Treatment Of Congestive Heart Failure Research Articles

Nitroxyl donating and visualization with a coumarin-based fluorescence probe

Nitroxyl (HNO), the single-electron reduction product of nitric oxide (NO), has attracted great interest in the treatment of congestive heart failure in clinical trials. In this paper, we describe the first coumarin-based compound N-hydroxy-2-oxo-2H-chromene-6-sulfonamide (CD1) as a dualfunctional HNO donor, which can release both an HNO signaling molecule and a fluorescent reporter. Under physiological conditions (pH 7.4 and 37 °C), the CD1 HNO donor can readily decompose with a half-life of ∼90 min. The corresponding stoichiometry HNO from the CD1 donor was confirmed using both Vitamin B12 and phosphine compound traps. In addition to HNO releasing, specifically, the degradation product 2-oxo-2H-chromene-6-sulfinate (CS1) was generated as a fluorescent marker during the decomposition. Therefore, the HNO amount released in situ can be accurately monitored through fluorescence generation. As compared to the CD1 donor, the fluorescence intensity increased by about 4.9-fold. The concentration limit of detection of HNO releasing was determined to be ∼0.13 μM according to the fluorescence generation of CS1 at physiological conditions. Moreover, the bioimaging of the CD1 donor was demonstrated in the cell culture of HeLa cells, where the intracellular fluorescence signals were observed, inferring the site of HNO release. Finally, we anticipate that this novel coumarin-based CD1 donor opens a new platform for exploring the biology of HNO.

Cost-Effectiveness of Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation in the Australian Health Care System

Heart transplantation is an effective treatment for end-stage congestive heart failure, however, achieving the right balance of immunosuppression to maintain graft function while minimising adverse effects is challenging. Serial endomyocardial biopsies (EMBs) are currently the standard for rejection surveillance, despite being invasive. Replacing EMB-based surveillance with cardiac magnetic resonance (CMR)-based surveillance for acute cardiac allograft rejection has shown feasibility. This study aimed to assess the cost-effectiveness of CMR-based surveillance in the first year after heart transplantation. A prospective clinical trial was conducted with 40 orthotopic heart transplant (OHT) recipients. Participants were randomly allocated into two surveillance groups: EMB-based, and CMR-based. The trial included economic evaluations, comparing the frequency and cost of surveillance modalities in relation to quality-adjusted life years (QALYs) within the first year post-transplantation. Sensitivity analysis encompassed modelled data from observed EMB and CMR arms, integrating two hypothetical models of expedited CMR-based surveillance. In the CMR cohort, 238 CMR scans and 15 EMBs were conducted, versus (vs) 235 EMBs in the EMB group. CMR surveillance yielded comparable rejection rates (CMR 74 vs EMB 94 events, p=0.10) and did not increase hospitalisation risk (CMR 32 vs EMB 46 events, p=0.031). It significantly reduced the necessity for invasive EMBs by 94%, lowered costs by an average of AUD$32,878.61, and enhanced cumulative QALY by 0.588 compared with EMB. Sensitivity analysis showed that increased surveillance with expedited CMR Models 1 and 2 were more cost-effective than EMB (all p<0.01), with CMR Model 1 achieving the greatest cost savings (AUD$34,091.12±AUD$23,271.86 less) and utility increase (+0.62±1.49 QALYs, p=0.011), signifying an optimal cost-utility ratio. Model 2 showed comparable utility to the base CMR model (p=0.900) while offering the benefit of heightened surveillance frequency during periods of elevated rejection risk. CMR-based rejection surveillance in orthotopic heart transplant recipients provides a cost-effective alternative to EMB-based surveillance. Furthermore, it reduces the need for invasive procedures, without increased risk of rejection or hospitalisation for patients, and can be incorporated economically for expedited surveillance. These findings have important implications for improving patient care and optimising resource allocation in post-transplant management.

