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ESC Heart Failure Dec 2022Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a...
AIMS
Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide.
METHODS AND RESULTS
Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r = -0.35, P = 0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r = -0.54, P < 0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r = 0.19, P = 0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P < 0.001), as well as lower plasma ANP levels (P = 0.027).
CONCLUSIONS
Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.
Topics: Humans; Atrial Natriuretic Factor; Diuretics; Heart Failure; Valsartan; Vasopressins; Neurosecretory Systems
PubMed: 36043451
DOI: 10.1002/ehf2.14083 -
Circulation Nov 2023Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical...
BACKGROUND
Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, specifically for patients with HF with mildly reduced or preserved ejection fraction, is uncertain.
METHODS
In this prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we assessed the association between various nonfatal worsening HF events (those requiring hospitalization, urgent outpatient visits requiring intravenous HF therapies, and outpatient oral diuretic intensification) and rates of subsequent mortality. We further examined the treatment effect of dapagliflozin on an expanded composite end point of cardiovascular death, HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification.
RESULTS
In DELIVER, 4532 (72%) patients experienced no worsening HF event, whereas 789 (13%) had outpatient oral diuretic intensification, 86 (1%) required an urgent HF visit, 585 (9%) had an HF hospitalization, and 271 (4%) died of cardiovascular causes as a first presentation. Patients with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 [8-12] per 100 patient-years) than those without a worsening HF event (4 [3-4] per 100 patient-years) but similar to rates of subsequent death after an urgent HF visit (10 [6-18] per 100 patient-years). Patients with an HF hospitalization as a first presentation of worsening HF had the highest rates of subsequent death (35 [31-40] per 100 patient-years). The addition of outpatient diuretic intensification to the adjudicated DELIVER primary end point (cardiovascular death, HF hospitalization, or urgent HF visit) increased the overall number of patients experiencing an event from 1122 to 1731 (a 54% increase). Dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio, 0.72 [95% CI, 0.64-0.82]) and when analyzed as a part of an expanded composite end point of worsening HF or cardiovascular death (hazard ratio, 0.76 [95% CI, 0.69-0.84]).
CONCLUSIONS
In patients with HF with mildly reduced or preserved ejection fraction, worsening HF requiring oral diuretic intensification in ambulatory care was frequent, adversely prognostic, and significantly reduced by dapagliflozin.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.
Topics: Humans; Stroke Volume; Outpatients; Heart Failure; Benzhydryl Compounds; Heart Failure, Diastolic; Diuretics; Ventricular Function, Left
PubMed: 37632455
DOI: 10.1161/CIRCULATIONAHA.123.066506 -
Journal of the American Heart... Dec 2022Background We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use....
Background We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset enrolled in acute treatment trials within VISTA (Virtual International Stroke Trials Archive). A VCS was defined based on blood urea nitrogen-to-creatinine ratio. The primary end point was modified Rankin Scale score at 90 days. Primary analysis used generalized ordinal logistic regression over the mRS range, adjusted for Totaled Health Risks in Vascular Events score, onset-to-enrollment time, and thrombolytic use. Of 5971 eligible patients with stroke, 42% were taking diuretics at the time of hospitalization, and 44% were in a VCS. Patients in a VCS were older, had more vascular risk factors, were more likely taking diuretics, and had more severe strokes. Diuretic use was associated with both reduced chance of achieving a good functional outcome (odds ratio [OR], 0.57 [95% CI, 0.52-0.63]) and increased mortality at 90 days (OR, 2.30 [95% CI, 2.04-2.61]). VCS was associated with greater mortality 90 days after stroke (OR, 1.53 [95% CI, 1.33-1.76]). There was no evidence of effect modification among the 3 exposures of VCS, diuretic use, or hypokalemia in relation to outcome. Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.
Topics: Humans; Prospective Studies; Diuretics; Stroke; Fibrinolytic Agents; Logistic Models; Treatment Outcome; Thrombolytic Therapy
PubMed: 36515241
DOI: 10.1161/JAHA.122.026903 -
BioMed Research International 2019is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the...
is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na and K excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na-K-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF- and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process.
Topics: Animals; Antidiuretic Agents; Diuretics; Lamiaceae; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Sodium; Urinalysis; Urination
PubMed: 31886241
DOI: 10.1155/2019/6927374 -
European Journal of Heart Failure Jan 2021
Topics: Benzhydryl Compounds; Diuretics, Osmotic; Glucosides; Heart Failure; Humans; Sodium
PubMed: 33372343
DOI: 10.1002/ejhf.2086 -
Journal of General Internal Medicine Jun 2020Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed... (Review)
Review
BACKGROUND
Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time.
AIM
To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics.
DATA SOURCES
A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014).
STUDY SELECTION
Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded.
DATA EXTRACTION
Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted.
DATA SYNTHESIS
Ninety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent.
CONCLUSION
Thiazide diuretics have a small and clinically unimportant impact on FPG.
Topics: Antihypertensive Agents; Blood Glucose; Diuretics; Fasting; Humans; Hypertension; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors
PubMed: 32157653
DOI: 10.1007/s11606-020-05731-3 -
British Journal of Clinical Pharmacology May 2022By contrast with drugs inhibiting the renin-angiotensin-aldosterone system (RAAS), diuretics stimulate renin release by the kidneys. Although plasma aldosterone (PA) is... (Meta-Analysis)
Meta-Analysis Review
AIM
By contrast with drugs inhibiting the renin-angiotensin-aldosterone system (RAAS), diuretics stimulate renin release by the kidneys. Although plasma aldosterone (PA) is thought to be mainly regulated by RAAS activity, serum potassium has been shown to be an important factor in animal models and humans. Here we perform a systematic review and meta-analysis of randomised controlled trials (RCT) in hypertension investigating the effects of diuretic therapy on PA and the correlation of change in PA with that of potassium and blood pressure (BP).
