RESUMEN
BACKGROUND: Neutrophils are critically involved in the immune response. Inflammatory stimuli alter the expression status of their surface molecule toolset, while inflammation-stimulated granulopoiesis might also influence their maturation status. Data on neutrophil status in heart failure with reduced ejection fraction (HFrEF) are scarce. The present study aims to evaluate the role of neutrophil CD11b, CD66b and CD64 expression in HFrEF. METHODS: A total of 135 HFrEF patients and 43 controls were recruited. Mean fluorescence intensity of the activation/maturation markers CD11b, CD66b and CD64 was measured on neutrophils by flow cytometry. CD10 (neprilysin) expression was simultaneously determined. RESULTS: Neutrophil CD64 expression was higher in HFrEF compared with controls, while CD11b/CD66b levels were similar. Neutrophil CD11b and CD66b showed a significant direct correlation to neutrophil CD10 expression (rs = 0.573, p < 0.001 and rs = 0.184, p = 0.033). Neutrophil CD11b and CD66b correlated inversely with heart failure severity reflected by NT-proBNP and NYHA class (NT-proBNP: rs = -0.243, p = 0.005 and rs = -0.250, p = 0.004; NYHA class: p = 0.032 and p = 0.055), whereas no association for CD64 could be found. Outcome analysis did not reveal a significant association between the expression of CD11b, CD66b and CD64 and all-cause mortality (p = ns). CONCLUSIONS: The results underline the potential role of neutrophils in HFrEF disease pathophysiology and risk stratification and should stimulate further research, characterizing subpopulations of neutrophils and searching for key molecules involved in the downward spiral of inflammation and heart failure.
RESUMEN
BACKGROUND: Angiographic studies have shown that external stenting reduces disease progression in saphenous vein grafts (SVG) for coronary artery bypass grafting (CABG). However, reports of clinical outcomes of external SVG stenting are limited. METHODS: We conducted a retrospective analysis using a prospectively maintained national registry to evaluate clinical outcomes in patients undergoing either isolated CABG or combined (CABG + valve) procedures with use of an external SVG stent between December 2015 and December 2019. Median follow-up was 36.2 months (IQR: 24.4-41.6 months). The primary endpoint was ischemia-driven target vessel revascularization at 1 year. Secondary endpoints included all-cause death, non-fatal myocardial infarction (MI), stroke, and the composite of death, non-fatal MI or stroke at 1 year. Kaplan-Meier rates of survival, freedom from the composite of death, non-fatal MI or stroke and freedom from repeat revascularization were calculated at 3 years. RESULTS: The study population included 74 patients (isolated CABG, N.=61; combined procedure, N.=13). Mean age was 65.5±9.2 years, and 81% were male. External stenting of one SVG was performed in 63 patients (85%) and external stenting of 2 SVG in 11 patients (15%). External stenting was most frequently performed on an SVG to the right coronary artery (N.=45 patients; 53%). Ischemia-driven target-vessel revascularization occurred in 0% at 1 year. All-cause death, MI, stroke, and the composite of death, MI, or stroke at 1 year occurred in 2.7% (2/74), 0% (0/74), 1.4% (1/74), and 4.1% (3/74), respectively. At 3 years, the rates of survival, freedom from the composite of death, non-fatal MI or stroke, and freedom from repeat revascularization were 89.7% (95% CI: 78.0-95.3), 88.3% (95% CI: 76.5-94.4), and 94.8% (95% CI: 84.6-98.3), respectively. CONCLUSIONS: Clinical outcomes with external SVG stenting are excellent without ischemia-driven target-vessel revascularization at 1 year, and low rates of repeat revascularization at 3 years. Further follow-up will show whether external stenting reduces SVG failure with a benefit on long-term clinical outcomes.
Asunto(s)
Infarto del Miocardio , Accidente Cerebrovascular , Anciano , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Estudios Retrospectivos , Vena Safena/trasplante , Stents/efectos adversos , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
Significant expression of neprilysin (NEP) is found on neutrophils, which present the transmembrane integer form of the enzyme. This study aimed to investigate the relationship of neutrophil transmembrane neprilysin (mNEP) with disease severity, adverse remodeling, and outcome in HFrEF. In total, 228 HFrEF, 30 HFpEF patients, and 43 controls were enrolled. Neutrophil mNEP was measured by flow-cytometry. NEP activity in plasma and blood cells was determined for a subset of HFrEF patients using mass-spectrometry. Heart failure (HF) was characterized by reduced neutrophil mNEP compared to controls (p < 0.01). NEP activity on peripheral blood cells was almost 4-fold higher compared to plasma NEP activity (p = 0.031) and correlated with neutrophil mNEP (p = 0.006). Lower neutrophil mNEP was associated with increasing disease severity and markers of adverse remodeling. Higher neutrophil mNEP was associated with reduced risk for mortality, total cardiovascular hospitalizations, and the composite endpoint of both (p < 0.01 for all). This is the first report describing a significant role of neutrophil mNEP in HFrEF. The biological relevance of neutrophil mNEP and exact effects of angiotensin-converting-enzyme inhibitors (ARNi) at the neutrophil site have to be determined. However, the results may suggest early initiation of ARNi already in less severe HF disease, where effects of NEP inhibition may be more pronounced.