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JACC. Heart Failure Jun 2024The addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the...
BACKGROUND
The addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the diuretic response in patients with acute heart failure (AHF).
OBJECTIVES
This work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF).
METHODS
This post hoc analysis of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated.
RESULTS
The median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher natriuretic peptide levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all P values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all P values were insignificant).
CONCLUSIONS
Adding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], NCT01647932; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number 2013-001852-36).
PubMed: 38934966
DOI: 10.1016/j.jchf.2024.05.006 -
Cardiology in Review Jun 2024Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with...
Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with diuretic therapies without any significant mortality benefit. The underlying cause of TR can be primary, coming from structural issues with tricuspid valve and more commonly secondary, arising from conditions affecting the right ventricle or the pulmonary circulation. Management of TR has seen few improvements until recently. Traditionally, valve replacement and surgical repair were the therapeutic options available. Tricuspid valve is a complex cardiac structure with many technical challenges for surgical intervention. Transcatheter valve interventions have proven to be safe and effective novel therapeutic options for severe TR, which reduce the severity of TR with associated improvement in quality of life. In this review, we will provide an overview of the management of severe TR utilizing transcatheter edge-to-edge repair with the TriClip device (Abbott, Santa Clara, CA).
PubMed: 38934619
DOI: 10.1097/CRD.0000000000000740 -
European Journal of Emergency Medicine... Aug 2024
Topics: Humans; Heart Failure; Diuretics; Acute Disease; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38934074
DOI: 10.1097/MEJ.0000000000001151 -
Qatar Medical Journal 2024SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an...
BACKGROUND
SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function.
METHODS
We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes.
RESULTS
Two prospective observational studies, encompassing a total of 359 participants, of which 197 utilized SGLT2 inhibitors, were identified. Our findings indicated that the use of SGLT2 inhibitors during Ramadan did not result in a significant alteration in eGFR. In one study by Hassanein et al., the mean changes in eGFR for the SGLT2i group, as compared to the non-SGLT2i group, were -1.2 ± 19.4 and 3.1 ± 14.8, respectively ( = 0.06). In a study by Shao et al., the least squares mean changes for eGFR in the SGLT2i group, compared to the non-SGLT2i group, were -6.0 ± 1.5 (95% CI, -8.9 to -3.1) and -4.2 ± 1.6 (95% CI, -7.3 to -1.1), respectively ( = 0.39).
CONCLUSION
Despite the limited number of observational studies available, our analysis suggests that the use of SGLT2 inhibitors by type 2 diabetes patients during Ramadan does not appear to significantly impact kidney function.
PubMed: 38933780
DOI: 10.5339/qmj.2024.29 -
World Journal of Nuclear Medicine Jun 2024Technetium-99m ethylene dicysteine (Tc-99m EC) is a well-established, tubular tracer for diuretic renography. Few occasional cases have been reported in literature...
Technetium-99m ethylene dicysteine (Tc-99m EC) is a well-established, tubular tracer for diuretic renography. Few occasional cases have been reported in literature regarding visualization of liver, gallbladder (GB), or bowel due to increased hepatobiliary route of excretion of Tc-99m EC on diuretic renography. This study aimed to retrospectively review the incidence of visualization of liver, GB, or bowel and its clinical significance in Tc-99m EC diuretic renography. Data of all patients who underwent diuretic renography in the department from January 24, 2022 to March 31, 2023 was included in the study. The data was analyzed to assess the incidence of visualization of GB or bowel loops, correlation of the hepatobiliary localization with factors like age of the patient, concentration of 99m TcO4 solution, quality control parameters, presence of renal stone disease, serum creatinine, relative renal function, and effective renal plasma flow. Effect of hepatobiliary localization on scan interpretation and reporting was assessed. The retrospective analysis of 437 diuretic renograms revealed the hepatobiliary localization of tracer in 34 patients. Out of these 34 patients, 14 patients had only faint visualization of tracer at 4 hours delayed image. Twenty scans had visualization of both GB and bowel. Out of these 20 scans, GB and bowel were visualized during dynamic imaging in one scan, after initial 20 minutes in two scans and in 2 to 4 hours delayed images in rest of the 17 scans. Two out of 20 patients had increased serum creatinine, 16 patients had either single kidney or relative renal function less than 26%, and 12 patients had renal stone disease. Out of the four patients in whom relative renal function was more than 25%, one patient had raised serum creatinine and three patients had renal stone disease. Interpretation of images was affected only in three patients, in which reporting of the scans required single-photon emission computed tomography imaging and correlation with other imaging modalities. Hepatobiliary excretion of Tc-99m EC usually does not usually affect the scan interpretation and quantitative renogram analysis, but reader should be cognizant of the potential pitfalls during scan interpretation. In this study, we reviewed the possible causes of this hepatobiliary clearance and importance of additional views and correlation with other imaging modalities to clarify the suspicion arises for accurate reporting.
