Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study.

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.

[Clinical features of mental disorders in amyotrophic lateral sclerosis]. / Klinicheskie osobennosti psikhicheskikh narushenii pri bokovom amiotroficheskom skleroze.

OBJECTIVE: To investigate the clinical features of associated mental disorders in amyotrophic lateral sclerosis (ALS). MATERIAL AND METHODS: Twenty-seven patients (9 men and 18 women, mean age 59.8±11.9 years) with the upper and lower motor neuron lesions were studied. The average duration of the disease at the time of examination was 3.2±2.4 years. Clinical psychopathological and follow-up methods were used. The severity of cognitive impairment was measured with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess the severity of depression. RESULTS: Most patients (88.9%) had cognitive impairments. Amnestic disorders were primarily presented by hypo- and dysmnesia. These patients showed slow thinking, torpidity combined with circumstantiality and a tendency to detail. In addition to attentional fluctuations, we observed reduced attentional capacity, higher distractibility, and difficulty concentrating. The later stages of the disease were accompanied by the overall decline of thinking ability and intelligence with severe perseverations, and failure in the adequate self-assessment. More than half of the patients also developed the symptoms, such as dynamic aphasia, as well as functional speech disorders, i.e. gnosis and praxis. The vast majority of the patients had affective disorders (92.3%). So far as the symptoms of the underlying neurological condition worsened, the associated depressive symptoms prevailed (62.9%). Particular attention should be given to the clinical cases of ALS associated with psychotic disorders such as acute schizophrenia-like psychotic disorders. CONCLUSION: Presence of affective, cognitive and behavioral disorders, as well as a specific neuroimaging pattern, are considered as a whole as the manifestation of the behavioral variant of frontotemporal dementia (FTD). This provides support for the current opinion suggesting the similarity of ALS and FTD, which allows for considering these diseases as different phenotypic manifestations of a single pathological process.

[Selecting the optimal treatment for depression taking into account the psychotropic and somatotropic effects of the antidepressant]. / Vybor optimal'noi terapii depressii s uchetom psikhotropnogo i somatotropnogo effektov antidepressanta (klinicheskii sluchai).

Based on a clinical case, the authors consider the problem of the optimal choice of an antidepressant, taking into account not only the psychopathological structure of depression, the severity and characteristics of its triad, but also the presence of somatic symptoms. This determines the need for a comprehensive analysis of the pharmacological profile of prescribed antidepressants, their psychotropic and somatotropic effects. The switch of the patient to brintellix, which has polymodal neuroreceptor activity, at a dose of 20 mg per day, made it possible to achieve remission and reduce adverse reactions caused by SSRIs.