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ESC Heart Failure May 2024In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations... (Review)
Review
In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.
PubMed: 38806171
DOI: 10.1002/ehf2.14857 -
Survey of Ophthalmology 2023A 10-year-old boy presented with headache, fever, left-sided ptosis, and right-sided forehead soft tissue swelling. There was no recent history of trauma or infection....
A 10-year-old boy presented with headache, fever, left-sided ptosis, and right-sided forehead soft tissue swelling. There was no recent history of trauma or infection. The patient had a large, fluctuant mass on the right side of his forehead, upgaze restriction, left-sided ptosis, and bilateral optic disk edema. Magnetic resonance imaging of the brain showed a frontal bone extradural fluid collection superficial to the superior sagittal sinus in keeping with an epidural abscess. There were multiple venous thromboses and thickening and enhancement of the dura, compatible with meningitis. There was right sphenoid sinusitis. This patient had Potts puffy tumor, a rare diagnosis associated with a forehead swelling from frontal bone osteomyelitis and subperiosteal abscess. It is seen in the pediatric population in association with sinusitis or trauma. Antibiotics, anticoagulation, and acetazolamide were initiated, and the epidural abscess was evacuated. The symptoms and signs resolved with treatment.
Topics: Male; Humans; Child; Epidural Abscess; Pott Puffy Tumor
PubMed: 36427561
DOI: 10.1016/j.survophthal.2022.11.005 -
European Heart Journal Oct 2023In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear.
METHODS
This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms.
RESULTS
On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805).
CONCLUSIONS
Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes.
CLINICALTRIALS.GOV IDENTIFIER
NCT03505788.
Topics: Humans; Acetazolamide; Creatinine; Heart Failure; Diuresis; Kidney; Acute Disease
PubMed: 37623428
DOI: 10.1093/eurheartj/ehad557 -
Neurosurgery Clinics of North America Jul 2024Idiopathic intracranial hypertension is defined by headaches and a decline in visual acuity due to increased intracranial pressure. Treatment options historically...
Idiopathic intracranial hypertension is defined by headaches and a decline in visual acuity due to increased intracranial pressure. Treatment options historically included weight loss, acetazolamide, and/or cerebrospinal fluid diversion surgery. Recent understanding of the contributions of dural venous sinus hypertension and stenosis has led to venous sinus stenting as a treatment option.
Topics: Humans; Acetazolamide; Cranial Sinuses; Intracranial Hypertension; Pseudotumor Cerebri; Stents
PubMed: 38782521
DOI: 10.1016/j.nec.2024.02.001 -
Current Heart Failure Reports Apr 2024Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a... (Review)
Review
PURPOSE OF REVIEW
Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy.
RECENT FINDINGS
Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.
PubMed: 38589570
DOI: 10.1007/s11897-024-00659-9 -
Expert Opinion on Therapeutic Targets 2023Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related... (Review)
Review
INTRODUCTION
Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO, HCO/H ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens.
AREAS COVERED
Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for α-CA, α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25-4.0 µg/mL for wild type and drug resistant strains, and of 0.007-2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE.
EXPERT OPINION
Targeting bacterial CAs from other pathogens, among which , , , serovar Typhimurium, , , , , , , , , , may lead to novel antibacterials devoid of drug resistance problems.
Topics: Humans; Carbonic Anhydrase Inhibitors; Acetazolamide; Sulfonamides; Carbonic Anhydrases; Bacteria; Anti-Bacterial Agents; Sulfanilamide; Structure-Activity Relationship
PubMed: 37747071
DOI: 10.1080/14728222.2023.2263914 -
Revue Medicale Suisse Oct 2023Acute heart failure is a leading cause of hospitalisations with an increasing economic and public health burden. Management of acute heart failure involves the use of... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute heart failure is a leading cause of hospitalisations with an increasing economic and public health burden. Management of acute heart failure involves the use of diuretics to treat congestion and improve morbimortality. Despite current guidelines, numerous patients maintain congestion and often leave the hospital setting with incomplete volume depletion, leading to an increased risk of rehospitalisation. A recent multicentric randomised controlled trial studied the administration of acetazolamide in addition to standard care with loop diuretics in the acute setting. There was a significantly faster decongestion, based on a pragmatic clinical score, with very few side effects.
Topics: Humans; Acetazolamide; Diuretics; Heart Failure; Drug-Related Side Effects and Adverse Reactions; Hospitalization
PubMed: 37878100
DOI: 10.53738/REVMED.2023.19.847.2002 -
Wilderness & Environmental Medicine Mar 2024To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for...
To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.
Topics: Humans; Altitude Sickness; Altitude; COVID-19; Consensus; Societies, Medical; COVID-19 Testing
PubMed: 37833187
DOI: 10.1016/j.wem.2023.05.013 -
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