RESUMEN
BACKGROUND: Value-based healthcare (VBHC) is an approach that focuses on delivering the highest possible value for patients while driving cost efficiency in health services. It emphasizes improving patient outcomes and experiences while optimizing the use of resources, shifting the healthcare system's focus from the volume of services to the value delivered. Our study assessed the effectiveness of implementing a VBHC-principled, tailored preoperative evaluation in enhancing patient care and outcomes, as well as reducing healthcare costs. METHODS: We employed a quality improvement, before-and-after approach to assessing the effects of implementing VBHC strategies on the restructuring of the preoperative evaluation clinics at Humanitas Research Hospital. The intervention introduced a VBHC-tailored risk matrix during the postintervention phase (year 2021), and the results were compared with those of the preintervention phase (2019). The primary study outcome was the difference in the number of preoperative tests and visits at baseline and after the VBHC approach. Secondary outcomes were patient outcomes and costs. RESULTS: A total of 9722 patients were included: 5242 during 2019 (baseline) and 4,480 during 2021 (VBHC approach). The median age of the population was 63 (IQR 51-72), 23% of patients were classified as ASA 3 and 4, and 26.8% (2,955 cases) were day surgery cases. We found a considerable decrease in the number of preoperative tests ordered for each patient [6.2 (2.5) vs 5.3 (2.6) tests, p < 0.001]. The number of preoperative chest X-ray, electrocardiogram, and cardiac exams decreased significantly with VBHC. The length of the preoperative evaluation was significantly shorter with VBHC [373 (136) vs 290 (157) min, p < 0.001]. Cost analysis demonstrated a significant reduction in costs, while there was no difference in clinical outcomes. CONCLUSIONS: We demonstrated the feasibility, safety, and cost-effectiveness of a tailored approach for preoperative evaluation. The implementation of VBHC enhanced value, as evidenced by decreased patient time in preoperative evaluation and by a reduction in unnecessary preoperative tests.
RESUMEN
Pesticides has transformed the agricultural industry, primarily by enhancing productivity. However, the indiscriminate use of such compounds can adversely affect human health and disrupt ecosystem balance. Limited knowledge exists regarding the removal of these compounds from water, particularly for organophosphate pesticides when employing conventional treatment technologies. Therefore, this study aimed to assess the removal of acephate (ACE) and methamidophos (MET) - considered priority pesticides in Brazil - from waters with high and low turbidity during the clarification process carried out with aluminum sulfate (AS) and ferric chloride (FC), either alone or combined with powdered activated carbon (PAC) adsorption. All water samples were submitted to solid phase extraction (SPE C18 cartridges) prior to acephate and methamidophos analysis by HPLC MS/MS. The clarification process with either AS or FC coagulant did not efficiently remove acephate or methamidophos and maximum average removal (27 %) was observed with waters of high turbidity when using ferric chloride as coagulant. Addition of mineral PAC was also ineffective for removing both pesticides. However, the use of vegetable PAC (10 mg/L) resulted in better removal percentages, up to 80%, but only for methamidophos. The limited removal rates were attributed to the high hydrophilicity of acephate and methamidophos, along with their neutral charge at coagulation pH. These factors hinder the interaction of such organophosphorus pesticides with the flocs formed during coagulation as well as with PAC surface.
RESUMEN
BACKGROUND AND AIMS: Measuring 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone 1-84 (PTH 1-84) and intact FGF23 (iFGF23) is crucial for diagnosing a variety of diseases affecting bone and mineral homeostasis. Biological variability (BV) data are important for defining analytical quality specifications (APS), the usefulness of reference intervals, and the significance of variations in serial measurements in the same subject. The aim of this study was to pioneer the provision of BV estimates for 1,25(OH)2D and to improve existing BV estimates for iFGF23 and PTH 1-84. MATERIALS AND METHODS: Serum and plasma-EDTA samples of sixteen healthy subjects have been collected for seven weeks and measured in duplicate by chemiluminescent immunoassay on the DiaSorin Liaison platform. After variance verification, within-subject (CVI) and between-subject (CVG) BV estimates were assessed by either standard ANOVA, or CV-ANOVA. The APSs were calculated according to the EFLM-BV-model. RESULTS: We found the following CVI estimates with 95% confidence intervals:1,25(OH)2D, 22.2% (18.9-26.4); iFGF23, 16.1% (13.5-19.5); and PTH 1-84, 17.9% (14.8-21.8). The CVG were: 1,25(OH)2D, 21.2% (14.2-35.1); iFGF23, 21.1% (14.5-35.8); and PTH 1-84, 31.1% (22.1-50.8). CONCLUSIONS: We report for the first time BV estimates for 1,25(OH)2D and enhance existing data about iFGF23-BV and PTH 1-84-BV through cutting-edge immunometric methods.
