Search Results (98)

Background/Objectives: Cardiac resynchronization therapy (CRT) is a cornerstone treatment for heart failure with reduced ejection fraction (HFrEF), yet many patients remain symptomatic despite long-term electrical optimization. Although sacubitril/valsartan (ARNI) is central to guideline-directed medical therapy (GDMT), data on its late initiation in patients with chronic CRT are scarce. This study evaluated the impact of delayed ARNI initiation on clinical status, functional capacity, and cardiac remodelling in a real-world CRT population. Methods: We performed a single-centre, retrospective observational study including 76 HFrEF patients with chronic CRT who started ARNI between 2022 and late 2024. Patients underwent standardized assessment at baseline (T0) and after 12 ± 3 months (T1), including clinical evaluation, 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), symptom-limited bicycle exercise testing, and comprehensive echocardiography. The primary endpoint was change in quality of life (QoL). Secondary endpoints included exercise capacity, echocardiographic reverse remodelling, NYHA class, loop diuretic dose, and device-detected arrhythmias. Dose–response and multidimensional response patterns were explored. Results: KCCQ-12 increased from 52.96 ± 16.33 to 75.55 ± 18.12 (Δ +22.59 ± 13.22, p < 0.001), with 89.5% achieving a clinically meaningful improvement. Exercise duration and peak workload improved significantly. LVEF increased from 35.08 ± 6.96% to 43.18 ± 8.42% (Δ +8.11%, p < 0.001), with reductions in left ventricular and atrial volumes. Loop diuretic dose decreased (median −10 mg/day furosemide equivalent, p < 0.001), and 26.3% discontinued diuretics. A lower prevalence of device-detected arrhythmias was observed at follow-up, from 34.2% to 6.6% (p < 0.001). Higher ARNI doses were associated with greater likelihood of clinical, functional, and structural response. Longer CRT duration reduced the probability of structural remodelling but not symptomatic or functional benefit. Conclusions: In patients with long-standing CRT, delayed ARNI initiation was associated with improvements in QoL, exercise capacity, cardiac remodelling, congestion status, and electrical stability. These findings suggest that CRT is not a therapeutic ceiling and that late ARNI initiation remains a valuable component of comprehensive GDMT. Full article

Background: An implantable loop recorder (ILR) represents the gold standard in the diagnosis of cardiac arrhythmias in patients with neurological or cardiac symptoms. Our study aimed to determine the real-world diagnostic effectiveness of ILRs in detecting arrhythmias requiring permanent pacemaker implantation. Methods: The study enrolled and followed up for two years 62 ILR recipients from the Cardiology Clinic of the Clinical Center Kragujevac, Serbia. Results: The most common indication for pacemaker implantation was pauses in cardiac activity (83%). The use of oral anticoagulants (OR: 11.80; 95% CI: 1.76, 79.4), ACE inhibitors or AT receptor blockers (OR: 3.87; 95% CI: 1.21, 12.35), and diuretics (OR: 5.29; 95% CI: 1.55, 18.04) had a statistically significant impact on the detection of pacemaker-requiring arrhythmias by an ILR. After adjustment for other factors of influence, oral anticoagulants (OR: 7.82; 95% CI: 1.08, 56.9) and diuretics (OR: 3.68; 95% CI: 1.04, 13.00) remained significant in predicting pacemaker requirement in ILR recipients. Conclusions: An ILR represents an effective diagnostic approach in detecting cardiac arrhythmias requiring permanent pacemaker implantation, especially in patients treated with oral anticoagulants or diuretics. Full article

