Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.     

Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee

Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials.     

Stroke and the “Stroke Belt” in Dialysis: Contribution of Patient Characteristics to Ischemic Stroke Rate and Its Geographic Variation

Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m² was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the “stroke belt” or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients.Stroke is a catastrophic health event and a leading cause of disability. It represents a particularly heavy burden for the long-term dialysis population, in whom stroke rates are substantially higher than in the general population.¹ In the general population, there is substantial geographic variability in stroke rates, with the southeastern United States having long been recognized as a “stroke belt” of higher stroke mortality rates.^2–4 However, whether a stroke belt of increased ischemic stroke incidence exists in dialysis patients has not been formally studied.Although one might suspect that the same factors contributing to ischemic stroke risk in the general population also apply to dialysis patients, there are several reasons to posit that this might not be the case. First, unlike the general population, dialysis patients across the United States have consistent access to insurance and frequent contact with health care providers, who routinely measure their BP, irrespective of geographic location. Second, the nature of vascular disease differs between dialysis and nondialysis patients, so different pathophysiologic mechanisms may be operative in the two populations.⁵ Third, dialysis patients fundamentally represent a “survivor cohort” relative to individuals with (predialysis) CKD and its attendant cardiovascular disorders, suggesting that epidemiologic trends evident in one population might not be found in the other.⁶ Accordingly, it is uncertain whether there is substantial geographic variation in stroke risk among dialysis patients and what factors might, in part, explain such a finding.To address this gap in knowledge, we constructed a large cohort of incident dialysis patients to determine whether ischemic stroke rates vary by geography and how differences in stroke rates might be explained by patient characteristics. We reasoned that uncovering the existence of geographic variability in the stroke rates of dialysis patients might provide direction for focused health care efforts in regions at elevated risk, such as screening new dialysis patients for symptoms that might be referable to old strokes, lowering the threshold for investigating cerebrovascular disease, or educating dialysis patients on the importance of seeking immediate care for stroke-type symptoms.     

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r²=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Native aortic valve tissue systemic embolization complicating bacterial endocarditis

Systemic embolic events are known complications of bacterial endocarditis. Embolization of prosthetic valves has previously been reported in the literature. We report a case of embolization of native aortic valve tissue to the popliteal artery as the presenting event in a patient with subacute bacterial endocarditis. To our knowledge, this rare complication has not been previously reported.