Pharmacological Mechanisms of Periplocae Cortex Against Congestive Heart Failure Based on Network Pharmacology and Experimental Evaluation

Background Periplocae cortex is a well-known Traditional Chinese Medicine with abundant effects, including the treatment of chronic congestive heart failure (CHF). However, the principal components and mechanisms have not been fully elucidated. This study aims to analyze the active ingredients and potential mechanisms of the periplocae cortex in CHF treatment. Methods TCMSP, GeneCards, and Comparative Toxicogenomics databases were used to mine the active ingredients and potential targets of the periplocae cortex. Cytoscape 3.9.1 software was employed to construct the “periplocae cortex-active ingredients-potential targets” and protein–protein interaction network. The DAVID 6.8 database was used for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the predicted targets. The protective effects of β-sitosterol (BSS) were detected in doxorubicin (Dox)-induced H9c2 cells using MTT assay, while the regulatory pathways of BSS were examined using various assays, including real-time quantitative PCR and Western blot. The cardiac troponin I (cTn-I) concentration was also measured. Results A total of 13 active ingredients were identified, and 33 targets of CHF were predicted. Network analysis highlighted BSS as the key active ingredient, interacting with 29 targets. GO and KEGG analyses indicated significant involvement of these targets in calcium and apoptosis signaling pathways. Experimental findings demonstrated that BSS enhanced cell viability, reduced intracellular calcium ion concentration, and inhibited caspase 3 activity in Dox-induced H9c2 cells. BSS significantly altered the expression of CHRM1, CASP3, and CASP9 genes ( P &lt; .05), and increased CHRM2 expression. Additionally, BSS significantly increased cTn-I concentration. Notably, suppression of calcium and apoptosis signaling pathways partially mitigated BSS's effects on cell viability and cTn-I concentration. Conclusion Through network pharmacology and experimental verification, establishes BSS as a key active ingredient in the periplocae cortex for CHF treatment. BSS appears to modulate calcium and apoptosis signaling pathways, thereby exerting therapeutic effects in the treatment of CHF.

A brief review on medicinal Digitalis L. species grown in the ʺAlexandru Ciubotaruʺ National Botanical Garden (Institute)

The paper presents a brief review on the medicinal importance and possibilities of capitalization of Digitalis L. taxa (D. ciliata Trautv., D. ferruginea L., D. grandifl ora Mill., D. laevigata Waldst. ex Kit., D. lanata Ehrh., D. lutea L., D. lutea subsp. australis (Ten.) Arcang., D. purpurea L., D. purpurea var. albifl ora Lej.) intro duced in the Natio nal Botanical Garden (Institute) “Al. Ciubotaru”. The main morphological characteristics of the plants are described, the bioactive components and medicinal properties are summarized. The notable presence of cardioactive glycosides in the species D. lanata and D. purpurea make them the most important drugs in the treatment of congestive heart failure. The review also indicate the therapeutic potential of other Digitalis L. species which point the way to conduct further studies in order to establish and explore their medicinal value.

Comparative study between homemade and commercial hawthorn (Crataegus spp.) extracts regarding their phenolic profile and antioxidant activity

Crataegus species (hawthorn) have been commonly used in traditional medicine, especially for the treatment of congestive heart failure. Many studies confirmed that they are rich in polyphenols, thus exhibiting strong antioxidant activity, which contribute to the beneficial effects of hawthorn on the cardiovascular system. In the market, there are many herbal medicinal products based on hawthorn, which consumption as adjuvant therapy in heart-related issues is supported by European Medicines Agency. Since there is a global trend of making homemade herbal preparations, this study aimed to compare whether there is a difference in polyphenol profile and antioxidant potential between homemade and commercial ethanol extracts of hawthorn. Polyphenol profile was evaluated by determination of total phenolic and flavonoid contents, and by quantitative analysis of selected polyphenols by LC-MS/MS. Antioxidant potential was examined by DPPH, FRAP, and lipid peroxidation inhibition assays. The results of this study suggest that homemade ethanol extracts of hawthorn flowers, leaves and fruits are just as good source of polyphenols and antioxidants as commercial ones, and their utilization should be supported. Furthermore, hawthorn extracts made of leaves and flowers are better source of bioactive polyphenols and have higher antioxidant activity compared with the same of fruits, regardless of the method of preparation.