Background and Objectives: Renin-angiotensin system inhibitors (RASIs) are recommended to preserve residual kidney function (RKF) in patients on peritoneal dialysis (PD); however, evidence of benefit is inconsistent. This study evaluated the effect of RASI on RKF decline among patients undergoing PD. Materials and Methods: We conducted a retrospective cohort study among PD patients at a large metropolitan dialysis centre in Australia. RKF was assessed using residual Kt/V and urine volume from PD adequacy tests. Time zero was PD initiation. RASI exposure was modelled as a time-dependent variable to avoid immortal-time bias. Linear mixed-effects models were fitted for each outcome, including random intercepts and slopes for time (years since PD start) with unstructured covariance. Fixed effects included time, RASI(t), time × RASI(t), age, sex, baseline RKF, PD modality, PD infection episodes, loop diuretic use, and comorbidities. Results: Of 307 PD patients, 231 met the inclusion criteria; 111 (48.1%) received RASI. RASI users were younger than non-users [65 years (IQR 56–74) vs. 72 years (IQR 61–77); p = 0.014]. Residual Kt/V declined by 0.26 units/year; RASI exposure showed no significant effect on urine volume trajectory and a borderline slower Kt/V decline (interaction β = +0.038, p = 0.069). Hospitalisation and PD-related infection rates were similar between groups. Conclusions: RASI therapy was not associated with meaningful RKF preservation in PD patients in this cohort. While earlier studies suggested renoprotective effects of RASI while on PD, our findings align with recent evidence of mixed efficacy. Larger prospective trials are needed to clarify the role of RASI in maintaining RKF and improving long-term outcomes in PD. Full article

(1) Background: The systemic right ventricular (SRV) dysfunction and severe tricuspid regurgitation (TR) remain significant challenges in patients with congenitally corrected transposition of the great arteries (ccTGA) or following atrial switch procedures. Currently, there is no established, evidence-based medical therapy specifically designed for SRV failure, and treatment approaches are largely extrapolated from left ventricular heart failure (HF) guidelines. This therapeutic gap highlights the need for tailored pharmacologic strategies and optimized perioperative management in this unique population. The optimal timing of surgical intervention and the role of modern HF therapy are still under active investigation. (2) Methods: We present a case series of four patients (three adults and one child) with SRV dysfunction and severe TR, who underwent staged treatment consisting of optimized medical therapy followed by surgical tricuspid valve (TV) replacement. Medical therapy included positive inotropes, sacubitril/valsartan, sodium-glucose co-transporter 2 inhibitors (iSGLT2), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and loop diuretics. (3) Results: All patients demonstrated clinical and hemodynamic improvement prior to surgery, with an increase in systemic ventricular ejection fraction (SVEF > 40%) and cardiac index. TV replacement was performed with favorable early postoperative outcomes and preserved ventricular function at mid-term follow-up. No mortality or major adverse events occurred during follow-up. One case of acute cystitis was associated with dapagliflozin. In all patients, postoperative SVEF remained >40%, and no recurrence of significant TR was observed. (4) Conclusions: A stepwise approach combining modern heart failure therapy and elective TV replacement in patients with SRV dysfunction and TR is safe and effective. Preoperative optimization leads to improved ventricular function and may enhance surgical outcomes. These findings support the integration of contemporary pharmacotherapy in the management strategy for SRV failure. Full article

Liver cirrhosis is marked by sodium and water retention, portal hypertension and sharply reduced survival after decompensation. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) induce insulin-independent glycosuria and natriuresis and have proven cardio-renal benefits, prompting interest in their role as adjuncts for ascites. This review synthesizes current evidence on efficacy, safety and mechanistic plausibility of SGLT2i in cirrhosis. Observational cohorts and case series suggest that adding SGLT2i to standard diuretics increases natriuresis, lowers ascites burden and paracentesis requirements, improves weight and aminotransferases and may reduce hepatic decompensation and hepatocellular carcinoma risk. Safety remains paramount: hypotension, acute kidney injury and hepatorenal syndrome-related acute kidney injury, genitourinary infections, electrolyte disturbances and rare euglycemic ketoacidosis necessitate careful patient selection, slow titration and close monitoring, especially in decompensated disease and when combined with loop diuretics or mineralocorticoid receptor antagonists. Overall, the balance of data supports cautious optimism: SGLT2i represent a promising adjunct within protocolized care pathways for selected patients, while definitive trials powered for hepatic outcomes are still required to clarify indications, timing, dosing and long-term impact. Full article

