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Background While loop diuretics remain a cornerstone of heart failure (HF) management, evidence directly comparing the clinical outcomes of torasemide and furosemide is still not clear. Objectives We aimed to assess the comparison of mortality between furosemide and torasemide in patients with HF. Methods This single‐center, retrospective, and observational cohort study included 627 patients with HF who were regularly prescribed furosemide or torasemide and were admitted to the emergency department or cardiology outpatient clinic between January 1, 2022, and June 30, 2023. Patients were divided into the two groups as follows: the furosemide group and the torasemide group. The primary outcome was defined as 1‐year all‐cause mortality. The primary outcome was assessed by Kaplan−Meier analyses in the whole study population and the 1:1 propensity score−matched cohort. Results Of 627 eligible patients with HF, 497 were treated with furosemide, while 130 received torasemide. After propensity score matching analysis, 82 patients with HF in the furosemide group were compared with 82 patients with HF in the torasemide group. In the furosemide group, 1‐year all‐cause mortality was observed in 15 (18.3%) patients with HF, compared to 13 (15.9%) patients with HF in the torasemide group (p: 0.678). Kaplan−Meier analysis showed that cumulative survival rates were comparable between the HF patients treated with furosemide and those treated with torasemide (log‐rank p: 0.661). Conclusions In patients with HF, treatment with torasemide was associated with similar 1‐year all‐cause mortality compared to furosemide, underscoring the absence of a detectable prognostic difference between the two loop diuretic strategies.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, β blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and β blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations. •By understanding and addressing differences in guideline-directed medical treatment responses between sex, healthcare providers can optimize patient outcomes and reduce the burden of heart failure (HF) on patients and healthcare systems.•The most effective combinations of HF drugs in reducing all-cause mortality were those with sodium/glucose cotransporter-2 inhibitors in both male and female patients.•The use of digoxin showed different responses in male and female hospitalized patients with HF when added into first-line guideline-directed medical therapy.•Compared with monotherapy, each combination, including recommended drugs by the current guidelines, did not show similar efficacy on all-cause mortality in both sexes with HF.

Background In the contemporary management of heart failure with reduced ejection fraction (HFrEF), the recommended quadruple guideline-directed medical therapy (GDMT) consists of angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This study explored the impact of adding implantable cardioverter-defibrillator (ICD) therapy to this comprehensive regimen in HFrEF patients. Methods Utilizing deidentified data from the National Electronic Database of the Turkish Ministry of Health, we conducted a nationwide retrospective cohort study on 5450 HFrEF patients receiving quadruple GDMT, including ARNI. Among them, 709 patients underwent additional ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Propensity score matching ensured balanced baseline characteristics between groups. Primary endpoint was determined as all-cause mortality. Results In the matched cohort, all-cause mortality occurred in 108 out of 619 patients (17.4%) in the GDMT group and 101 out of 619 patients (16.3%) in the ICD group, with a hazard ratio (HR) of 0.74 and a 95% confidence interval (CI) ranging from 0.57 to 0.98. The median follow-up time was 1365 days in the matched cohort, 1283 days in the GDMT group. Subgroup analyses consistently demonstrated benefits, particularly among individuals aged 61 years and older (HR: 0.60, 95% CI: 0.42–0.87, p  = 0.006), those with sinus rhythm (HR: 0.55, 95% CI: 0.34–0.89, p  = 0.013), individuals not using amiodarone (HR: 0.61, 95% CI: 0.42–0.89, p  = 0.011), and those with an estimated glomerular filtration rate lower than 61.9 (HR: 0.66, 95% CI: 0.48–0.91, p  = 0.011). Conclusions This study may offer a glimmer of hope that even after achieving the best current optimal medical therapy, the addition of device therapy could still yield positive outcomes in the management of patients with HFrEF. Graphical Abstract

Purpose Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia–reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. Methods Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n  = 8), sedentary-dexamethasone treated (D, n  = 8), and exercise training-dexamethasone treated (DE, n  = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg −1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min −1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. Results The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats ( p  < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase ( p  > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression ( p  < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation ( p  < 0.05; C vs. D) ( p  < 0.001; DE vs. D). Conclusion Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.

