVC/NSVT (8,3%). Global success and complication rates were 93,6% and 3,0%, respectively and mortality 0,05%., Conclusion: II LAHRS EP Registry brings new and interesting data related to EP in Latin America. Electrophysiologists showed acceptable levels of experience, skills, and qualification. Although centers revealed an under-ideal availability of infrastructure and technical resources, the results of CA were comparable to other registries worldwide., Competing Interests: Declarations Ethics approval This study was conducted retrospectively. No ethical approval was required. Informed consent Not applicable/not required. Conflict of interest The authors declares that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Colchicine has demonstrated efficacy in treating coronary artery disease, but its efficacy in peripheral artery disease (PAD) remains uncertain. This study aims to address this gap in knowledge., Methods: A retrospective cohort study was conducted using the TriNetX Network, selecting patients with lower limb PAD between January 1, 2011, and January 1, 2024. Colchicine users were matched 1:1 with non-users through propensity score matching, considering demographics, medical conditions, medications, and psychosocial factors. The primary outcome was a composite of major adverse cardiovascular and limb events (MACLE) - including lower limb amputation, revascularization for lower limb ischemia, acute myocardial infarction, ischemic stroke, and all-cause mortality - over a ten-year follow-up., Results: From 53,568 colchicine-treated and 1,499,969 untreated patients with lower limb PAD, 52,350 pairs were successfully matched. Over ten years, colchicine was associated with a significant reduction in MACLE (hazard ratio, [HR] 0.90, 95% CI 0.88-0.92, p < 0.001), any lower limb amputation (HR 0.84, 95% CI 0.75-0.94, p = 0.002), revascularization for lower limb ischemia (HR 0.85, 95% CI 0.82-0.88, p < 0.001), major adverse cardiovascular events (HR 0.93, 95% CI 0.91-0.95, p < 0.001), and all-cause mortality (HR 0.90, 95% CI 0.87-0.92, p < 0.001). It also result in a reduced risk of ischemic stroke (HR 0.95, 95% CI 0.92-0.98, p = 0.001), but not of acute myocardial infarction (HR 0.98, 95% CI 0.95-1.01, p = 0.24)., Conclusions: Colchicine significantly reduced major adverse cardiovascular and limb events in patients with lower limb PAD, supporting the need for further investigation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diabetes carries an increased risk of cardiovascular disease and thromboembolic events. Upon endothelial dysfunction, platelets bind to endothelial cells to precipitate thrombus formation; however, it is unclear which surface proteins regulate platelet-endothelium interaction. We and others have shown that peri/epicellular protein disulfide isomerase A1 (pecPDI) influences the adhesion and migration of vascular cells., Objectives: We investigated whether pecPDI regulates adhesion-related molecules on the surface of endothelial cells and platelets that influence the binding of these cells in hyperglycemia., Methods: Immunofluorescence was used to assess platelet-endothelium interaction in vitro, cytoskeleton reorganization, and focal adhesions. Hydrogen peroxide production was assessed via Amplex Red assays (ThermoFisher Scientific). Cell biophysics was assessed using atomic force microscopy. Secreted proteins of interest were identified through proteomics (secretomics), and targets were knocked down using small interfering RNA. Protein disulfide isomerase A1 (PDI) contribution was assessed using whole-cell PDI or pecPDI inhibitors or small interfering RNA., Results: Platelets of healthy donors adhered more onto hyperglycemic human umbilical vein endothelial cells (HUVECs). Endothelial, but not platelet, pecPDI regulated this effect. Hyperglycemic HUVECs showed marked cytoskeleton reorganization, increased H 2 O 2 production, and elongated focal adhesions. Indeed, hyperglycemic HUVECs were stiffer compared with normoglycemic cells. PDI and pecPDI inhibition reversed the abovementioned processes in hyperglycemic cells. A secretomics analysis revealed 8 proteins secreted in a PDI-dependent manner by hyperglycemic cells. Among these, we showed that genetic deletion of LAMC1 and SLC3A2 decreased platelet-endothelium interaction and did not potentiate the effects of PDI inhibitors., Conclusion: Endothelial pecPDI regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Increased arterial stiffness is independently associated with cardiovascular risk. Obstructive