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Current Heart Failure Reports Apr 2024Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in... (Review)
Review
PURPOSE OF REVIEW
Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion-loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and current trial evidence for different diuretic strategies and explore potential future directions of research.
RECENT FINDINGS
We will assess recent trials, including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF, and assess how these may influence current practice and future research. There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high-dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF.
Topics: Humans; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Quality of Life; Diuretics; Hospitalization
PubMed: 38300391
DOI: 10.1007/s11897-024-00644-2 -
Journal of the American College of... Apr 2024Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential.
OBJECTIVES
The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment.
METHODS
DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance.
RESULTS
Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70).
CONCLUSIONS
Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).
Topics: Aged; Humans; Middle Aged; Benzhydryl Compounds; Conservation of Water Resources; Diuresis; Diuretics, Osmotic; Glucosides; Heart Failure; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left; Water
PubMed: 38599715
DOI: 10.1016/j.jacc.2024.02.020 -
British Journal of Pharmacology Feb 2024Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways... (Review)
Review
Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways unaddressed by guideline-recommended therapy. While spironolactone is widely considered as the preferable fourth-line drug, its broad application is limited by its side effect profile, especially off-target steroid receptor-mediated effects and hyperkalaemia in at-risk subpopulations. Recent landmark trials have reported promising safety and efficacy results for a number of novel compounds targeting relevant pathophysiologic pathways that remain unopposed by contemporary drugs. These include the dual endothelin receptor antagonist, aprocitentan, the aldosterone synthase inhibitor, baxdrostat and the nonsteroidal mineralocorticoid receptor antagonist finerenone. Furthermore, the evidence base for consideration of catheter-based renal denervation as a safe and effective adjunct therapeutic approach across the clinical spectrum of hypertension has been further substantiated. This review will summarise the recently published evidence on novel antihypertensive drugs and renal denervation in the context of resistant hypertension.
Topics: Humans; Hypertension; Kidney; Antihypertensive Agents; Spironolactone; Mineralocorticoid Receptor Antagonists; Denervation
PubMed: 37715452
DOI: 10.1111/bph.16247 -
International Journal of Cancer Oct 2023Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is...
Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Sodium Chloride Symporter Inhibitors; Myocarditis; Cross-Sectional Studies; Retrospective Studies; Diuretics; Thiazides
PubMed: 37306521
DOI: 10.1002/ijc.34616 -
Current Heart Failure Reports Dec 2023With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing.... (Review)
Review
PURPOSE OF REVIEW
With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing. The TRED-HF trial confirmed that heart failure remission rather than complete recovery is typical in patients with dilated cardiomyopathy who respond to therapy. The present review outlines key points related to the management and knowledge gaps of this growing patient group, focusing on patients with non-ischaemic dilated cardiomyopathy.
RECENT FINDINGS
There is substantial heterogeneity among patients with normalized ejection fraction. The specific etiology is likely to affect the outcome, although a multiple-hit phenotype is frequent and may not be identified without comprehensive characterization. A monogenic or polygenic genetic susceptibility is common. Ongoing pathophysiological processes may be unraveled with advanced cardiac imaging, biomarkers, multi-omics, and machine learning technologies. There are limited studies that have investigated the withdrawal of specific heart failure therapies in these patients. Diuretics may be safely withdrawn if there is no evidence of congestion, while continued therapy with at least some disease-modifying therapy is likely to be required to reduce myocardial workload and sustain remission for the vast majority. Understanding the underlying disease mechanisms of patients with normalized ejection fraction is crucial in identifying markers of myocardial relapse and guiding individualized therapy in the future. Ongoing clinical trials should inform personalized approaches to therapy.
Topics: Humans; Biomarkers; Cardiomyopathy, Dilated; Cardiotonic Agents; Diuretics; Heart Failure; Stroke Volume; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 37999902
DOI: 10.1007/s11897-023-00636-8 -
Tropical Doctor Oct 2023Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to... (Review)
Review
Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to alleviate symptoms, which, however, do not actually cure many patients. The gradual loss of cardiac function is impeded but not halted by such complicated pharmacological therapy, which primarily includes angiotensin-converting enzyme inhibitors, beta-blockers and diuretics, and sometimes digoxin, aspirin, warfarin, and anti-arrhythmic agents. Patients may be advised to track their weight and modify their diuretic prescription accordingly to avoid fluid overload or dehydration as part of the treatment plan. Non-pharmacologic treatment options are routinely integrated to improve the management of somatic complaints. Yoga and specialized breathing exercises seem to help CCF patients improve their cardiorespiratory and autonomic system function, and also their quality of life. We present the evidence.
