Clinical Course Long After Atrial Switch: A Novel Risk Score for Major Clinical Events

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Sacubitril/valsartan in the treatment of systemic right ventricular failure

Objective: Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients. Methods: Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment. Results: Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively). Conclusions: We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population

Neuroinflammation in bipolar disorder:A [C-11]-(R)-PK11195 positron emission tomography study

Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential focus of neuroinflammation in bipolar disorder. We aim to determine if there is increased [C-11]-(R)-PK11195binding to activated microglia in the hippocampus of patients with bipolar I disorder when compared to healthy controls. Material and methods: Fourteen patients with bipolar I disorder and eleven healthy controls were included in the analyses. Dynamic 60-min PET scans were acquired after the injection of [C-11]-(R)-PK11195. All subjects underwent psychiatric interviews as well as an MRI scan, which was used for anatomic co-registration in the data analysis. The data from the PET scans was analyzed with a twotissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma and blood curve as input. : A significantly increased [C-11]-(R)-PK11195 binding potential, which is indicative of neuroinflammation, was found in the right hippocampus of the patients when compared to the healthy controls (1.66 (CI 1.45-1.91) versus 1.33 (Cl 1.16-1.53); p = 0.033, respectively). Although the same trend was observed in the left hippocampus, this difference was not statistically significant. Conclusion: This study is the first to demonstrate the presence of focal neuroinflammation in the right hippocampus in bipolar I disorder. (C) 2014 Elsevier Inc. All rights reserved

Clinical course long after atrial switch: A novel risk score for major clinical events

BACKGROUND: Patients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival. METHODS AND RESULTS: This multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24–36] years) for 13 (interquartile range, 9–16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%–9%), 23% (95% CI, 17%–28%), and 5% (95% CI, 2%–8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82–0.90]). Observed 5-and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients. CONCLUSIONS: The clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management