sleep apnea (OSA) and sleep duration (SDUR) may contribute to increased arterial stiffness, but it is unclear whether this association is modulated by gender. We aimed to evaluate the potential impact of gender in modulating the association of OSA and SDUR with arterial stiffness. Participants from the ELSA-Brasil study performed sleep assessments with portable polygraph to define OSA severity and SDUR by 1-week wrist actigraphy. Pulse wave velocity (PWV) was measured using a standard technique without access to the sleep data. We studied 1863 participants (42.2% male, age: 49±8 years, respiratory disturbance index (RDI): 9.9 (4.5-19.4) events/h, SDUR: 6.5 (5.9-7.1) hours, mean PWV: 7.3 ± 1.2 m/s). We found that men had higher PWV, higher frequency of diabetes, and higher blood pressure when compared to women. The regression analysis showed an independent association between increased RDI and PWV in men (ß: 0.007; 95% CI: 0.001-0.012), but not in women. In contrast, an independent association between SDUR and increased arterial stiffness was observed only in women (ß: 0.068; 95% CI: 0.002-0.134). In conclusion, the association of sleep disorders with arterial stiffness showed a distinct gender pattern depending on the sleep variable studied., Competing Interests: Author ContributionsL.F.C., R.B.S., and L. F. D. are the guarantors of the article, taking responsibility for the integrity of the work as a whole, from inception to published article. L. F. D., P. A. L., and I. M. B. were responsible for study design; all authors performed data collection; L.F.C., L. F. D., R. B. S., S. G. F., B. K. P., and A. N. A. were responsible for data analysis; L.F.C. and L. F. D. drafted the manuscript; and all authors critically reviewed the manuscript. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The aim of this study was to build and validate an artificial neural network (ANN) algorithm to predict sleep using data from a portable monitor (Biologix system) consisting of a high-resolution oximeter with built-in accelerometer plus smartphone application with snoring recording and cloud analysis. A total of 268 patients with suspected obstructive sleep apnea (OSA) were submitted to standard polysomnography (PSG) with simultaneous Biologix (age: 56 ± 11 years; body mass index: 30.9 ± 4.6 kg/m 2 , apnea-hypopnea index [AHI]: 35 ± 30 events/h). Biologix channels were input features for construction an ANN model to predict sleep. A k-fold cross-validation method (k=10) was applied, ensuring that all sleep studies (N=268; 246,265 epochs) were included in both training and testing across all iterations. The final ANN model, evaluated as the mean performance across all folds, resulted in a sensitivity, specificity and accuracy of 91.5%, 71.0% and 86.1%, respectively, for detecting sleep. As compared to the oxygen desaturation index (ODI) from Biologix without sleep prediction, the bias (mean difference) between PSG-AHI and Biologix-ODI with sleep prediction (Biologix-Sleep-ODI) decreased significantly (3.40 vs. 1.02 events/h, p<0.001). We conclude that sleep prediction by an ANN model using data from oximeter, accelerometer, and snoring is accurate and improves Biologix system OSA diagnostic precision., (© 2024. The Author(s).)

This protocol aims to demonstrate the surgical technique for transferring cloned pig embryos to the oviduct, a method widely used in the production of genetically modified pigs for biomedical research. Nine gilts underwent hormonal synchronization and laparotomy for the transfer of cloned embryos produced by somatic cell nuclear transfer (SCNT) at stages of up to 4 cells on day 2 to the oviduct. Gestational diagnosis was conducted via ultrasound examination 30 days post-transfer surgery. Six out of the nine operated gilts exhibited signs of pregnancy on ultrasound examination. However, as there was no progression in fetal development as assessed by echography, the gilts underwent necropsy at 60 days for the collection of biological material and assessment of the reproductive system. Adhesions were observed in the uterine horns, ovaries, and oviducts. From the uterine lumen of two of the euthanized gilts, one and four embryonic structures with gestational ages ranging between 12 to 20 days were obtained. Despite the absence of live piglets, likely attributed to the low-efficiency rate of transferring cloned pig embryos, which is influenced by various factors, including the number and quality of transferred embryos, the presented surgical technique proved to be rapid and safe.