Asunto(s)
Factor-23 de Crecimiento de Fibroblastos , Vitamina D/análogos & derivados , Humanos , Hormona Paratiroidea , Voluntarios SanosRESUMEN
We report a unique case of cervical anterior spinal artery (ASA) infarction in a 49-year-old male with hypercholesterolemia and sleep apnea. The patient experienced sudden cervical pain, quadriparesis, areflexia, and urinary incontinence after swallowing a large food bolus. Imaging revealed an infarction at the C3-C5 levels and an anomalous right vertebral artery (VA) originating from the thoracic aorta, tightly enclosed between the aorta and a vertebral column with an anterior osteophyte. This aberrant VA was the primary vascular supply to the ASA, with no contribution from the left VA or supreme intercostal arteries. We propose that transient injury to the right VA, induced by compression between the aortic arch, the food bolus, and the osteophyte, led to temporary hypoperfusion of the ASA, causing a watershed ischemic injury in the mid cervical cord's anterior gray matter. The article also provides an in-depth discussion of the developmental and clinical characteristics associated with this rare vascular anomaly.
Asunto(s)
Osteofito , Malformaciones Vasculares , Masculino , Humanos , Persona de Mediana Edad , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/anomalías , Cuello , Vértebras Cervicales/diagnóstico por imagen , Infarto/diagnóstico por imagen , Infarto/etiologíaRESUMEN
Tebuconazole is a triazole fungicide widely used in agricultural crops for control of multiple fungal, mainly foliar and soil-borne diseases. Due to its intense use, this pesticide has been detected on aquatic matrices in different countries, which makes it necessary to identify metabolites capable to be used in its exposure monitoring. The aim of this work was to evaluate tebuconazole metabolites in zebrafish water tanks using liquid chromatography coupled to a high-resolution mass spectrometer (LCHRMS) to highlight analytical targets to monitor tebuconazole exposure in aquatic environments. Two Phase I metabolites, TEB-OH and TEB-COOH, and one Phase II metabolite, TEB-S, were identified. Target metabolomics pointed TEB-S as the most important metabolite for discrimination between treatment and negative control group and potential surrogate for detection and monitoring of tebuconazole exposure in aquatic environments. To the best of our knowledge, this is the first study to suggest the sulphation of tebuconazole (TEB-S) by zebrafish metabolism. Moreover, the use of water samples proved to be a promising approach when compared to the usual biological matrices (e.g. plasma) for evaluating the exposure of aquatic animals to tebuconazole because it is a clean and easy to obtain matrix. Water samples presented a higher concentration of metabolites when compared to plasma samples. The results suggest the applicability of this assay model for the identification of potential biomarkers for monitoring the presence of xenobiotics in water.
Asunto(s)
Fungicidas Industriales , Contaminantes Químicos del Agua , Animales , Fungicidas Industriales/toxicidad , Fungicidas Industriales/química , Pez Cebra/metabolismo , Contaminantes Químicos del Agua/toxicidad , Triazoles/química , Biotransformación , AguaRESUMEN
Heart failure with reduced ejection fraction is a chronic and progressive syndrome that continues to be a substantial financial burden for health systems in Western countries. Despite remarkable advances in pharmacologic and device-based therapy over the last few years, patients with heart failure with reduced ejection fraction have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Worsening heart failure episodes represent a critical event in the heart failure trajectory, carrying high residual risk at discharge and dismal short- or long-term prognosis. Recently, vericiguat, a soluble guanylate cyclase stimulator, has been proposed as a novel drug whose use is already associated with a reduction in heart failure-related hospitalizations in patients in guideline-directed medical therapy. In this review, we summarized the pathophysiology of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate cascade in patients with heart failure with reduced ejection fraction, the pharmacology of vericiguat as well as the evidence regarding their use in patients with HFrEF. Finally, tips and tricks for its use in standard clinical practice are provided.