Beyond Glycemic Control: Mechanistic Insights Into SGLT-2 Inhibitors in Heart Failure Management.

Heart failure is a common and clinically significant cardiac condition that causes significant morbidity and mortality in the United States. Diabetes and hypertension are 2 of the most common comorbidities associated with heart failure. Other risk factors for heart failure include smoking, obesity, and intrinsic cardiac diseases such as myocardial infarction and valvular pathologies. All of these conditions, to some extent, cause remodeling within the cardiomyocyte, which eventually leads to the development of congestive heart failure. Over the years, using diuretics and medications that inhibit the Renin-Angiotensin-Aldosterone System has been the traditional treatment for congestive heart failure. But in recent years studies in the diabetic population revealed that sodium-glucose cotransporter-2 inhibitors had a negative impact on the remodeling of cardiomyocytes. In this review, we discuss the numerous molecular mechanisms by which these recently developed medicines inhibit remodeling in cardiomyocytes, independent of their intended effect of decreasing blood glucose levels. Furthermore, it emphasizes the use of these drugs in diabetic as well as non-diabetic patients as a promising adjunct to ongoing heart failure treatment.

Carbohydrate antigen 125 in congestive heart failure: ready for clinical application?

Congestion is the permanent mechanism driving disease progression in patients with acute heart failure (AHF) and also is an important treatment target. However, distinguishing between the two different phenotypes (intravascular congestion and tissue congestion) for personalized treatment remains challenging. Historically, carbohydrate antigen 125 (CA125) has been a frequently used biomarker for the screening, diagnosis, and prognosis of ovarian cancer. Interestingly, CA125 is highly sensitive to tissue congestion and shows potential for clinical monitoring and optimal treatment of congestive heart failure (HF). Furthermore, in terms of right heart function parameters, CA125 levels are more advantageous than other biomarkers of HF. CA125 is expected to become a new biological alternative marker for congestive HF and thereby is expected be widely used in clinical practice.

Epidemiological study of vaccination against SARS-CoV-2 and its impact on COVID-19 progression in a cohort of patients in gran Canaria

ObjectivesWe analyzed the impact of age, sex, vaccination against COVID-19, immunosuppressive treatment, and comorbidities on patients' risk of requiring hospital admission or of death. MethodsPopulation-based observational retrospective study conducted on a cohort of 19,850 patients aged 12 years or more, who were diagnosed with COVID-19 between June 1st and December 31st, 2021, in the island of Gran Canaria. ResultsHypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities; 147 patients died (0.7%). The combination of advanced age, male sex, cancer, coronary heart disease, immunosuppressive treatment, hospital admission, admission to the intensive care unit, mechanical ventilation and lack of complete COVID-19 vaccination or booster dose was strongly predictive of mortality (p < 0.05); 831 patients required hospital admission and it was more frequent in men, older age groups, and patients with cancer, diabetes, arterial hypertension, chronic obstructive pulmonary disease, congestive heart failure or immunosuppressive treatment. The COVID-19 vaccine booster dose was associated with a lower risk of death ([OR] 0.11, 95% CI 0.06–0.21, p < 0.05) or hospital admission ([OR] 0.36, 95% CI 0.29–0.46, p < 0.05). ConclusionsCancer, coronary heart disease, and immunosuppressive treatment were associated with increased COVID-19 mortality. More complete vaccination was associated with lower risk of hospital admission or death. Three doses of the SARS-CoV-2 vaccine were highly associated with the prevention of death and hospital admission in all age groups. These findings suggest that COVID-19 vaccination can help bring the pandemic under control.

The Enigma of Heart-kidney Transplantation.

The Enigma of Heart-kidney Transplantation.