Left-sided congestive heart failure (CHF) is a common cause of acute respiratory distress in cats, and echocardiographic assessment of left atrial (LA) size is an important test to differentiate it from respiratory diseases that cause similar clinical signs. Furosemide, a potent loop diuretic, is the first-line therapy for cardiogenic pulmonary edema, but its effect on LA size has not been systematically investigated in cats. Some dyspneic cats are referred after having received high doses of furosemide by the referring veterinarian without prior point-of-care ultrasound (POCUS). This can make the diagnosis of CHF challenging. If furosemide significantly reduces left atrial size, it could potentially lead to misdiagnosis, by erroneously categorizing these cats as not having CHF. This prospective, observational multicenter study enrolled 25 cats with acute left-sided CHF. Point-of-care ultrasound was used to assess LA to aortic ratio (LA:Ao) and maximal LA diameter (LAD) at admission and three hours after furosemide administration. Significant reductions were observed in LA:Ao (2.48 ± 0.35 to 2.17 ± 0.40; p < 0.001), LAD (21.0 ± 2.8 mm to 18.4 ± 3.2 mm; p < 0.001), and respiratory rate (64 ± 30 to 40 ± 14 breaths/min; p < 0.001). Normalization of respiratory rate occurred in 50% of cats, while normalization of maximum LAD occurred in 32%. One cat achieved normalization of LA:Ao. We found that furosemide induced rapid reduction in LA size and respiratory rate in cats with left-sided CHF. Clinicians should be aware that severe LA dilation can be absent in referred dyspneic cats that had already received furosemide. Full article

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the symptom burden in patients with chronic kidney disease (CKD). This cross-sectional analysis included patients with CKD stages 2 to 5 from the CKD-REIN cohort and with data on the baseline serum concentrations of the free fractions of indoxyl sulphate (IS), kynurenine (KYN), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA), as measured by liquid chromatography–tandem mass spectrometry. The symptom burden was also assessed with a modified (8-item) symptom subscale from the Kidney Disease Quality of Life-36 (e.g., muscle soreness, cramps, itchy skin, dry skin, dizziness, appetite, numbness, and nausea). We used beta regressions to model the association between the furosemide dose and the symptom burden and used structural equation models to quantify the mediating effect of PBUT on this association. Among the 2053 included patients (males: 66%, median age: 68; mean estimated glomerular filtration rate: 35 mL/min/1.73 m²), those prescribed high-dose furosemide (>120 mg/day) had higher symptom burden than those not prescribed furosemide (i.e., a 5.67-point lower symptom score, 95%CI 1.41–9.93). The sum of PBUTs explained 3.78% (95%CI 0.10–18.01%) of this association. Similar results were observed for IS, KYN, and IAA, considered separately, but not for PCS, whose estimated mediation effect was nearly null. Although high-dose furosemide was associated with a greater symptom burden in patients with CKD, mediation by PBUT accumulation appeared to be minimal. Full article

Furosemide (FUR) is a loop diuretic widely used in pediatric care. However, no standardized oral liquid formulation exists due to degradation concerns, particularly the formation of furosemide-related compound B (FUR-B). This study aimed to develop and validate the HPLC method for the simultaneous quantification of FUR, FUR-B, methylparaben (MP), and propylparaben (PP) in pediatric extemporaneous oral solutions. Chromatographic separation was achieved using a Symmetry^® C18 column (4.6 × 250 mm, 5 µm) with a mobile phase of 0.1% acetic acid in water and acetonitrile (60:40, v/v) at 1.0 mL/min of flow with injection volume at 10 µL. Detection at 272 nm provided optimal sensitivity, especially for low concentrations of FUR-B. Forced degradation confirmed baseline separation of FUR from its degradation products. The condition showed high linearity (R² > 0.995), accuracy (recoveries 98.2–101.0%), and precision (RSD ≤ 2%). Robustness and ruggedness tests under varied conditions, analysts, and intra-day yielded consistent performance. Application to extemporaneous formulations showed that refrigeration (2–8 °C) retained initial composition, while elevated temperatures (30 °C and 40 °C) promoted FUR degradation, with FUR-B increasing to 6.84% after 90 days and greater MP and PP degradation. This validated method offers a reliable analytical tool for monitoring chemical changes and supporting quality control of pediatric FUR extemporaneous formulations. Full article

