Heart failure with reduced ejection fraction (HFrEF) is a commonly seen clinical entity in the family physician\'s practice. This clinical review focuses on the pharmacologic management of chronic HFrEF. Special attention is paid to the classification of heart failure and the newest recommendations from the American Heart Association concerning the use of guideline-directed medical therapy. β blockers, ACE inhibitors, ARBs, mineralocorticoid receptor antagonists are discussed in detail. The new emphasis on sacubitril-valsartan and SGLT2i\'s as therapies for HFrEF are reviewed, followed by a brief discussion of more advanced therapies and comorbidity management.

UNASSIGNED: To compare the efficacy and safety of subthreshold micropulse laser (SML) and spironolactone therapy for treating chronic central serous chorioretinopathy (CSC).
UNASSIGNED: This was a quasi-randomized controlled trial. Eligible patients were quasi-randomized at a 1:1 ratio to receive SML or oral spironolactone and were assessed at 3 months after treatment.
UNASSIGNED: A total of 84 patients (90 eyes) were randomly assigned to receive SML (n = 45) or spironolactone (n = 39) initially. At last follow-up, 59.5% of patients in the SML group had complete resolution of subretinal fluid (SRF) compared to 43.6% in spironolactone group (P = 0.362). The mean visual acuity did not significantly improve between the two groups (0.38 ± 0.44 vs. 0.43 ± 0.43 logMAR). The central retinal thickness was decreased from 335.06 ± 120.25 µm to 222.15 ± 94.90 µm in the SML group and from 308.02 ± 90.69 µm to 257.27 ± 102.28 µm in the spironolactone group. After treatment, subfoveal choroidal thickness, total choroidal area, and stromal and luminal choroidal area were significantly lower in the spironolactone group as compared to the SML group. During the entire visit, the recurrence rate of SRF was 9.1% in the SML group compared to 35.3% in the spironolactone group. Slight adverse events occurred more frequently in the spironolactone group (0% vs. 16%).
UNASSIGNED: Both SML and oral spironolactone were effective and safe treatments to ameliorate retinal anatomical structures for chronic CSC. A lower recurrence rate and fewer adverse effects were observed in the SML group, and better choroidal structure recovery was seen in the spironolactone group.
UNASSIGNED: The investigation of SML and oral spironolactone may inform evidence-based clinical decisions for chronic CSC patients.

Cardio-Renal-Metabolic (CaReMe) diseases, in the form of heart failure, chronic kidney disease and diabetes mellitus, justify prescription of multiple prognostically beneficial medications, specifically renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 inhibitors. Use of these medications is complicated by association with adverse effects, particularly acute kidney injury and hyperkalaemia. Balancing risk and benefit is a common dilemma in acute medicine, with increasingly frequent and complex treatment decisions. Physicians should contemplate adjustments to medications within the context of not just acute illness but also long-term benefit. In the setting of hyperkalaemia, potassium-binding medications can be utilised. At hospital discharge optimisation of therapy can be achieved through clear safety netting advice, scheduled biochemical follow-up, and planned clinical review.

UNASSIGNED: Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking.
UNASSIGNED: The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay.
UNASSIGNED: A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group (P=0.028), and ΔTWV was 1.2±1.7 cm3 in the placebo group and 0.037±1.9 cm3 in the spironolactone group (P=0.022). Change in LV mass was 3.1±8.4 g in the placebo group and -5.8±8.4 g in the spironolactone group (P=0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of -10.1±36.3 ms in the spironolactone group; P=6.33×10-4). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation.
UNASSIGNED: Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis.
UNASSIGNED: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02169089.

OBJECTIVE: Esaxerenone, a mineralocorticoid receptor blocker, attenuates global ischemia-induced myocardial damage and coronary endothelial dysfunction. This study aimed to determine whether esaxerenone exerted cardioprotective effects against cardioplegic arrest in Wistar rat hearts.
METHODS: Isolated male Wistar rat hearts aerobically perfused via the Langendorff method for 20 min were randomly allocated to the Control (n = 6; perfused for an additional 10 min and subjected to no treatment) or Esax (n = 6; perfused with 0.1 μmol/L esaxerenone in perfusate for 10 min before ischemia) groups. Hearts in both groups were perfused with St. Thomas\' Hospital No. 2 solution (STH2) for 2 min and subjected to 28 min of global ischemia. The recovery of left ventricular developed pressure (LVDP) and total troponin T leakage were measured after reperfusion.
RESULTS: The final recovery of LVDP (expressed as a percentage of pre-ischemic value) in the Control and Esax groups was 50.8 ± 3.5% and 62.1 ± 5.6%, respectively (p <0.05, Esax vs. Control). The total troponin T leakage in the Control and Esax groups was 138.8 ± 18.5 ng/g heart wt and 74.3 ± 18.6 ng/g heart wt, respectively (p <0.05, Esax vs. Control).
CONCLUSIONS: The administration of esaxerenone before cardioplegic arrest enhanced the cardioprotective effect exerted by STH2.