RESUMEN
In recent years, a significant improvement in left ventricular assist device (LVAD) technology has occurred, and the continuous-flow devices currently used can last more than 10 years in a patient. Current studies report that the 5-year survival rate after LVAD implantation approaches that after a heart transplant. However, the outcome is influenced by the correct selection of the patients, as well as the choice of the optimal time for implantation. This review summarizes the indications, the red flags for prompt initiation of LVAD evaluation, and the principles for appropriate patient screening.
RESUMEN
Cardiac transplantation represents the gold standard of treatment for selected patients with advanced heart failure who have poor functional capacity and prognosis despite guideline-directed medical therapy and device-based therapy. Proper patient selection and appropriate referral of patients to centers for the treatment of advanced heart failure are the first but decisive steps for screening patients eligible for cardiac transplantation. The eligibility and the decision to list for cardiac transplantation, even for patients with relative contraindications, are based on a multidisciplinary evaluation of a transplant team. This review will discuss the practical indications, the process of patient eligibility for cardiac transplantation, the principle of donor selection, as well as the surgical technique.
RESUMEN
Even though acute heart failure (AHF) is one of the most common admission diagnoses globally, its pathogenesis is poorly understood, and there are few effective treatments available. Despite an heterogenous onset, congestion is the leading contributor to hospitalization, making it a crucial therapeutic target. Complete decongestion, nevertheless, may be hard to achieve, especially in patients with reduced end organ perfusion. In order to promote a personalised pathophysiological-based therapy for patients with AHF, we will address in this review the pathophysiological principles that underlie the clinical symptoms of AHF as well as examine how to assess them in clinical practice, suggesting that gaining a deeper understanding of pathophysiology might result in significant improvements in HF therapy.
RESUMEN
Carbendazim is a systemic fungicide used in several countries, particularly in Brazil. However, studies suggest that it is related to the promotion of tumors, endocrine disruption, and toxicity to organisms, among other effects. As a result, carbendazim is not allowed in the United States, Australia, and some European Union countries. Therefore, further studies are necessary to evaluate its effects, and zebrafish is a model routinely used to provide relevant information regarding the acute and long-term effects of xenobiotics. In this way, zebrafish water tank samples (water samples from aquari containing zebrafish) and liver samples from animals exposed to carbendazim at a concentration of 120 µg/L were analyzed by liquid chromatography coupled to high-resolution mass spectrometry, followed by multivariate and univariate statistical analyses, using the metabolomics approach. Our results suggest impairment of lipid metabolism with a consequent increase in intrahepatic lipids and endocrine disruption. Furthermore, the results suggest two endogenous metabolites as potential biomarkers to determine carbendazim exposure. Finally, the present study showed that it is possible to use zebrafish water tank samples to assess the dysregulation of endogenous metabolites to understand biological effects. Environ Toxicol Chem 2023;42:437-448. © 2022 SETAC.
