ABSTRACT
BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression. OBJECTIVES: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA. METHODS: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677). RESULTS: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001). CONCLUSIONS: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
ABSTRACT
BACKGROUND: Our previous study found degradation to subthalamic neuronal encoding of speech features in Parkinson disease (PD) patients suffering from speech disorders. OBJECTIVE: To find how timing of speech-related neuronal firing changes in PD patients with speech disorders compared to PD patients without speech disorders. METHODS: During the implantation of deep brain stimulator (DBS), we recorded the activity of single neurons in the subthalamic nucleus (STN) of 18 neurosurgical patients with PD while they articulated, listened to, or imagined articulation of 5 vowel sounds, each following a beep. We compared subthalamic activity of PD patients with (n = 10) vs without speech disorders. RESULTS: In this comparison, patients with speech disorders had longer reaction times and shorter lengths of articulation. Their speech-related neuronal activity preceding speech onset (planning) was delayed relative to the beep, but the time between this activity and the emission of speech sound was similar. Notwithstanding, speech-related neuronal activity following the onset of speech (feedback) was delayed when computed relative to the onset. Only in these patients was the time lag of planning neurons significantly correlated with the reaction time. Neuronal activity in patients with speech disorders was delayed during imagined articulation of vowel sounds but earlier during speech perception. CONCLUSION: Our findings indicate that longer reaction times in patients with speech disorders are due to STN or earlier activity of the speech control network. This is a first step in locating the source(s) of PD delays within this network and is therefore of utmost importance for future treatment of speech disorders.