Background: Arterial stiffness is associated with higher burden of atrial arrhythmias and worsening left atrial function (conduit and reservoir), even before dilation of this cavity. PACs: premature atrial contractions; cfPWV: carotid-femoral pulse wave velocity., Background: Increased arterial stiffness is currently an independent risk factor for atrial fibrillation, but the pathophysiological mechanisms of this arrhythmia remain an area of knowledge gap to be explored., Objectives: To investigate the existence of an association between arterial stiffness and the density of premature atrial contractions (PACs) in hypertensive individuals without atrial fibrillation., Methods: Cross-sectional study with hypertensive patients without diagnosed atrial fibrillation, who were studied with speckle-tracking echocardiography to assess left atrial (LA) strain and carotid-femoral pulse wave velocity (cfPWV) to assess arterial stiffness. All patients underwent 24h-ECG Holter and laboratory tests. Significance level was set at p<0.05., Results: Seventy participants from a single centre without overt cardiovascular disease were included. The cfPWV was correlated with higher density of PACs in 24h-Holter monitoring, independently of LV mass index (1.48 [1.08-2.03], p-value 0.005). Increased cfPWV was correlated with decreased LA strain values, with Spearman correlation coefficients of -0.27 (p-value 0.027) and -0.29 (p-value 0.018) for reservoir and conduit 2D Strain, respectively., Conclusions: In this study with hypertensive patients, it was possible to demonstrate an association between arterial stiffness and higher density of atrial arrhythmias. Furthermore, arterial stiffness was associated with lower left atrial strain values for reservoir and conduit functions.

Rheumatic heart disease is an immune disorder that may occur as a complication of rheumatic fever. Diagnosing the reactivation of rheumatic carditis is a challenge, particularly in older individuals. We report a 43-year-old woman who experienced recurrent rheumatic myocarditis. The diagnosis, treatment, and follow-up were enabled by the use of multimodal imaging techniques., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this article to disclose., (© 2024 The Authors.)

Background: Chest wall tumors are uncommon. The surgical objective is local disease control and the relief of symptoms. Due to the heterogeneity of cases, the great variety of reconstructions, size of resection, and clinical and surgical outcomes are still uncertain., Methods: Patients were submitted to sternectomies for tumors between 1997 and 2019. Oncological, and surgical characteristics were taken into consideration. The outcomes were related to the size of resection and classified into local and systemic complications. The authors used univariate and multivariate analyses to determine predictors of complications. Survival analysis and Kaplan-Meier curves were obtained., Results: Thirty resections were performed due to metastatic disease. Partial sternectomy was accomplished in 48.8 %, followed by subtotal in 40 %. Primary closure using Pectoralis major was performed in 48.8 %, and Latissimus dorsi in 35.5 %. Polypropylene mesh was used in 86.6 % of reconstructions. The prosthesis removal was necessary in 6.66 %. Respiratory failure was evidenced in 6.66 %. The resection area was a predictor of local and systemic complications (p = 0.0029; p = 0.0004 respectively) in univariate analysis. However, the size of resection was the only predictor of systemic complications regarding multivariate analysis (p = 0.014, 95 % CI 1.00‒1.07)., Conclusion: The size of the resection was related to systemic complications, and the mesh reconstruction resulted in a low percentage of prosthesis removal and respiratory failure. This suggests a high resistance to local issues and a low respiratory failure rate., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and objectives: Aortic valve replacement surgery (SAVR) remains a recommended indication, though its pre-surgical stratification is an ongoing challenge. Despite the widespread use of scores like the STS and EuroSCORE II, they have a number of limitations, while often neglecting structural parameters like left ventricular hypertrophy or left atrium volume. This study aimed to evaluate whether a new adaptation of the Généreux classification in the preoperative risk stratification of severe aortic stenosis (AS) is associated with the primary outcome, and to compare it with the original classification versus the traditional scores in short- and long-term follow-up. Methods: We conducted a retrospective, single-center study involving patients with confirmed severe AS who underwent SAVR. The new stratification categorized patients into three stages. Cox regression analyses were conducted to identify factors associated with mortality, with survival analysis performed using Kaplan-Meier curves. A p -value < 0.05 was considered statistically significant. Results: A total of 508 patients were included. Stage 