Asunto(s)
Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Metabolómica/métodos , Hígado , Lípidos , Agua/metabolismoRESUMEN
BACKGROUND: Cardiac contractility modulation (CCM) is an innovative therapy for heart failure with reduced ejection fraction delivered by a cardiac implantable device (Optimizer Smart®). One of the most prominent periprocedural complications common to all cardiac implantable devices (CIDs) is tricuspid regurgitation (TR) due to the placement of the right ventricular endocardial leads. To date, no published studies have assessed the changes in the TR degree in patients with heart failure with reduced ejection fraction (HFrEF) who received an implantable cardioverter-defibrillator (ICD) after the implantation of cardiac contractility modulation therapy devices. OBJECTIVE: This study aimed to evaluate the effect of the implantation of the trans-tricuspid leads required to deliver CCM therapy on the severity of TR in patients with HFrEF who previously underwent ICD implantation. METHODS: We enrolled 30 HFrEF patients who underwent CCM therapy between November 2020 and October 2021. For all the patients, echocardiographic evaluations of TR were performed according to current guidelines 24 h before and six months after the Optimizer Smart® implant was applied. RESULTS: At the 6-month follow-up, the grade of TR remained unchanged compared to the preimplant grade. The value of the vena contracta (VC) of TR was 0.40 ± 0.19 cm in the preimplant period and 0.45 ± 0.21 cm at the 6-month follow-up (p = 0.33). Similarly, the TR proximal isovelocity surface area (PISA) radius value was unchanged at follow-up (0.54 ± 0.22 cm vs. 0.62 ± 0.20 cm; p = 0.18). No statistically significant difference existed between the preimplant VC and PISA radius values, irrespective of the device type. CONCLUSIONS: The implantation of right ventricular electrodes for the delivery of CCM therapy did not worsen tricuspid regurgitation in patients with HFrEF and ICD.
RESUMEN
BACKGROUND: Virtually all patients with heart failure with reduced ejection fraction have a reduction of myocardial mechano-energetic efficiency (MEE). Cardiac contractility modulation (CCM) is a novel therapy for the treatment of patients with HFrEF, in whom it improves the quality of life and functional capacity, reduces hospitalizations, and induces biventricular reverse remodeling. However, the effects of CCM on MEE and global longitudinal strain (GLS) are still unknown; therefore, this study aims to evaluate whether CCM therapy can improve the MEE of patients with HFrEF. METHODS: We enrolled 25 patients with HFrEF who received an Optimizer Smart implant (the device that develops CCM therapy) between January 2018 and January 2021. Clinical and echocardiographic evaluations were performed in all patients 24 h before and six months after CCM therapy. RESULTS: At six months, follow-up patients who underwent CCM therapy showed an increase of left ventricular ejection fraction (30.8 ± 7.1 vs. 36.1 ± 6.9%; p = 0.032) as well a rise of GLS 10.3 ± 2.7 vs. -12.9 ± 4.2; p = 0.018), of MEE (32.2 ± 10.1 vs. 38.6 ± 7.6 mL/s; p = 0.013) and of MEE index (18.4 ± 6.3 vs. 24.3 ± 6.7 mL/s/g; p = 0.022). CONCLUSIONS: CCM therapy increased left ventricular performance, improving left ventricular ejection fraction, GLS, as well as MEE and MEEi.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The anxiety disorders are the most prevalent mental health condition, and anxiety is considered the sixth cause of disability surpassing diabetes mellitus, chronic obstructive pulmonary disease, and osteoarthritis. Besides, the COVID-19 pandemic provided an increase in the number of psychiatric diseases diagnosis in all social layers around the world. About 55%-94% of patients diagnosed with anxiety disorders are treated with benzodiazepines, meanwhile benzodiazepines can promote several adverse effects. In this way, alternative therapies, such as essential oils may offer significant benefits in the treatment of patients with anxiety disorders. However, the anxiolytic effect of these essential oils must be proper evaluated appropriate as well as the suitable dosage and side effect need further research. AIM OF THE STUDY: The aim was to evaluate the anxiolytic effect of Roman chamomile (Anthemis nobilis L.) and tangerine (Citrus reticulata Blanco) essential oils using the light-dark test in adult zebrafish (Danio rerio). MATERIAL AND METHODS: Both essential oils were analyzed by GC-MS and the major compounds were identified. The anxiolytic effect was evaluated by light-dark test in adult zebrafish. RESULTS: The results showed that roman chamomile essential oil has anxiolytic effect in adult zebrafish, whereas tangerine essential oil tends to reduce anxiety The major compounds of tangerine essential oil were limonene and γ-terpinene, and the major compounds of roman chamomile were pentadecyl-3-methyl-2-butenoate, hexadecyl-3-methyl-2-butenoate, 1-piperidinol and trans-1-ethyl-3-methyl-cyclopentane. CONCLUSIONS: The present study demonstrated that this anxiolytic effect may be attributed to the synergistic effect of the compounds present in roman chamomile essential oil, particularly the major compounds. The roman chamomile essential oil at the highest concentration showed anxiolytic effect. The tangerine essential oil showed a tendency to reduce anxiety, but it was not statistically significative. In addition, roman chamomile and tangerine essential oils did not cause cause alteration in locomotion activity and exploratory ability of the fish.