PubMed: 38933062
DOI: 10.1055/s-0044-1779748 -
Annals of Pediatric Cardiology 2024A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of...
A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of which was not known. He was treated with decongestive measures and multiple inotropes. 2D Echocardiogram revealed severe Left ventricular dysfunction with prominent trabeculations and deep recesses in the left ventricle suggestive of Left ventricular non-compaction. He was also found to have horse-shoe kidney. Considering the presence of cardiac left ventricular non compaction, horse-shoe kidney and family history of neonatal death and pregnancy loss clinical exome sequencing was done. It detected a homozygous missense variant in exon 6 of the AGK gene suggestive of Senger's syndrome. Baby was on regular follow-up and was thriving well on diuretics, sacubitril-valsartan and weekly levosimendan infusions. At 8 months of age, cardiac transplantation was successfully done and baby has been doing well post-transplantation. LVNC in children is rare with an estimated incidence of 0.11 per 100,000, the highest incidence being during infancy. Senger's syndrome is autosomal recessive in inheritance. Senger's syndrome associated with Left ventricular non compaction has been reported only once in literature so far. Renal manifestations in the form of horse shoe kidney like in our index baby has not been reported previously with Senger's syndrome.
PubMed: 38933059
DOI: 10.4103/apc.apc_193_23 -
Viruses Jun 2024The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral...
The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral vectored vaccines is a promising approach but remains challenging due to the water removal process from the outer and inner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stress on the envelope, which often leads to the inactivation of the virus. In this study, we designed a method to freeze-dry a recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipids and 50% protein, the formulation study focused on both the protein and lipid portions of the vector. Formulations were prepared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyoprotectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and the cake stability were investigated at different final moisture content levels. High recovery of the infectious viral titer (~0.5 to 1 log loss) was found at 3-6% moisture content, with no deterioration in the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the excipients were studied. An increase from 5 to 10% in both the cryoprotectants and lyoprotectant, together with the addition of 0.5% gelatin, resulted in the improved recovery of the infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying process showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20 °C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM histidine showed satisfactory stability for six months at 2-8 °C. The development of this freeze-drying process and the optimized formulation minimize the need for a costly cold chain distribution system.
Topics: Freeze Drying; SARS-CoV-2; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; Cryoprotective Agents; Trehalose; COVID-19; Animals; Humans; Mannitol; Sucrose; Vero Cells; Chlorocebus aethiops; Sorbitol; Drug Stability; Histidine; Vesicular stomatitis Indiana virus; Vaccines, Synthetic
PubMed: 38932234
DOI: 10.3390/v16060942 -
Molecules (Basel, Switzerland) Jun 2024Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of...
Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.
Topics: Acute Lung Injury; Quercetin; Animals; Mannitol; Nanoparticles; Mice; Polymers; Cerium; Rutin; Antioxidants; Humans; Drug Synergism; Disease Models, Animal; Lipopolysaccharides
PubMed: 38930884
DOI: 10.3390/molecules29122819 -
Journal of Clinical Medicine Jun 2024Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in...
Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median ( = 0.02) and in patients who had an increase in hs-cTnT during hospitalization ( = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH ( = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events ( = 0.03). Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.
PubMed: 38930061
DOI: 10.3390/jcm13123533 -
Journal of Clinical Medicine Jun 2024This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve...
This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide ( = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone ( = 30, 51.7%). The patients treated with ACZ were younger than those without (median age 78 (range 67-86) vs. 85 (79-90) years, respectively, = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35-65) vs. 38 (26-63) mL/min, = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], = 1). No severe metabolic acidosis occurred in either group. Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ-furosemide combination in the in-hospital management of HF, especially in older, frail populations.
PubMed: 38929950
DOI: 10.3390/jcm13123421