Giriş ve Amaç:Akut miyokard infarktüsü ile başvurmuş hastaların yüzey EKG’de görülen artmış başlangıç frontal plandaki QRS aksı ile T aksı arasındaki açı (f(QRS/T)) değerinin artmış morbidite ve mortalite ile ilişkili olduğu gösterilmiştir. Ancak akut ST yükselmeli akut miyokard infarktüsünde (STEMİ) revaskülarizasyon sonrası f(QRS/T) değerindeki değişimin değerlendirildiği bir çalışma yoktur. Çalışmamızın amacı, ilk kez akut STEMİ ile başvuran hastalarda f(QRS/T)’yi etkileyecek faktörleri tanımlayarak, bu faktörlerin varlığını klinik ve anjiyografik bulgularla karşılaştırmak ve bu şekilde riskli hastaların belirlenip belirlenmeyeceğini saptamaktır. Ek olarak reperfüzyon tedavisi öncesi ve sonrasındaki açı değerleri arasındaki farkın, reperfüzyon stratejisi ile olan ilişkisi ve hastane içi kötü prognostik olayları öngördürmedeki önemi de incelendi.Çalışma Planı:Çalışmamıza 01/06/2013 ile 31/12/2014 tarihleri arasında DEÜTF (Dokuz Eylül Üniversitesi Tıp Fakültesi) hastanesi koroner yoğun bakıma ilk kez akut STEMİ ile başvuran 248 hasta alındı ve veriler geriye dönük olarak incelendi. Hastaların demografik özellikleri, rutin laboratuar parametreleri kaydedildi. Hastaların 106’sına trombolitik tedavi, 142’sine primer perkutan koroner girişim (PKG) uygulanmıştı. Hastaların koroner yoğun bakım ünitesine yatış anındaki, trombolitik tedavinin başlangıcındaki, trombolitik tedaviden 30-60-90 dakika sonraki ve primer PKG’ giden hastaların ise işlem sonundaki 12 derivasyonlu EKG kayıtlarına ulaşıldı. Elektrokardiyografiler başlangıç f(QRS/T) ve revaskülarizasyon stratejisi sonrasındaki f(QRS/T) yönünden analiz edildi.Bulgular: Başlangıç ortalama f(QRS/T) 74.3°±49.6 idi. Yapılan ROC analizinde başlangıç f(QRS/T) değerinin ≥ 95.6° olması %72.1 özgüllük ve %66.7 duyarlılık ile hastane içi mortaliteyi öngördü. Başlangıç f(QRS/T) değeri ≥ 95.6° olan hastalarda daha yüksek oranda hastane içi mortalite (%16’ya karşın %4.6, p=0.003), proksimal damar hastalığı (%68’e karşın %53.8; p:0.037) ve üç damar hastalığı (%30.7’ye karşın %12.7; p:0.001) saptandı. Ancak MI lokalizasyonu açısından her iki grup arasında anlamlı farklılık tespit edilmedi (anterior Mİ: %48’e karşın %38.7; p:0.174). Bununla beraber, başlangıç f(QRS/T) değeri ≥ 95.6° olan hastaların daha düşük sol ventrikül ejeksiyon fraksiyonuna (LVEF) (%43.6±9.6’ya karşın %47±9.6; p:0.013), daha düşük Hb değerlerine (13.3±1.8’e karşın 13.8±1.7; p:0.024), daha yüksek BUN değerlerine (19.7±11.4’e karşın 16.7±6.8; p:0.042), daha yüksek maksimum Troponin I (TpI) düzeylerine (61.1±33.6’ya karşın 41.3±34; p:<0.001), uzamış QRS sürelerine (93.8±23.7 msn’ye karşın 86.1±17.3 msn; p:0.012 ), daha az ST segment rezolusyonuna (STR) (%53.0±33.8’e karşın %64.3±34.6;p:0.020) sahip olduğu görüldü. Revaskülarizasyon sonrasındaki ortalama f(QRS/T) 60.6°±48.0 idi. Yapılan ROC analizinde revaskülarizasyon sonrası f(QRS/T) değerinin ≥ 89.6° olması ise, %77.8 özgüllük ve %62.5 duyarlılık ile hastane içi mortaliteyi öngördü. Revaskülarizasyon sonrası f(QRS/T) değeri ≥ 89.6° olan hastalarda hastane içi mortalite oranı anlamlı olarak daha fazla iken (%16.9’a karşın %5.3,p=0.011), proksimal damar hastalığı (%67.8’e karşın %55; p=0.083), üç damar hastalığı (%16.9’a karşın %18.5; p=0.785) ve Mİ lokalizasyonu (anterior Mİ oranı: %40.7’ye karşın %41.8; p:0.879) açısından anlamlı farklılık tespit edilmedi. Bununla beraber, revaskülarizasyon sonrası f(QRS/T) değeri ≥ 89.6° olan hastaların daha düşük LVEF’una (%43.3±8.9’a karşın %46.8±9.8; p:0.018), daha yüksek maksimum TpI düzeylerine (55.1±30.1’e karşın 44.8±36.1; p:0.032), daha az oranda STR’una (%50.2±42.4’e karşın %64.0±31.5; p:0.009) sahip olduğu görüldü. Trombolitik tedavi ile rekanalize olan ve rekanalize olmayan hastalar karşılaştırıldığında; ortalama başlangıç f(QRS/T) değeri arasında anlamlı farklılık saptanmazken (78.9°±54.0’e karşın 78.6°±53.4; p=0.976); işlem sonu ortalama f(QRS/T) değeri rekanalize olmayan hasta grubunda (77.3°±52.9’a karşın 53.2°±42.8; p=0.033) daha yüksek olarak tespit edildi. Yapılan çok değişkenli analizde, işlem sonu f(QRS/T) değerinin > 89.6o olması (OR: 3.541, 95% CI: 1.235-10.154, p= 0.019) hastane içi mortalitenin bağımsız prediktörlerinden biri olarak tespit edildi.Sonuç:Akut STEMİ hastalarında başvurudaki artmış f(QRS/T) değeri iskemik tehdit altındaki miyokard alanının daha yaygın olduğunu gösterirken, işlem sonrasındaki artmış f(QRS/T) değeri daha yaygın miyokard alanının nekroza gittiğini gösterir. Bu yüzden işlem sonrası f(QRS/T) değeri LVEF, aritmik olaylar, kardiyovasküler nedenli ölümler ve tüm nedenli ölümler ile daha yakın ilişkilidir. Bununla birlikte, başlangıç f(QRS/T) değerinin ≥ 95.6° olması üç damar hastalığını ve proksimal lezyon varlığını öngördüren bir parametre olarak kullanılabilirken, işlem sonu f(QRS/T) değerinin üç damar hastalığı ve proksimal lezyon varlığı ile herhangi bir ilişkisi yoktur.