Topics: Humans; Yoga; Quality of Life; Heart Failure; Angiotensin-Converting Enzyme Inhibitors; Breathing Exercises; Diuretics
PubMed: 37321800
DOI: 10.1177/00494755231180633 -
European Journal of Heart Failure Sep 2023Both acetazolamide and sodium-glucose cotransporter 2 (SGLT2) inhibitors block sodium reabsorption in the proximal renal tubule primarily through inhibition of... (Review)
Review
Similarities and distinctions between acetazolamide and sodium-glucose cotransporter 2 inhibitors in patients with acute heart failure: Key insights into ADVOR and EMPULSE.
Both acetazolamide and sodium-glucose cotransporter 2 (SGLT2) inhibitors block sodium reabsorption in the proximal renal tubule primarily through inhibition of sodium-hydrogen exchanger isoform 3 (NHE3), but neither SGLT2 inhibitors nor acetazolamide produce a sustained natriuresis due to compensatory upregulation of sodium reabsorption at distal nephron sites. Nevertheless, acetazolamide and SGLT2 inhibitors have been used as adjunctive therapy to loop diuretics in states where NHE3 is upregulated, e.g. acute heart failure. Two randomized controlled trials have been carried out with acetazolamide in acute heart failure (DIURESIS-CHF and ADVOR). In ADVOR, acetazolamide improved physical signs of fluid retention, but this finding could not be explained by the modest observed diuretic effect. Acetazolamide did not produce a natriuresis in the DIURESIS-CHF trial, and in ADVOR, immediate effects on symptoms and body weight were not reported, and the drug had no effect on morbidity or mortality after 90 days. Three randomized controlled trials have been carried out with empagliflozin (EMPAG-HF, EMPA-RESPONSE-AHF and EMPULSE) in acute heart failure. The EMPULSE trial did not report effects on diuresis or in changes in physical signs of congestion during the first week of treatment, but in EMPAG-HF and EMPA-RESPONSE-AHF, empagliflozin had no effect of dyspnoea, urinary sodium excretion or body weight during the first 4 days. In the EMPULSE trial, empagliflozin improved health status at 15 days and reduced the risk of worsening heart failure events at 90 days, but these effects are similar in magnitude and time course to the early statistical significance on the risk of heart failure hospitalizations achieved within 14-30 days in the major trials of SGLT2 inhibitors in patients with chronic heart failure. Neurohormonal inhibitors produce this early effect in the absence of a diuresis. Additionally, in numerous randomized controlled trials, in-hospital diuretic intensification has not reduced the risk of major heart failure events, even when treatment is sustained. These findings, taken collectively, suggest that any immediate diuretic effects of acetazolamide and SGLT2 inhibitors in acute heart failure are not likely to influence the short- or long-term clinical course of patients.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Acetazolamide; Sodium-Hydrogen Exchanger 3; Diuretics; Sodium; Body Weight; Glucose; Diabetes Mellitus, Type 2
PubMed: 37403655
DOI: 10.1002/ejhf.2968 -
Endocrinology and Metabolism (Seoul,... Dec 2023Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to...
Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.
Topics: Humans; Hyperaldosteronism; Aldosterone; Hypertension; Mineralocorticoid Receptor Antagonists; Republic of Korea
PubMed: 37828708
DOI: 10.3803/EnM.2023.1789 -
Current Heart Failure Reports Apr 2024Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in... (Review)
Review
PURPOSE OF REVIEW
Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion-loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and the current trial evidence for different diuretic strategies and explore potential future directions of research.
RECENT FINDINGS
We will assess recent trials including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF amongst others, and assess how these may influence current practice and future research. There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF.
Topics: Humans; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Quality of Life; Diuretics; Hospitalization
PubMed: 38240883
DOI: 10.1007/s11897-024-00643-3 -
Neuroscience and Biobehavioral Reviews Nov 2023Preclinical and human studies suggest a role of aldosterone and mineralocorticoid receptor (MR) in addiction. This scoping review aimed to summarize (1) the relationship... (Review)
Review
Preclinical and human studies suggest a role of aldosterone and mineralocorticoid receptor (MR) in addiction. This scoping review aimed to summarize (1) the relationship between alcohol and other substance use disorders (ASUDs) and dysfunctions of the aldosterone and MR, and (2) how pharmacological manipulations of MR may affect ASUD-related outcomes. Our search in four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) indicated that most studies focused on the relationship between aldosterone, MR, and alcohol (n = 30), with the rest focused on opioids (n = 5), nicotine (n = 9), and other addictive substances (n = 9). Despite some inconsistencies, the overall results suggest peripheral and central dysregulations of aldosterone and MR in several species and that these dysregulations depended on the pattern of drug exposure and genetic factors. We conclude that MR antagonism may be a promising target in ASUD, yet future studies are warranted.
Topics: Humans; Aldosterone; Receptors, Mineralocorticoid; Spironolactone; Mineralocorticoid Receptor Antagonists
PubMed: 37858908
DOI: 10.1016/j.neubiorev.2023.105427