Getting to an ImprOved Understanding of Low-Density Lipoprotein-Cholesterol and Dyslipidemia Management (GOULD): Methods and baseline data of a registry of high cardiovascular risk patients in the United States.

BACKGROUND: Guidelines for managing patients with atherosclerotic cardiovascular disease (ASCVD) recommend statin therapy initially. Target levels/goals for low-density lipoprotein-cholesterol (LDL-C) were initially included, subsequently de-emphasized in 2013, and then re-introduced as thresholds, leading to confusion in clinical practice. We designed a multicenter, observational registry of patients with ASCVD, to describe and track LDL-C treatment patterns in the United States over time. METHODS: Patients with ASCVD receiving any pharmacologic lipid-lowering therapy were eligible for enrollment in one of three cohorts: 1) currently receiving a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), or not receiving PCSK9i with 2) LDL-C 70-99 mg/dL, or 3) LDL-C ≥100 mg/dL. Patients undergo a 1-year retrospective chart review, followed by chart reviews and phone interviews every 6 months for 2 years. RESULTS: A total of 5006 patients were enrolled at 119 centers. Mean age was 68 years, 40% of patients were female, 86% were white, 80% had coronary artery disease, and 33% had type 2 diabetes mellitus. Among those not on a PCSK9i, high-intensity statins and ezetimibe were utilized in only 44% and 9%, respectively. Among women vs men, only 36.6% vs 48.2% received high-intensity statins (P < .001). Among patients on a PCSK9i, only one-third were receiving a statin, suggesting statin intolerance is a driver of PCSK9i use at present. CONCLUSION: Our data on current practice in the US continue to illustrate that high-intensity statins and ezetimibe are underutilized in at-risk patients outside of clinical trials, particularly women. This study will track temporal changes in treatment patterns and identify opportunities for improvement in lipid management in patients with ASCVD.

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

OBJECTIVE: Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. MATERIALS AND METHODS: The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. RESULTS: Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. CONCLUSION: This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization.

Use of a Cardiac Scale to Predict Heart Failure Events: Design of SCALE-HF 1.

BACKGROUND: There is a need for simple, noninvasive solutions to remotely monitor and predict worsening heart failure (HF) events. SCALE-HF 1 (Surveillance and Alert-Based Multiparameter Monitoring to Reduce Worsening Heart Failure Events) is a prospective, multicenter study that will develop and assess the accuracy of the heart function index-a composite algorithm of noninvasive hemodynamic biomarkers from a cardiac scale-in predicting worsening HF events. METHODS: Approximately 300 patients with chronic HF and recent decompensation will be enrolled in this observational study for model development. Patients will be encouraged to take daily cardiac scale measurements. RESULTS: Approximately 50 HF events, defined as an urgent, unscheduled clinic, emergency department, or hospitalization for worsening HF will be used for model development. The composite index will be developed from hemodynamic biomarkers derived from ECG, ballistocardiogram, and impedance plethysmogram signals measured from the cardiac scale. Biomarkers of interest include weight, peripheral impedance, pulse rate and variability, and estimates of stroke volume, cardiac output, and blood pressure captured through the cardiac scale. The sensitivity, unexplained alert rate, and alerting time of the index in predicting worsening HF events will be evaluated and compared with the performance of simple weight-based rule-of-thumb algorithms (eg, weight increase of 3 lbs in 1 day or 5 lbs in 7 days) that are often used in practice. CONCLUSIONS: SCALE-HF 1 is the first study to develop and evaluate the performance of a composite index derived from noninvasive hemodynamic biomarkers measured from a cardiac scale in predicting worsening HF events. Subsequent studies will validate the heart function index and assess its ability to improve patient outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04882449.

Noninvasive Scale Measurement of Stroke Volume and Cardiac Output Compared With the Direct Fick Method: A Feasibility Study.

Background Objective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions. We assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient's feet while standing on the scale, in measuring stroke volume and cardiac output compared with the gold-standard direct Fick method. Methods and Results Thirty-two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test. Stroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r=0.81 and r=0.85, respectively (P<0.001 each). The mean absolute error of the scale estimated stroke volume was -1.58 mL, with a 95% limits of agreement of -21.97 to 18.81 mL. The mean error for the scale estimated cardiac output was -0.31 L/min, with a 95% limits of agreement of -2.62 to 2.00 L/min. The changes in stroke volume and cardiac output before and after exercise were 78.9% and 96.7% concordant, respectively, between the 2 measuring methods. Conclusions In a proof-of-concept study, this novel scale with cardiac monitoring abilities may allow for noninvasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient's lifestyle.

Lateralization of the Subthalamic Nucleus with Age in Parkinson's Disease.

Age-related changes in subthalamic nucleus (STN) position have not been well characterized in patients with Parkinson's disease (PD). We report a systematic retrospective analysis of age-related changes in radiographic and final deep brain stimulator (DBS) STN coordinates in PD patients. The charts of 134 PD patients (97 males, 28-84 years) representing 255 STN were reviewed. Multiple linear regression, stepwise regression, and relative importance of regressors analysis was performed to determine the significance of the relationship between STN position and age. Across all subjects, both radiographic STN localization and final DBS position within the STN showed a lateralization of the STN target with age (R2=0.1096,p=6.9×10-8 and R2=0.0433,p=8.7×10-4, respectively). Lateralization with age was observed regardless of MR field strength (1.5T and 3.0T) (R2=0.0946,p=7.6×10-6 and R2=0.2687,p=9.2×10-5, respectively). No other consistent or clinically significant age-related changes were identified. Multiple linear regression revealed that the third ventricle width and age are statistically significant predictors of radiographic STN lateralization (R2 = 0.2404, p = 1.51×10-5 and p = .00784 respectively). Step-wise regression demonstrated that age is a non-redundant predictor of STN lateralization relative to third ventricle width. Similar to healthy controls, STN position appears to shift laterally with age in PD. This highlights limitations of indirect targeting and atlas-based stereotactic surgery and argues for reliance on patient specific anatomy since factors such as age and 3rd ventricular width can contribute to patient-specific variability in STN localization.

Inhibition of return in a visual foraging task in non-human subjects.

Inhibition of return is thought to help guide visual search by inhibiting the orienting of attention to previously attended locations. We have previously shown that, in a foraging visual search task, the neural responses to objects in parietal cortex are reduced after they have been examined. Here we ask whether the animals' reaction times (RTs) in the same task show a psychophysical correlate of inhibition of return: a slowing of reaction time in response to a probe placed at a previously fixated location. We trained three animals to perform an RT version of the visual foraging task. In the foraging task, subjects visually searched through an array of five identical distractors and five identical potential targets; one of which had a reward linked to it. In the RT variant of the task, subjects had to rapidly respond to a probe if it appeared. We found that RTs were slower for probes presented at locations that contained previously fixated objects, faster to potential targets and between the two for behaviorally irrelevant distractors that had not been fixated. These data show behavioral inhibitory tagging of previously fixated objects and suggest that the suppression of activity seen previously in the same task in parietal cortex could be a neural correlate of this mechanism.