N-acetyldopamine oligomers from Periplaneta americana with anti-inflammatory and vasorelaxant effects and their spatial distribution visualized by mass spectrometry imaging

Ethnopharmacological relevancePeriplaneta americana is a medicinal insect that has been applied to promote blood circulation and remove blood stasis based on traditional Chinese medicine (TCM) for a long time. Its modern preparation, Xinmailong injection, was adopted for the treatment of congestive heart failure (CHF). The bioactive constituents of P. americana and their correlation with its traditional uses need further investigation. Aim of the studyThis study aimed to elucidate the N-acetyldopamine (NADA) oligomers from P. american, determine their spatial distribution, and investigate their anti-inflammatory and vasorelaxant effects to provide scientific evidence supporting the clinical use of this medicinal insect. Material and methodsNADA oligomers were isolated from the CH2Cl2: CH3OH (2:1) extract of P. americana, through sequential chromatographic methods including silica gel, Sephadex LH-20, preparative HPLC, and chiral-phase separation. Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopic analysis, chiral resolution, and calculated electronic circular dichroism analysis. With the aid of atmospheric pressure scanning matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI), the isolated compounds in a spatial profile within P. americana were identified. NO production was measured to assess anti-inflammatory activity. Vasorelaxant activity assessments were performed on the norepinephrine-precontracted 3rd-order mesenteric arteries. ResultsSeven new NADA trimers, peridopamines A−G (1−7), two new NADA dimers, peridopamines H and I (8 and 9), and six known NADA derivatives (10−15), were obtained from P. americana. The trimers and dimers were detected and showed similar pattern of distribution with accumulation in peripheral and rigid parts of P. americana, based on quasimolecular ion AP-SMALDI MS images of sections from the whole body and dissected areas of the insect. Furthermore, the anti-inflammatory and vasorelaxant effects of isolated compounds were investigated. Compounds 8 and 9 presented significant and moderate anti-inflammatory potentials, respectively. Compounds 8, 10, 12 and 15 possess significant vasorelaxant potentials at concentrations correlated with EC50 values of 6.7–23.7 μM. ConclusionFifteen NADA oligomers were isolated from P. americana. The distribution of these compounds was visualized by AP-SMALDI imaging experiments and NADA oligomers were mainly observed in peripheral parts. Bioassays showed that the tested compounds had anti-inflammatory and vasorelaxant activities, which indicated that NADA oligomers are active ingredients of this insect-based TCM and have potential for the treatment of cardiovascular disease.

The effect of taurine supplementation on the renin–angiotensin–aldosterone system of dogs with congestive heart failure

The role of taurine in the treatment of congestive heart failure (CHF) in dogs without systemic deficiency is unexplored. Taurine might have beneficial cardiac effects aside from deficit replacement. We hypothesized that oral taurine supplementation administered to dogs with naturally-occurring CHF would suppress the renin-angiotensin aldosterone system (RAAS). Oral taurine was administered to 14 dogs with stable CHF. Serum biochemical variables, blood taurine concentrations, and comprehensive analysis of RAAS variables were compared before and 2 weeks after taurine supplementation added to background furosemide and pimobendan therapy for CHF. Whole blood taurine concentrations increased after supplementation (median 408 nMol/mL, range 248–608 before and median 493 nMol/mL, range 396–690 after; P = .006). Aldosterone to angiotensin II ratio (AA2) was significantly decreased after taurine supplementation (median 1.00, range 0.03–7.05 before and median 0.65, range 0.01–3.63 after; P = .009), but no other RAAS components significantly differed between timepoints. A subset of dogs showed marked decreases in RAAS metabolites after supplementation and these dogs were more likely to have been recently hospitalized for CHF treatment than dogs that did not show marked decreases in classical RAAS metabolites. Overall, taurine only lowered AA2 in this group of dogs, however, response heterogeneity was noted, with some dogs showing RAAS suppression.

