RESUMEN
BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).
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Compuestos de Bencidrilo , Glucósidos , Insuficiencia Cardíaca , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico , Humanos , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Enfermedad Aguda , Insuficiencia Cardíaca/tratamiento farmacológico , DiuréticosRESUMEN
Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of, life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure and its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.
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Anemia Ferropénica , Insuficiencia Cardíaca , Deficiencias de Hierro , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/epidemiología , HierroRESUMEN
Despite advances in heart failure therapies with proven positive outcomes, treatment gaps in clinical practice persist and heart failure morbidity and mortality remain high. The lack of treatment intensification to evidence-based targets accounts for a significant portion of unattained treatment goals and has been characterized to involve 3 main elements: the provider initiating and titrating the medication(s), the patient themselves, and the system that serves as the gatekeeper and facilitator for health care needs. This article will examine the mechanisms and impact of these 3 factors, and present targeted initiatives to help improve patient outcomes and quality of care.
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Insuficiencia Cardíaca , Insuficiencia Cardíaca/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure. OBJECTIVE: The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care. METHODS: DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality. CONCLUSIONS: The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.
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Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Enfermedad Aguda , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Cetoacidosis Diabética , Progresión de la Enfermedad , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/metabolismo , Mortalidad Hospitalaria , Humanos , Hiperglucemia , Hipoglucemia , Hipoglucemiantes/uso terapéutico , Hipotensión , Hipovolemia , Insulina/uso terapéutico , Natriuresis , Péptido Natriurético Encefálico/metabolismo , Readmisión del Paciente , Fragmentos de Péptidos/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/complicaciones , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Heart failure (HF) prevalence continues to rise and remains a significant burden to patients, caregivers, providers, and the healthcare system. Guideline-directed medical therapy with standard neurohormonal blockade has been the cornerstone of medical management for many years. Despite aggressive utilization of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists, HF hospitalizations and readmissions are common and residual mortality remains high. With the development of two novel medical therapies (sacubitril/valsartan and ivabradine), the American College of Cardiology, American Heart Association, and Heart Failure Society of America released a pharmacologic update to provide guidelines for incorporation of these agents into clinical practice. Although effective via different mechanisms of action, both agents now have a prominent role in risk reduction. HF medical regimens often become quite complex, especially when associated with comorbid conditions, and require frequent follow-up. Providers must be proficient in patient monitoring, medication dose titration, and therapy optimization. Individualized patient care strategies such as guideline-directed therapy can promote long-term adherence and quality of life.
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Insuficiencia Cardíaca/enfermería , Guías de Práctica Clínica como Asunto , Humanos , Resultado del TratamientoRESUMEN
Orofacial clefts are among the most common birth defects and result in an improper formation of the mouth or the roof of the mouth. Monosomy of the distal aspect of human chromosome 6p has been recognized as causative in congenital malformations affecting the brain and cranial skeleton including orofacial clefts. Among the genes located in this region is PAK1IP1, which encodes a nucleolar factor involved in ribosomal stress response. Here, we report the identification of a novel mouse line that carries a point mutation in the Pak1ip1 gene. Homozygous mutants show severe developmental defects of the brain and craniofacial skeleton, including a median orofacial cleft. We recovered this line of mice in a forward genetic screen and named the allele manta-ray (mray). Our findings prompted us to examine human cases of orofacial clefting for mutations in the PAK1IP1 gene or association with the locus. No deleterious variants in the PAK1IP1 gene coding region were recognized, however, we identified a borderline association effect for SNP rs494723 suggesting a possible role for the PAK1IP1 gene in human orofacial clefting.
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Cromosomas Humanos Par 6 , Labio Leporino/genética , Fisura del Paladar/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Proteínas Nucleares/genética , Translocación Genética , Alelos , Secuencia de Aminoácidos , Animales , Puntos de Rotura del Cromosoma , Mapeo Cromosómico , Labio Leporino/patología , Fisura del Paladar/patología , Femenino , Homocigoto , Humanos , Masculino , Ratones , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Isoformas de Proteínas/genéticaRESUMEN
Most infective processes are straightforward and can be diagnosed from bacterial findings in a single test. IE does not always follow this tenet, so establishing the diagnosis can be difficult. The salient features of IE may present atypically or be obscured by the presence of preexisting and coexisting diseases. Flulike symptoms may mask the beginning of this devastating disease. Early diagnosis of IE is important because of its high risk of morbidity and mortality. Management of the patient who has IE is complex and requires interventions by infectious disease specialists, cardiologists, respiratory therapists, and critical care nurses to address the many multifaceted complications. Early evaluation, diagnostic validation, multidisciplinary management, prompt pharmaceutical initiation, and intense critical care nursing intervention are necessary to reduce the probability of long-standing complications and to improve patient outcomes.
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Endocarditis Bacteriana/terapia , Cuidados Críticos , Ecocardiografía Transesofágica , Embolia/etiología , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/enfermería , Insuficiencia Cardíaca/etiología , Humanos , Rol de la Enfermera , Infarto del Bazo/etiologíaRESUMEN
Heart transplantation can be a lifesaving option for patients with end-stage heart failure. However, implanting recipients with an organ or tissue from a donor presents immunologic challenges. Sensitized recipients are at risk for hyperacute rejection because of the presence of preformed antibodies. Immune modulation with cyclophosphamide, plasmapheresis, and intravenous gamma globulin are methods used to desensitize transplant candidates with preformed anti-HLA antibodies to achieve successful transplantation.