Asunto(s)
Ansiolíticos , COVID-19 , Citrus , Aceites Volátiles , Animales , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Benzodiazepinas , Chamaemelum , Manzanilla , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Pandemias , Pez CebraRESUMEN
Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of ß-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients.
RESUMEN
Background: The COVID-19 pandemic has strongly impacted on healthcare services' organization and healthcare workers' mental health, increasing the risk of psychological symptoms and burnout. Italy has been one of the most affected countries, especially the northern regions, even with exceptions in some rural provinces. Aim: We chose to investigate the mental health conditions of healthcare workers operating in the rural province of Rovigo (a small town in Veneto, northern Italy), where relatively few deaths and contagions were reported during the pandemic, even if Veneto-globally-was one of the most affected regions of Italy. We wanted to verify the psychological outcomes of health workers operating in a context where the impact of the pandemic appeared to be relatively mild. Methods: Through an online survey, we investigated perceived difficulties at work and in daily life, perceived loneliness and social support, coping strategies, and level of psychological distress (sample size: 749; mean age = 48.04 years, SD = 10.66). The questionnaire had both open- (2) and close-ended questions (5 single-choice and 13 multiple-choice). We verified possible associations between sex, age group, work department and percentage of responses with chi-square tests of independence on each question. Data cleaning excluded all contradictory answers from the multiple-choice questions from the analyses (final sample size: 640). Results: Frontliners and non-frontliners reported a similar experience of the COVID-19 pandemic (without significant differences in perceived difficulties, coping strategies and sources of support). Nevertheless, they still reported various forms of negative emotions (e.g., helplessness-40.94%; sadness-36.56%; frustration-32.66%) and lack of support from the health organization (especially frontliners-28.72%). However, psychological help was scarcely requested. Conclusions: Despite the province not being massively affected by the pandemic, healthcare workers felt the need for clearer and more supportive guidance. They seem to perceive collective opportunities to share needs and difficulties as more useful than individual interventions (as those provided by the ad hoc created listening service).
Asunto(s)
Agotamiento Profesional , COVID-19 , Agotamiento Profesional/epidemiología , Personal de Salud , Humanos , Persona de Mediana Edad , Pandemias , SARS-CoV-2RESUMEN
ABSTRACT: Infusions of levosimendan delivered in ambulatory/outpatient settings have been shown to improve quality of life and reduce hospitalizations in patients with advanced heart failure (HF). The aim of this pilot study was to evaluate the effects of ambulatory infusion of levosimendan on echocardiographic markers of perfusion, congestion, and cardiovascular efficiency. Thirty patients with diagnosed advanced HF underwent ambulatorial infusion of levosimendan at a total dose of 6.25 mg as a part of a repetitive biweekly treatment strategy with the inotrope. Standardized transthoracic echocardiography and Doppler examinations, were performed 1 hour before and 48 hours after completion of ambulatory infusion. At 48 hours after ambulatory infusion of levosimendan, a significant increase in the stroke volume (37.47 ± 12.38 mL/beat vs. 45.47 ± 14.48 mL/beat; P < 0.05) and cardiac output (2.64 ± 0.66 L/min vs. 3.26 ± 0.57 L/min; P < 0.05) occurred. Significant postreductions versus prereductions were also recorded in left atrial pressure (27.37 ± 6.62 mm Hg vs. 22.82 ± 4.17 mm Hg; P < 0.01), mean pulmonary artery pressure (27.69 ± 4.64 mm Hg vs. 23.24 ± 5.32; P < 0.01), and inferior vena cava diameter (23.81 ± 7.63 mm vs. 18.53 ± 4.82 mm; P < 0.01). Significant improvements were noted in the resting cardiac power output (0.46 ± 0.15 watt vs. 0.53 ± 0.22 watt; P < 0.01) and the resting cardiac power index (0.24 ± 0.08 watt/m2 vs. 0.28 ± 0.11 watt/m2; P < 0.01). In outpatients with advanced HF, infusion of levosimendan was associated with hemodynamic responses that may contribute to the clinical benefit previously reported in such patients.