(1) Chronic heart failure (CHF) is a typical component of the polymorbid profile of an elderly patient. The aim of this systematic review was to search for data from pharmacokinetic (PK) studies of any drugs in patients with CHF to systematize information on changes in PK parameters depending on the physicochemical properties (PCPs) of the drug and route of its administration. (2) A systematic review of PK studies in patients with CHF was performed using Elibrary.ru, United States National Library of Medicine (PubMed), China National Knowledge Infrastructure (CNKI), and Directory of Open Access Journals (DOAJ). The final number of included articles was 106. A descriptive and correlation analysis of PK data and PCPs of drugs included in the study was carried out. Inclusion criteria: PK study, available PK parameters, demographic data, and diagnosed CHF. Risk of bias was assessed using ROBINS-I. (3) Evaluation of correlations between PCPs of drugs and their PK revealed a link between (i) plasma protein binding (PPB) and volume of distribution for lipophilic drugs; (ii) PCPs, half-life, and clearance for drugs with high PPB; and (iii) PPB and clearance for hydrophilic and amphiphilic drugs. (4) Hypoalbuminemia associated with CHF may lead to an increased volume of distribution of lipophilic drugs; lipophilic drugs used in CHF patients may be associated with prolongation of the half-life period and reduction in clearance; highly protein-bound drugs may manifest with reduced clearance. PK characteristics identified in this review should guide modifications to dosing regimens in CHF patients receiving medications from different groups. Full article

Introduction: The increasingly active role of nurses in the management of heart failure (HF) has become important in HF units (HCUs). This study aims to determine the effect of opening a specialised HF nursing (NSHF) consultation in a tertiary hospital on drug titration, and its subsequent impact on cardiac remodelling and prognosis. Methods: A retrospective cohort study was conducted on patients with HF with reduced ejection fraction (HFrEF) who were treated between 2017 and 2020. Patients who were followed by the NSHF were compared with those who underwent conventional clinical follow-up (non-NSHF), focusing on drug optimisation, echocardiographic parameters, biomarkers, and clinical outcomes in terms of mortality and hospital readmissions for HF. Results: A total of 411 patients were analysed, 85 of whom (20.7%) were treated with NSHF. There were hardly any differences in baseline characteristics. At the end of follow-up, the NSHF group had a higher prescription rate of angiotensin receptor–neprilysin inhibitor (+31.7% vs. +23.3%; p < 0.001), beta-blockers (+2.4% vs. −5.8%; p < 0.001), and sodium glucose co-transporter type 2 inhibitors (+24.7% vs. +17.8%; p < 0.001). There was also a higher rate of loop diuretic withdrawal (−16.7% vs. −6.7%; p < 0.001). However, no improvement in reverse remodelling or neurohormonal response was observed. Patients treated with NSHF had a lower probability of dying from HF (88.6% vs. 63.3%; p = 0.006), but this did not reduce hospital admissions for HF. Conclusions: Patients with HFrEF who are cared for through NSHF are more likely to be prescribed drugs that modify the prognosis of the disease. This has an impact on their mortality. Full article

Background/Objectives: Overcoming resistance to diuretics is extremely important in decompensated chronic heart failure (HF). The objective of this study was to assess the efficacy and safety of oral acetazolamide, in addition to standard therapy, in HF patients admitted to the hospital with decompensation requiring intravenous loop diuretic therapy. Methods: In this open-label, prospective, multicenter, randomized trial, we included 416 patients hospitalized with decompensated HF. The patients were randomized into two groups: (1) standard therapy, and (2) standard therapy + acetazolamide orally 250 mg 3 times a day in the first 3 days of hospitalization. At randomization, oral thiazide/thiazide-like and loop diuretics were stopped, and intravenous furosemide was initiated. Results: Successful decongestion within 72 h of randomization was observed in 82 patients (39.6%) in the acetazolamide group and in 83 patients (39.7%) in the standard therapy group (p = 0.983). There was a significant difference in the increase in diuresis in the first 72 h (p = 0.028) and in natriuresis on the 2nd day (p = 0.04). There were no differences between the groups in duration of stay in the intensive care unit, duration of index hospitalization, 6 min walk test distance, and clinical assessment scale scores. Death from any cause occurred in three (1.4%) patients in the acetazolamide group, and in the same number of patients in the standard therapy group (p = 0.996). Death from cardiovascular cause and due to decompensated HF also did not differ between the groups during follow-up. Conclusions: The addition of acetazolamide to standard therapy in decompensated chronic HF resulted in a higher cumulative urine output during the first 72 h and natriuresis on the 2nd day after randomization. Full article