Dobutamine-induced alternations in cerebral blood flow of healthy adults: a 3D pseudocontinuous arterial spin labeling study

BackgroundIt is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics.MethodsForty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes.ResultsHR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60–21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45–0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05–116.53, P = 0.046) were significantly associated with frontal lobe CBF changes.ConclusionsDobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.

Epidemiological study of vaccination against SARS-CoV-2 and its impact on COVID-19 progression in a cohort of patients in gran Canaria

ObjectivesWe analyzed the impact of age, sex, vaccination against COVID-19, immunosuppressive treatment, and comorbidities on patients' risk of requiring hospital admission or of death. MethodsPopulation-based observational retrospective study conducted on a cohort of 19,850 patients aged 12 years or more, who were diagnosed with COVID-19 between June 1st and December 31st, 2021, in the island of Gran Canaria. ResultsHypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities; 147 patients died (0.7%). The combination of advanced age, male sex, cancer, coronary heart disease, immunosuppressive treatment, hospital admission, admission to the intensive care unit, mechanical ventilation and lack of complete COVID-19 vaccination or booster dose was strongly predictive of mortality (p < 0.05); 831 patients required hospital admission and it was more frequent in men, older age groups, and patients with cancer, diabetes, arterial hypertension, chronic obstructive pulmonary disease, congestive heart failure or immunosuppressive treatment. The COVID-19 vaccine booster dose was associated with a lower risk of death ([OR] 0.11, 95% CI 0.06–0.21, p < 0.05) or hospital admission ([OR] 0.36, 95% CI 0.29–0.46, p < 0.05). ConclusionsCancer, coronary heart disease, and immunosuppressive treatment were associated with increased COVID-19 mortality. More complete vaccination was associated with lower risk of hospital admission or death. Three doses of the SARS-CoV-2 vaccine were highly associated with the prevention of death and hospital admission in all age groups. These findings suggest that COVID-19 vaccination can help bring the pandemic under control.

Formulation, optimization and in vitro evaluation of polymer-coated liposomes encapsulating nebivolol hydrochloride

Hypertension, also known as high blood pressure, is a serious medical condition that affects billions of people worldwide. Nebivolol hydrochloride, a β1–adrenergic blocking agent, is used by the oral route in the treatment of hypertension and congestive heart failure. However, its lipophilic nature and poor aqueous solubility restricts its oral bioavailability. To overcome limitations related with conventional oral formulations of the drug, uncoated and polymer–coated liposomes were developed and evaluated. Liposomes loaded with nebivolol hydrochloride were prepared by thin–film hydration method and characterized. The influence of chitosan or pluronic (F127) coating on the liposome properties was evaluated in terms of physicochemical characteristics, stability in simulated gastrointestinal fluids, mucin interaction, in vitro drug release and cytotoxicity studies. It was observed that coating the liposomes with either chitosan or pluronic affected the size, surface charge and encapsulation efficiency of the formulations. The surface morphology studies confirmed the vesicular shape of liposomes. The results obtained indicated that both polymer–coated liposome formulations maintained their stability in simulated gastrointestinal fluids and showed significant in vitro interaction with mucin. Polymer–coated liposome formulations showed much better cumulative release of the drug than uncoated liposomes. No aggregation was observed at the end of four–week storage period and low toxicity in Caco–2 cells was measured. The results demonstrated that polymer coating of liposomes could enhance the in vitro release of nebivolol hydrochloride and interaction with mucin following oral administration and might be attractive alternative nanocarriers to traditional oral formulations.

'Conventional' haemodynamics even in the quadricuspid aortic valve: clinical recognition using multimodality imaging.