3 patients had a lower median age (67 years). The median EuroSCORE II and STS scores were 2.75 and 2.62%, respectively ( p ≤ 0.001). Over a median follow-up of 81 months, 56 deaths occurred (11%). Kaplan-Meier curve analysis revealed significant differences in all-cause mortality among the three groups (HR 4.073, log-rank p ≤ 0.001). Multivariable analysis identified the three preoperative stages (HR 3.22, [95% CI 1.44-7.20], p = 0.004) and mean transaortic gradient (HR 0.96, [95% CI 0.92-0.99], p = 0.021) as independent variables of mortality. The original Généreux scale AUC was higher (AUC: 0.760, 95% CI: 0.692-0.829) compared to the modified Généreux scale (AUC: 0.758, 95% CI: 0.687-0.829). However, no statistical differences were found between the different scales. Conclusions: Preoperative three-stage classification and low transaortic gradient are factors associated with increased all-cause mortality in patients undergoing SAVR. The proposed staging system performed better in the mortality analysis than EuroSCORE II and STS and was similar to the original classification.

Introduction: Heart transplantation (HTx) has emerged as a pivotal intervention for end-stage heart failure, offering significant improvements in survival and quality of life. This manuscript elucidates the landscape of HTx across Latin America (LATAM) from its advent in 1968 through December 2022, shedding light on its evolution, current practices, and regional disparities., Methods: We distributed a structured questionnaire to the national coordinators or representatives of the Interamerican Council of Heart Failure and Pulmonary Hypertension, collating responses from 20 LATAM nations. This approach facilitated a comprehensive aggregation of regional HTx data., Results: A total of 12,374 HTx were performed in 166 centers across 16 LATAM countries, with Brazil, Argentina, and Colombia accounting for the majority of procedures. Pediatric transplants represented 9% of the total caseload, and combined organ transplants were reported in 62.5% of the participating countries, underscoring the complexity and breadth of transplant services in the region., Conclusion: Despite facing infrastructural and logistical challenges, LATAM has demonstrated a robust capacity to conduct high-complexity transplant procedures. The establishment of a structured, regional HTx registry is imperative to enhance data collection and analysis, which in turn can inform clinical decision-making and policy development, ultimately improving patient outcomes across the continent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Brain death (BD) and cold storage (CS) are critical factors that induce inflammation in donor kidneys, compromising organ quality. We investigated whether treating kidneys from BD rats with an inflammasome Nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor (MCC950) followed by CS could reduce kidney inflammation., Methods: BD rats were assigned to MCC950-treated or nontreated (NT) groups. Kidneys were evaluated immediately before CS (T0) and after 12 h (T12) and 24 h (T24) of CS. Mean arterial pressure, serum creatinine, gene/protein expression, and histology were evaluated., Results: At T0, MCC950 treatment did not affect mean arterial pressure but tended to reduce serum creatinine and ameliorated the histological score of acute tubular necrosis. However, MCC950 reduced NLRP3, caspase-1, interleukin (IL)-1β, IL-6, Kim-1, nuclear factor kappa B, tumor necrosis factor alpha, and caspase-3 gene expression while increasing IL-10 cytokine gene expression. After 12 h of CS, only the expression of the NLRP3 and caspase-1 genes decreased, and after 24 h of CS, no further changes in the gene expression profile were observed. The levels of the inflammasome proteins NLRP3, caspase-1, and IL-1β consistently decreased across all time points (T0, T12, and T24)., Conclusions: These findings suggest that MCC950 treatment holds promise for mitigating the proinflammatory state observed in kidneys after BD and CS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Thoracic ultrasound (TUS) is a tool that has become increasingly essential in the daily practice of thoracic medicine. Driven by the need to assess patients during the COVID-19 pandemic, there has been an increase in the use of point-of-care TUS, which has demonstrated several benefits, either as a complement to clinical decision-making for diagnosis or as a real-time guide for procedures, whether as a predictor or measure of treatment response. Here, we present a review of TUS, based on the most recent scientific evidence, from equipment and techniques to the fundamentals of pulmonary ultrasound, describing normal and pathological findings, as well as focusing on the management of lung disease and guidance for invasive thoracic procedures at the bedside. Finally, we highlight areas of perspective and potential lines of research to maintain interest in this valuable tool, in order to improve the diagnostic process and expand the treatment arsenal.