Asunto(s)
Fármacos Cardiovasculares/administración & dosificación , Ecocardiografía Doppler , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Simendán/administración & dosificación , Anciano , Atención Ambulatoria , Fármacos Cardiovasculares/efectos adversos , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Proyectos Piloto , Valor Predictivo de las Pruebas , Recuperación de la Función , Simendán/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Aim: An online survey was proposed to the health workers of a public hospital of an Italian northern city. This was done with the aim of assessing the unmet needs of a special population under strain (the health carers) due to the fight against the coronavirus disease 19 (COVID-19). Results: By answering the survey, five hundred and nine people provided their observations, complaints and suggestions. This qualitative material was organised into three main areas: (1) relationship with the health organization management; (2) needs of the health workers; and (3) perceived consequences of the pandemic. Discussion: Overall, respondents expressed dissatisfaction for the unpreparedness of their health units and the confusion created by frequent changes in operational guidelines. Many participants felt abandoned, unheard and unprotected by the health organization, whilst the psychological support service formally set up by the hospital for its health workers was grossly under-utilised. Instead, support from colleagues and family constituted the main protective factor to counteract negative emotions. Restrictions in social contacts and recreational opportunities were frequently mentioned. Several respondents reported a sense of pride for their work and commitment; many others saw in the pandemic an opportunity for personal growth and better focus on important life values, like family and solidarity.
Asunto(s)
COVID-19 , Pandemias , Cuidadores , Personal de Salud , Humanos , Italia/epidemiología , SARS-CoV-2RESUMEN
Treatment with ß-blockers is the main strategy for managing patients with heart failure and reduced ejection fraction because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with consequent prognostic and symptomatic benefits. However, to date, they are underused, mainly because of the misconception that hypotension and bradycardia may worsen the haemodynamic status of patients with HFrEF and because of the presence of comorbidities falsely believed to be absolute contraindications to their use. To promote proper use of ß-blockers in this article, we review the clinical pharmacology of ß-blockers, the evidence of the beneficial effects of these drugs in heart failure with reduced ejection fraction, and the current guidelines for their use in clinical practice and in the presence of comorbidities (e.g., pulmonary disease, diabetes, atrial fibrillation, peripheral arterial disease, etc.). It is hoped that the practical approach discussed in this review will allow for a proper diffusion of knowledge about the correct use of ß-blockers and the drug-disease interactions to achieve their increased use and titration, as well as for the selection of a specific agent with a view to a properly tailored approach for HFrEF patients.
RESUMEN
Patients with advanced heart failure suffer from severe and persistent symptoms, often not responding disease-modifying drugs, a marked limitation of functional capacity and poor quality of life that can ameliorate with inotropic drugs therapy. In small studies, pulsed infusions of classical inotropes (ie, dobutamine and milrinone) are associated with improvement in hemodynamic parameters and quality of life in patients with advanced heart failure. However, because of the adverse effects of these drugs, serious safety issues have been raised. Levosimendan is a calcium-sensitizing inodilators with a triple mechanism of action, whose infusion results in hemodynamic, neurohormonal, and inflammatory cytokine improvements in patients with chronic advanced HF. In addition, levosimendan has important pleiotropic effects, including protection of myocardial, renal, and liver cells from ischemia-reperfusion injury, and anti-inflammatory and antioxidant effects; these properties possibly make levosimendan an "organ protective" inodilator. In clinical trials and real-world evidence, infusion of levosimendan at fixed intervals is safe and effective in patients with advanced HF, alleviating clinical symptoms, reducing hospitalizations, and improving the quality of life. Therefore, the use of repeated doses of levosimendan could represent the therapy of choice as a bridge to transplant/left ventricular assist device implantation or as palliative therapy in patients with advanced heart failure.