A 76-year-old male with congestive heart failure, accompanied by dyspnoea and irregular rhythm, was transferred to our hospital for treatment of congestive heart failure (NYHAIII/IV). Atrial fibrillation was confirmed by electrocardiography, and transoesophageal echocardiography (TEE) for electrical cardioversion was performed due to poor response to medical therapy. Two- and three-dimensional TEE revealed a quadricuspid aortic valve (QAV) with central leaflet malcoaptation and restriction of valve leaflet opening (Panels A and B; Supplementary data online, Videos S1 and S2). After electrical cardioversion, transthoracic echocardiography showed severe aortic stenosis with a 4.9 m/s peak aortic valve flow velocity, mean pressure gradient of 56 mm Hg (Panel C), and severe aortic regurgitation; the regurgitant volume was 61 mL/beat, and vena contracta width was 6.1 mm (Panel D; Supplementary data online, Video S3). Multi-detector row computed tomography confirmed the QAV and showed no dilatation of the ascending aorta (diameter, 34 mm) (Panels E and F). Four-dimensional flow cardiovascular magnetic resonance was confirmed that blood flow in the ascending aorta had a normal flow pattern; peak systolic wall shear stress values were not high, and symmetrical helical flow was observed (Panels G and H; Supplementary data online, Videos S4 and S5). Based on these results, TAVI was also considered, but we determined that simultaneous intervention for atrial fibrillation was necessary. Therefore, surgical aortic valve replacement (bioprosthetic valve), pulmonary vein isolation, and left atrial appendage closure were performed (Panels I and J). This case underlines the importance of multimodality approach to the diagnosis and treatment strategy of QAV.

Rural-urban trends in health care utilization, treatment, and mortality among US veterans with congestive heart failure: A retrospective cohort study.

To compare longitudinal rates of health care utilization, evidence-based treatment, and mortality between rural and urban-dwelling patients with congestive heart failure (CHF). We used electronic medical record data from the Veterans Health Administration (VHA) to identify adult patients with CHF from 2012 through 2017. We stratified our cohort using left ventricular ejection fraction percentage at diagnosis (<40% = reduced ejection fraction [HFrEF]; 40%-50% = midrange ejection fraction [HFmrEF]; >50% = preserved ejection fraction [HFpEF]). Within each ejection fraction cohort, we stratified patients into rural or urban groups. We used Poisson regression to estimate annual rates of health care utilization and CHF treatment. We used Fine and Gray regression to estimate annual hazards of CHF and non-CHF mortality. One-third of patients with HFrEF (N = 37,928/109,110), HFmrEF (N = 24,447/68,398), and HFpEF (N = 39,298/109,283) resided in a rural area. Rural compared to urban patients used VHA facilities at similar or lower annual rates for outpatient specialty care across all ejection fraction cohorts. Rural patients used VHA facilities at similar or higher rates for primary care and telemedicine-delivered specialty care. They also had lower and declining rates of VHA inpatient and urgent care use over time. There were no meaningful rural-urban differences in treatment receipt among patients with HFrEF. On multivariable analysis, the rate of CHF and non-CHF mortality was similar between rural and urban patients in each ejection fraction cohort. Our findings suggest the VHA may have mitigated access and health outcome disparities typically observed for rural patients with CHF.

Comparison of Periprocedural and Intermediate-Term Outcomes of TAVI in Patients with Ejection Fraction ≤ 20% vs. Patients with 20% &lt; EF ≤ 40%

