RESUMO
Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease characterized by the progressive elevation of pulmonary arterial pressures. It is becoming increasingly apparent that inflammation contributes to the pathogenesis and progression of PAH. Several viruses are known to cause PAH, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human endogenous retrovirus K(HERV-K), and human immunodeficiency virus (HIV), in part due to acute and chronic inflammation. In this review, we discuss the connections between HERV-K, HIV, SARS-CoV-2, and PAH, to stimulate research regarding new therapeutic options and provide new targets for the treatment of the disease.
Assuntos
COVID-19 , Retrovirus Endógenos , Infecções por HIV , Hipertensão Arterial Pulmonar , Humanos , HIV , SARS-CoV-2 , Hipertensão Pulmonar Primária Familiar , InflamaçãoRESUMO
Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)-associated PH and pulmonary arterial hypertension (PAH). Cis-expression quantitative trait loci (eQTL) were queried for RASA3 using whole genome genotype arrays and gene expression profiles derived from peripheral blood mononuclear cells (PBMC) of three SCD cohorts. Genome-wide single nucleotide polymorphisms (SNPs) near or in the RASA3 gene that may associate with lung RASA3 expression were identified, reduced to 9 tagging SNPs for RASA3 and associated with markers of PH. Associations between the top RASA3 SNP and PAH severity were corroborated using data from the PAH Biobank and analyzed based on European or African ancestry (EA, AA). We found that PBMC RASA3 expression was lower in patients with SCD-associated PH as defined by echocardiography and right heart catheterization and was associated with higher mortality. One eQTL for RASA3 (rs9525228) was identified, with the risk allele correlating with PH risk, higher tricuspid regurgitant jet velocity and higher pulmonary vascular resistance in patients with SCD-associated PH. rs9525228 associated with markers of precapillary PH and decreased survival in individuals of EA but not AA. In conclusion, RASA3 is a novel candidate gene in SCD-associated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.
RESUMO
The efficiency of blood flowing from the heart depends on its electrical properties. Myocardial electrical activity is associated with generating cardiac action potentials in isolated myocardial cells and their coordinated propagation, which are mediated by gap junctions. Atrial fibrillation (AF) is a common cardiac arrhythmia which causes an aggressive disturbance in cardiac electromechanical function. Moreover, AF increases the risk of stroke and mortality and is a major cause of death. The mechanisms underlying AF involve electrophysiological changes in ion channel expression and function. ß-blockers may be useful in patients with chronic AF or in preventing postoperative AF in subjects undergoing coronary artery bypass grafting (CABG) or other types of surgery. The reduction in heart rate induced by ß1-adrenergic receptor antagonists may be associated with the beneficial effect of this drug class. Second generation beta-blockers may be considered superior to the first generation due to their selectivity to the ß1 receptor as well as avoiding pulmonary or metabolic adverse effects. Third generation beta-blockers may be considered a great option for their vasodilation and antioxidant properties. There is also a new ß-blocker, named landilol that also results on reduced risk of post operative AF without adverse effects and its use has been increasing in clinical trials.
Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Frequência Cardíaca , Ponte de Artéria Coronária/efeitos adversos , MiocárdioRESUMO
PURPOSE OF REVIEW: Sickle cell disease (SCD), one of the most common genetic diseases in the world, is characterized by repeated episodes of hemolysis and vaso-occlusion. Hemolytic anemia is a risk factor for the development of pulmonary hypertension, and currently SCD-related pulmonary hypertension is classified as World Health Organization group 5 pulmonary hypertension. Patients with SCD-related pulmonary hypertension have unique hemodynamics, multiple comorbidities, and distinct phenotypes that may contribute to the development of pulmonary hypertension. RECENT FINDINGS: SCD-related pulmonary hypertension is defined as a mean pulmonary artery pressure >20âmmHg, a pulmonary artery occlusion pressure ≤15âmmHg and relatively low pulmonary vascular resistance (>2 Wood units) rather than the traditional definition of ≥3 Wood units, an important distinction due to a baseline high-cardiac output state in the setting of chronic anemia and low vascular resistance. Diastolic dysfunction is frequently identified in this patient population and right heart catheterization is essential to determine if combined pre- and postcapillary pulmonary hypertension is present. Thromboembolism is common among patients with SCD, and screening for chronic thromboembolic pulmonary hypertension is essential. Data regarding advanced therapies are limited. Primary treatment options include targeting correction of their primary hemoglobinopathy as well as aggressive management of underlying comorbid conditions. SUMMARY: SCD-related pulmonary hypertension is common among patients with SCD and is associated with increased mortality. A high index of suspicion is warranted during evaluation to identify all potential factors that may be contributing to disease.
Assuntos
Anemia Falciforme , Hipertensão Pulmonar , Anemia Falciforme/complicações , Cateterismo Cardíaco , Hemodinâmica , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Pressão Propulsora PulmonarRESUMO
BACKGROUND: Timely initiation of physical, occupational, and speech therapy in critically ill patients is crucial to reduce morbidity and improve outcomes. Over a 5-year time interval, we sought to determine the utilization of these rehabilitation therapies in the USA. METHODS: We performed a retrospective cohort study utilizing a large, national administrative database including ICU patients from 591 hospitals. Patients over 18 years of age with acute respiratory failure requiring invasive mechanical ventilation within the first 2 days of hospitalization and for a duration of at least 48 h were included. RESULTS: A total of 264,137 patients received invasive mechanical ventilation for a median of 4.0 [2.0-8.0] days. Overall, patients spent a median of 5.0 [3.0-10.0] days in the ICU and 10.0 [7.0-16.0] days in the hospital. During their hospitalization, 66.5%, 41.0%, and 33.2% (95% CI = 66.3-66.7%, 40.8-41.2%, 33.0-33.4%, respectively) received physical, occupational, and speech therapy. While on mechanical ventilation, 36.2%, 29.7%, and 29.9% (95% CI = 36.0-36.4%, 29.5-29.9%, 29.7-30.1%) received physical, occupational, and speech therapy. In patients receiving therapy, their first physical therapy session occurred on hospital day 5 [3.0-8.0] and hospital day 6 [4.0-10.0] for occupational and speech therapy. Of all patients, 28.6% (95% CI = 28.4-28.8%) did not receive physical, occupational, or speech therapy during their hospitalization. In a multivariate analysis, patients cared for in the Midwest and at teaching hospitals were more likely to receive physical, occupational, and speech therapy (all P < 0.05). Of patients with identical covariates receiving therapy, there was a median of 61%, 187%, and 70% greater odds of receiving physical, occupational, and speech therapy, respectively, at one randomly selected hospital compared with another (median odds ratio 1.61, 2.87, 1.70, respectively). CONCLUSIONS: Physical, occupational, and speech therapy are not routinely delivered to critically ill patients, particularly while on mechanical ventilation in the USA. The utilization of these therapies varies according to insurance coverage, geography, and hospital teaching status, and at a hospital level.