Background: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group., Methods: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage., Results: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001)., Conclusion: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Competing Interests: Conflict of interest: None.

Introduction: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients., Methods: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years., Results: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m 2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects., Conclusions: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Cell therapy using adipose-derived mesenchymal stem cells (ADSCs) shows great potential as a treatment for cardiovascular diseases., Objective: We conducted a systematic review to describe the safety and efficacy of ADSCs in ischemic heart disease., Methods: We searched PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS (from inception to March 2024) for clinical studies involving ADSCs in patients with ischemic heart disease. We excluded studies involving patients with other types of heart disease, studies using mesenchymal stem cells derived from other tissues, as well as ongoing studies. Two independent reviewers screened the retrieved citations, extracted relevant data, and assessed the risk of bias in the included trials, using the Cochrane Collaboration criteria modified by McMaster University and Methodological Index for Non-Randomized Studies (MINORS). We used a narrative synthesis to present the results., Results: Ten studies (comprising 29 publications) met our inclusion criteria, including 8 randomized controlled trials and 2 uncontrolled trials. No severe adverse events associated with ADSC therapy were reported. While most efficacy endpoints did not reach statistical significance, there were reports of improved ischemic area, functional capacity, symptoms, and contractility in patients treated with ADSCs., Conclusions: The findings from our review suggest that ADSC therapy is generally safe for patients with ischemic heart disease. However, further investigation is warranted to confirm its efficacy, particularly with larger clinical trials and in specific conditions where improvements in microcirculation may have a notable impact on clinical outcomes.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: 1 ) the impact on renal hemodynamics and tubuloglomerular feedback; 2 ) the natriuretic effects via proximal tubule Na + /H + exchanger NHE3 inhibition; 3 ) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; 4 ) the impact on erythropoiesis, not only in the context of local hypoxia but also systemic inflammation and iron regulation; 5 ) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; 6 ) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance, and stimulation of lipolysis and ketogenesis; 7 ) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and 8 ) the direct cardiac effects. The intricate interplay between renal, neurohumoral, metabolic, and cardiac effects underscores the complexity of SGLT2i actions and provides valuable insights into their therapeutic implications for HF and CKD. Furthermore, this review sets the stage for future research to evaluate the individual contributions of these mechanisms in diverse clinical settings.

Importance: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes., Objective: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients., Registration: The protocol was registered at PROSPERO: CRD42019146781., Information Sources and Search: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023., Study Selection and Data Collection: Prospective and intervention studies were selected., Statistical Analysis: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed., Results: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89)., Conclusions: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable., (© 2024. The Author(s).)