暂无摘要。

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes.

UNASSIGNED: To evaluate the efficacy and safety of non-steroid mineralocorticoid receptor antagonists (ns-MRAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with diabetic kidney disease (DKD).
UNASSIGNED: Systematic literature searches were performed using PubMed, Embase and Web of Science encompassing inception until January 20, 2024. Randomized control trials (RCTs) comparing ns-MRAs and SGLT2is in DKD were selected. The efficacy outcomes of interest included kidney-specific composite outcome, cardiovascular (CV)-specific composite outcome, end-stage kidney disease (ESKD), and overall mortality. We also investigated safety outcomes, including acute kidney injury (AKI) and hyperkalemia.
UNASSIGNED: A total of 10 randomized clinical trials with 35,786 patients applying various treatments were included. SGLT2is (SUCRA 99.84%) have potential superiority in kidney protection. SGLT2is (RR 1.41, 95%CI 1.26 to 1.57) and ns-MRAs (RR 1.17, 95% CI 1.08 to 1.27) were associated with significantly lower kidney-specific composite outcome than the placebo. Regarding the reduction in CV-specific composite outcome and ESKD, SGLT2is (SUCRA 91.61%; 91.38%) have potential superiority in playing cardiorenal protection. Concerning the CV-specific composite outcome (RR 1.27, 95%CI 1.09 to 1.43) and ESKD (RR 1.43, 95%CI 1.20 to 1.72), SGLT2is significantly reduced the risks compared to placebo. Regarding the reduction in overall mortality, SGLT2is (SUCRA 83.03%) have potential superiority in postponing mortality. Concerning the overall mortality, SGLT2is have comparable effects (RR 1.27, 95%CI 1.09 to 1.43) with placebo to reduce the risk of overall mortality compared to placebo. For AKI reduction, ns-MRAs (SUCRA 63.58%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. For hyperkalemia reduction, SGLT2is (SUCRA 93.12%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. Concerning hyperkalemia reduction, nsMRAs (RR 1.24 95%CI 0.39 to 3.72) and SGLT2is (RR 1.01 95%CI 0.40 to 3.02) did not show significant benefit compared to placebo.
UNASSIGNED: Concerning the efficacy and safety outcomes, SGLT2is may be recommended as a treatment regimen for maximizing kidney and cardiovascular protection, with a minimal risk of hyperkalemia in DKD.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023458613.

UNASSIGNED: RENIN-ANGIOTENSINALDOSTERONE SYSTEM BLOCKADE AND BEYOND. Patients with chronic kidney disease (CKD) require both etiological and symptomatic treatments to slow renal function decline. Reductions of protein and salt intakes are required. Pharmacological treatments combines blockade of the renin-angiotensin system, sodium-glucose co-transporter type 2 inhibitors and mineralocorticoid receptor antagonists in most diabetic patients. The albumin creatinine ration (ACR) in morning spot urine samples is now a therapeutic target both in diabetic and non-diabetic CKD patients.
NÉPHROPROTECTION MÉDICAMENTEUSE : AU-DELÀ DU BLOCAGE DU SYSTÈME RÉNINE-ANGIOTENSINE. Au-delà du traitement étiologique éventuel d’une maladie rénale chronique (MRC), et du contrôle de l’ensemble des facteurs de risque vasculaire, un traitement symptomatique est nécessaire pour ralentir le déclin de la fonction rénale. La prise en charge diététique permet de limiter les apports en protéines et en sel. Le traitement pharmacologique comporte nécessairement une association d’un bloqueur du système rénine-angiotensine-aldostérone, le plus souvent un inhibiteur du co-transport sodiumglucose de type 2 (SGLT2i) et chez certains diabétiques un antagoniste des récepteurs des minéralocorticoïdes (ARM). Le rapport albuminurie/créatininurie (RAC) sur un échantillon d’urine devient une cible thérapeutique aussi bien chez les non-diabétiques que chez les diabétiques.