Background: Adherence to current clinical guidelines is crucial for ensuring optimal therapy in patients with heart failure (HF). This study aims to explore how cardiologists, as specialists in heart failure, approach the clinical scenarios encountered in the management of HF patients, in line with the recommended guidelines. A heart failure-focused meeting was organized, during which participating cardiologists engaged actively. During HF meetings in which cardiologists participated, 108 questionnaires were distributed electronically. In total, 57 men and 51 women expressed their opinions regarding the Delphi analysis. Results: A strong consensus on the benefits of beta-blockers in improving prognoses for, and reducing mortality in, patients with HF and reduced systolic function emerged. The majority of cardiologists continue to prefer intravenous therapy with continuous loop-diuretic administration in combination with thiazide diuretics. The use of metolazone elicits fewer preferences, probably due to concerns about side effects. Certainly, SGLT2i is useful in reducing hospitalizations and reducing congestion; however, there is no full consensus on whether MRAi should be discontinued in favor of SGLT2i alone. The majority of participants would discontinue MRAs in the presence of hyperkalemia and worsening renal function, maintaining sacubitril/valsartan, and indicating a priority for renal safety. There was near-unanimous agreement on the early initiation of sacubitril/valsartan after the stabilization of patients hospitalized for heart failure. Conclusions: A significant majority (97%) of cardiologists expressed a preference for utilizing all of the guideline-recommended drug classes in the management of heart failure, even if this meant not always reaching the maximum tolerated dose for each medication. This approach underscores the importance of comprehensive therapy, targeting multiple pathophysiological mechanisms in heart failure. Cardiologists emphasized that while achieving optimal dosing is ideal, flexibility in treatment regimens is often necessary to accommodate individual patient characteristics, tolerance, and clinical status. The findings highlight the need for personalized treatment strategies that align with current guidelines, while also recognizing the challenges and variability in patient responses to therapy. Full article

Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid–base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia—often iatrogenic—may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride’s role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome. Full article

Background/Objectives: Loop diuretics are among the most commonly used drugs in patients with heart failure with reduced ejection fraction (HFrEF). Higher doses of these diuretics are associated with poorer clinical status and may contribute to malnutrition. The study aims to assess the relationship between the use of high-dose loop diuretics and nutritional status in patients with HFrEF. Methods: The study included 353 hospitalized patients with HFrEF. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), the Geriatric Nutritional Index (GNRI), and the CONtrolling NUTritional status (CONUT). Patients were divided into three groups according to the daily dose of loop diuretics (defined as furosemide equivalent = 1 × furosemide dose and 2 × torsemide dose): low dose (LD), 40 mg/day or no treatment; medium dose (MD), 41–160 mg/day; or high dose (HD), >160 mg/day. Results: Of the evaluated patients, the mean MNA score was 23.31 ± 2.93 points, and 49.8% were at risk of malnutrition or malnourished. According to the MNA, patients in HD and MD groups had worse nutritional status than the LD group, similarly according to the GNRI. For CONUT, the differences were significant between all groups: nutritional status was the worst in the HD group, intermediate in the MD group, and the best in the LD group. Conclusions: The intake of loop diuretics, especially in high doses, correlates with an elevated risk of malnutrition in patients with HFrEF independently of sex, age, NYHA class, and left ventricular ejection fraction. Full article

Loop diuretics like furosemide are commonly used in heart failure (HF) treatment, but their effects on disease progression are still unclear. Furosemide treatment accelerates HF deterioration in a swine model, but the mechanism of acceleration is poorly understood. We hypothesized that furosemide activates inflammatory signaling in the failing left ventricular (LV) myocardium, leading to adverse remodeling of the extracellular matrix (ECM). A total of 14 Yorkshire pigs underwent permanent transvenous pacemaker implantation and were paced at 200 beats per minute; 9 non-instrumented pigs provided controls. Seven paced animals received normal saline, and seven received furosemide at a dose of 1 mg/kg intramuscularly. Weekly echocardiograms were performed. Furosemide-treated animals reached the HF endpoint a mean of 3.2 days sooner than saline-treated controls (mean 28.9 ± 3.8 SEM for furosemide and 32.1 ± 2.5 SEM for saline). The inflammatory signaling protein transforming growth factor-beta (TGF-β) and its downstream proteins were significantly (p ≤ 0.05) elevated in the LV after furosemide treatment. The regulatory factors in cell proliferation, mitogen-activated protein kinase signaling pathway proteins, and matrix metalloproteinases were elevated in the furosemide-treated animals (p ≤ 0.05). Our data showed that furosemide treatment increased ECM remodeling and myocardial fibrosis, reflecting increased TGF-β signaling factors, supporting prior results showing worsened HF. Full article