Background: Recent studies show Silent Myocardial Infarction (SMI) as a quite frequent event. However, regarding severe tertiary care patients that frequently present consequences of Coronary Artery Disease (CAD) and Left Ventricular Dysfunction (LVD), the occurrence of this manifestation is unexpected and its associated factors aren't clear in the literature., Aim: To compare clinical, laboratorial, ventricular and angiographic factors between silent and classical presentation of MI in patients with CAD and LVD., Methods: Patients with multivessel CAD with over 70 % obstructive lesions and LVD with EF less than 35 % were evaluated for MASS VI trial and later included in the present study. The ventricular function and coronary assessment were measured by echocardiography and SYNTAX score, respectively. The population was stratified in a SMI group and Clinically Manifested Myocardial Infarction (CMMI) group based on MI presentation for a comparison of medical parameters., Results: From 132 patients, 47 (35.6 %) were classified as SMI and 85 (64.4 %) as CMMI. No differences were observed between groups regarding age, sex, diabetes mellitus, SYNTAX score, or collateral circulation. Higher proportion of NYHA II classification, inferior wall MI and lower creatinine clearance were found in SMI group. After multivariate analysis, peripheral diabetic neuropathy (OR = 4.6 [1.1‒12.7] p = 0.032) and inferior wall MI (OR = 4.1 [1.5‒11.4] p = 0.007) were significantly associated with SMI., Conclusion: Peripheral diabetic neuropathy and inferior wall MI were associated with SMI presentation. Overall, associated factors tend to be similar comparing SMI and CMMI, but in the specific population of diabetic patients with chronic neuropathy a special care should be taken., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: This study aimed to determine the prevalence of anxiety and depression among patients with glaucoma compared to the average Brazilian prevalence (9.8% of anxiety and 5.8% of depression, according to the World Health Organization) and its correlation with the severity of the disease., Methods: This was a transversal, single-arm trial of patients from four glaucoma centers in São Paulo and Curitiba-Brazil. Patients comprised adults at least 18 years of age with glaucoma diagnosis under treatment for at least 6 months. All subjects of the study answered two questionnaires (PHQ-9 and GAD-7) to evaluate the presence of anxiety and depression, and the results were analyzed accordingly to clinical and demographic characteristics., Results: The protocol included a total of 210 patients. The average age was 61.6 ± 15.3 years, and the female gender was more common (68.86%). Primary open-angle glaucoma was the most common diagnosis (59.90%). The average IOP was 18.5 mmHg, and 1.5 anti-glaucoma drops were the mean treatment. The prevalence of depression and anxiety was 26.90 and 25.71%, respectively. Most patients with anxiety were classified as early glaucoma, while those with depression had severe glaucoma., Conclusion: This study found that the prevalence of anxiety and depression among patients with glaucoma is higher than in the general population in our country., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giacometti, Coelho, Iankilevich, Valentin, Ferreira, Balbino and Seixas.)

Objective: Talc pleurodesis is a widely used treatment option for malignant pleural effusion (MPE). However, the optimal form of administration remains controversial. Thus, we performed a systematic review and meta-analysis to assess the effectiveness of talc slurry (TS) in comparison with thoracoscopic talc insufflation/poudrage (TTI) for MPE treatment., Methods: We searched PubMed, EMBASE, and Cochrane Library databases for studies that compared TS with TTI in patients with MPE. We used a random-effects model with a 95% CI to pool the data. Heterogeneity was assessed with I2 statistics., Results: We included eight studies involving 1,163 patients, 584 of whom (50.21%) underwent TS. Pleurodesis failure rates were similar between the procedures (OR = 1.07; 95% CI: 0.56-2.06; p = 0.83; I2 = 62%); and 68% of patients (95% CI: 0.31-1.47; p = 0.33; I2 = 58%) had postoperative complications, which were lower in patients in the TS group than in the TTI group. In a subgroup analysis considering only randomized clinical trials, the failure rate was significantly lower in the TS treatment group (OR = 0.62; 95% CI: 0.42-0.90; p = 0.01; I2 = 0%). Similarly, dyspnea was less common in the TS group (OR = 0.74; 95% CI: 0.41-1.34; p = 0.32; I2 = 55%). Adverse effects were reported in 86 patients, and no significant difference was seen between the TS and TTI groups: empyema (OR = 1.43; 95% CI: 0.36-5.64; p = 0.86; I2 = 0%), pain (OR = 1.22 (95% CI: 0.67-2.21; p = 0.51; I2 = 38%), and pneumonia (OR = 1.15; 95% CI: 0.30-4.46; p = 0.86; I2 = 27%)., Conclusions: Our findings suggest that TS is an effective treatment for MPE, with no significant increase in adverse events. Results suggest equivalent efficacy and safety for both procedures.