Treatment of congestive heart failure (CHF) with left ventricular (LV) systolic dysfunction and severe aortic stenosis (AS) is challenging, yet transcatheter aortic valve replacement (TAVR) has emerged as a suitable treatment option in such patients. We compared the periprocedural outcomes of TAVR in patients with an ejection fraction (EF) of ≤20% (VLEF group) to patients with an EF > 20% to ≤40% (LEF group). We included patients with severe AS and reduced LV ejection fraction (LVEF ≤ 40%) who underwent TAVR at four centers within Northwell Health between January 2016 and December 2020. Over 2000 consecutive patients were analyzed, of which 355 patients met the inclusion criteria. The primary composite endpoint was in-hospital mortality, moderate or greater paravalvular (PVL), stroke, conversion to open surgery, aortic valve re-intervention, and/or need for PPM. Secondary endpoints were length of stay, NYHA classification at 1 month and 1 year, mortality at 1 month and 1 year, mean valve gradient at 1 month, KCCQ score at 1 month, and ≥ moderate PVL at 1 month. There was no difference in the primary composite endpoint between the two groups (23.6% for VLEF vs. 25.3% for LEF, p = 0.29). During TAVR placement, 40% of patients in the VLEF group required ≥1 vasopressors for hypotension lasting ≥30 min vs. only 21% of patients in the LEF group (p < 0.01). Intra-aortic balloon pump (IABP) use during procedure was greater in the VLEF group (9% vs. 1%, p < 0.01)-all placed post TAVR. Emergency ECMO use was higher in the VLEF group as well (5% vs. 0%). Total length of stay was significantly different between the two groups as well (6 days vs. 3 days, p < 0.01). Both groups had a change in LVEF of ~10%. One-year outcomes were similar between the groups. All-cause mortality at 1 year was not significantly different at 1 year (13% for VLEF vs. 11% for LEF), and KCC scores were also similar (77.54 vs. 74.97). Mean aortic valve gradients were also similar (12 mmHg vs. 11 mmHg, p = 0.48). Our study suggests that patients with EF ≤ 20% can safely have TAVR with similar periprocedural outcomes compared to patients with EF > 20% to ≤40% despite higher rates of vasopressor and mechanical support.

Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method.

Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR (1H, 13C, and DEPT), and 2D-NMR (1H-1H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II.

Hyperkalemia and the Use of New Potassium Binders a Single Center Experience from Vestfold Norway (The PotBind Study).

Hyperkalemia is a common metabolic complication of chronic kidney disease (CKD) and is associated with several serious adverse events. We aimed to treat/prevent hyperkalemia using the new of potassium-binders, allowing maintained renin-angiotensin-aldosterone system inhibitors (RAASi) treatment in proteinuric CKD and/or congestive heart failure (CHF) patients. We conducted a retrospective cohort study in long-term users of potassium binders for chronic hyperkalemia. Patients aged 18 years and older, treated with potassium-binders and who met the reimbursement criteria and indication for RAASi treatment were included. Fifty-seven percent of the patients were males and mean age was 65 years. During the study period, no patients were admitted to hospital due to hyperkalemia after initiation of potassium binders. Potassium maximum values were significantly lower after treatment. Few patients reported major side effects, and discontinuation was mostly due to normokalemia. We found no significant changes in bicarbonate, serum creatinine or GFR stage after starting potassium binder treatment. All patients on RAASi treatment before initiating potassium-binders were retained on RAASi treatment. New potassium binders in clinical practice are an easy and safe treatment with few side effects and good tolerance, that significantly lowers the risk of hyperkalemia. Furthermore, and most importantly, patients can be maintained on RAASi treatment.

Development of a quaternary ammonium poly (amidoamine) dendrimer-based drug carrier for the solubility enhancement and sustained release of furosemide.

Furosemide (FRSD) is a loop diuretic that has been categorized as a class IV drug according to the Biopharmaceutics Classification System (BCS). It is used in the treatment of congestive heart failure and edema. Owing to low solubility and permeability, its oral bioavailability is very poor. In this study, two types of poly (amidoamine) dendrimer-based drug carriers (generation G2 and G3) were synthesized to increase the bioavailability of FRSD through solubility enhancement and sustained release. The developed dendrimers enhanced the solubility of FRSD 58- and 109-fold, respectively, compared with pure FRSD. In vitro studies demonstrated that the maximum time taken to release 95% of the drug from G2 and G3 was 420-510min, respectively, whereas for pure FRSD the maximum time was only 90min. Such a delayed release is strong evidence for sustained drug release. Cytotoxicity studies using Vero and HBL 100 cell lines through an MTT assay revealed increased cell viability, indicating reduced cytotoxicity and improved bioavailability. Therefore, the present dendrimer-based drug carriers are proven to be prominent, benign, biocompatible, and efficient for poorly soluble drugs, such as FRSD. Therefore, they could be convenient choices for real-time applications of drug delivery.