METHODS
Three databases were searched: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Titles were first screened by title and abstract for relevance before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria.
RESULTS
A total of 1139 articles were retrieved, of which 42 met the prespecified inclusion/exclusion criteria. The average standardised difference in mean PA was similar for all classes of diuretic: thiazide/thiazide-like 0.299 (95% confidence interval [CI] 0.150, 0.447), loop 0.927 (0.37, 1.49), MRA/potassium-sparing 0.265 (0.173, 0.357) and combination 0.466 (0.137, 0.796), Q = 6.33, P = .097. In subjects untreated with another antihypertensive, there was a significant relationship between change in PA and change in systolic BP but no relationship with the change in potassium.
CONCLUSION
In RCTs of diuretic therapy in hypertension, there is an increase in PA with all classes of diuretic and no significant between-class heterogeneity. Change in PA is not related with potassium but correlates with the change in BP in subjects untreated with another antihypertensive medication.
Topics: Aldosterone; Antihypertensive Agents; Blood Pressure; Diuretics; Humans; Hypertension; Potassium; Thiazides
PubMed: 34820874
DOI: 10.1111/bcp.15156 -
Kardiologia Polska 2023Considering the pathophysiology and clinical presentation of heart failure, using diuretics or drugs with diuretic properties is indispensable for adequate management of...
Considering the pathophysiology and clinical presentation of heart failure, using diuretics or drugs with diuretic properties is indispensable for adequate management of heart failure patients. However, in clinical practice, fluid expansion is often undiagnosed, and diuretic therapy is not always adequately titrated. Today, several drug classes with diuretic properties are available in addition to classical thiazides, thiazide-like, and loop diuretics. The purpose of this short review is to discuss different ways to optimize diuretic therapy using currently available drugs. Several approaches are considered, including a combination of diuretics to obtain a sequential nephron blockade, use of a drug combining a blocker of the renin-angiotensin system (RAS) and an inhibitor of the metabolism of natriuretic peptides (ARNI), prescription of potassium binders to maintain and up-titrate RAS blockers and mineralocorticoid antagonists, and finally use of inhibitors of renal reabsorption of glucose through the sodium-glucose cotransporter 2 system. Optimal use of these various drug classes should improve the quality of life and reduce the need for hospital admissions and mortality in heart failure patients.
Topics: Humans; Diuretics; Quality of Life; Sodium Chloride Symporter Inhibitors; Heart Failure; Glucose
PubMed: 37718589
DOI: 10.33963/v.kp.97315 -
Cardiorenal Medicine 2023Fluid overload is present in two-thirds of critically ill patients with acute kidney injury and is associated with morbidity, mortality, and increased healthcare... (Review)
Review
BACKGROUND
Fluid overload is present in two-thirds of critically ill patients with acute kidney injury and is associated with morbidity, mortality, and increased healthcare resource utilization. Kidney replacement therapy (KRT) is frequently used for net fluid removal (i.e., net ultrafiltration [UFNET]) in patients with severe oliguric acute kidney injury. However, ultrafiltration has considerable risks associated with it, and there is a need for newer technology to perform ultrafiltration safely and to improve outcomes.
SUMMARY
Caring for a critically ill patient with oliguric acute kidney injury and fluid overload is one of the most challenging problems. Although diuretics are the first-line treatment for management of fluid overload, diuretic resistance is common. Various clinical practice guidelines support fluid removal using ultrafiltration during KRT. Emerging evidence from observational studies in critically ill patients suggests that both slow and fast rates of net fluid removal during continuous kidney replacement therapy are associated with increased mortality compared with moderate UFNET rates. In addition, fast UFNET rates are associated with an increased risk of cardiac arrhythmias. Randomized trials are required to examine whether moderate UFNET rates are associated with a reduced risk of hemodynamic instability, organ injury, and improved outcomes in critically ill patients. There is a need for newer technology for fluid removal in patients who do not meet traditional criteria for initiation of KRT. Emerging newer and miniaturized ultrafiltration devices may address an unmet clinical need.
KEY MESSAGES
Among critically ill patients with acute kidney injury and fluid overload requiring continuous kidney replacement therapy, use of higher and slower UFNET rates compared with moderate UFNET rates might be associated with poor outcomes. Newer minimally invasive technologies may allow for safe and efficient UFNET in patients with acute kidney injury who do not meet criteria for initiation of KRT.
Topics: Humans; Ultrafiltration; Critical Illness; Renal Replacement Therapy; Acute Kidney Injury; Diuretics
PubMed: 36202071
DOI: 10.1159/000527390 -
Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction.Cells Sep 2022Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote...
Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function-especially when strained-and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.
Topics: Animals; Fibrosis; Furosemide; Heart Failure; Mineralocorticoid Receptor Antagonists; Mitral Valve Insufficiency; Rats; Receptors, Mineralocorticoid; Spironolactone; Ventricular Remodeling
PubMed: 36078158
DOI: 10.3390/cells11172750