Right Ventricular and Pulmonary Computed Tomography Assessments in Paradoxical Low-Flow Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background: Patients with paradoxical low-flow low-gradient aortic stenosis (pLFLG-AS) have high mortality and high degree of TAVR futility. Computed tomography (CT) enables accurate simultaneous right ventricular (RV) and parenchymal lung disease evaluation which may provide useful objective markers of AS severity, concomitant pulmonary comorbidities, and transcatheter aortic valve replacement (TAVR) improvement. However, the prevalence of RV dysfunction and its association with pulmonary disease in pLFLG-AS is unknown. The study objective was to test the hypothesis that pLFLG-AS patients undergoing TAVR have decreased RV function without significant parenchymal lung disease. Methods: Between August 2016 and March 2020, 194 consecutive AS patients completed high-resolution computed tomography (CT) imaging for TAVR evaluation. Subjects were stratified based on echocardiographic criteria as the study group, pLFLG (n=27), and two consecutive control groups: classic severe, normal-flow, high-gradient (n=27) and normal-flow, low-gradient (NFLG) (n=27) AS. Blinded biventricular function and lung parenchymal disease assessments were obtained by high-resolution CT imaging. Results: Patient demographics were similar between groups. pLFLG-AS had lower RV ejection fraction (49±10%) compared to both classic severe (58±7%, p<0.001) and NFLG AS (55±65%, p=0.02). There were no significant differences on lung emphysema (p=0.19), air fraction (p=0.58), and pulmonary disease presence (p=0.94) and severity (p=0.67) between groups. Conclusion: pLFLG-AS patients have lower RV ejection fraction, than classic severe and normal-flow low-gradient AS patients in the absence of significant parenchymal lung disease on CT imaging. These findings support the direct importance of RV function in the pathophysiology of aortic valve disease.

Safety and Feasibility of a Novel, Second-Generation Robotic-Assisted System for Percutaneous Coronary Intervention: First-in-Human Report.

OBJECTIVES: The goal of this study is to evaluate the safety and efficacy of the second-generation robotic-assisted system CorPath GRX (Corindus) for percutaneous coronary intervention (PCI). BACKGROUND: The first-generation CorPath 200 robotic-assisted system for PCI is effective, but is limited by the lack of an active robotic guide-catheter control. The CorPath GRX device enables robotic guide-catheter manipulation, in addition to guidewire and balloon/stent delivery. However, there have been no clinical data reported with this device. METHODS: Consecutive patients with demonstrated obstructive coronary artery disease (>70% stenosis) and clinical indications for PCI were treated with the CorPath GRX system and enrolled in the study. The two co-primary endpoints were clinical procedural success (final TIMI 3 flow, and <30% residual stenosis without in-hospital major adverse cardiac event) and device technical success (robotic clinical procedural success without the need for unplanned manual assistance/conversion). RESULTS: The study enrolled 40 subjects (65.7 ± 11.9 years; 72.5% males; 54 lesions) with a high proportion of American College of Cardiology/American Heart Association type B2/C lesions (77.8%). Clinical procedural success and device technical success rates were 97.5% (n = 39 of 40) and 90.0% (n = 36 of 40), respectively. CONCLUSION: The second-generation CorPath GRX system for robotic-assisted PCI is safe and effective, and achieves high rates of clinical and technical success in a cohort of patients with complex coronary disease.

Association of Blood Pressure Trajectory With Mortality, Incident Cardiovascular Disease, and Heart Failure in the Cardiovascular Health Study.

BACKGROUND: Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain. METHODS: We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models. RESULTS: Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy. CONCLUSIONS: Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.

No association of cryptococcal antigenemia with poor outcomes among antiretroviral therapy-experienced HIV-infected patients in Addis Ababa, Ethiopia.

INTRODUCTION: There are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. We assessed clinical outcomes of a predominantly asymptomatic, ART-experienced cohort of HIV+ patients previously found to have a high (8.4%) prevalence of cryptococcal antigenemia. METHODS: The study took place at All Africa Leprosy, Tuberculosis and Rehabilitative Training Centre and Black Lion Hospital HIV Clinics in Addis Ababa, Ethiopia. A retrospective study design was used to perform 12-month follow-up of 367 mostly asymptomatic HIV-infected patients (CD4<200 cells/µl) with high levels of antiretroviral therapy use (74%) who were previously screened for cryptococcal antigenemia. Medical chart abstraction was performed approximately one year after initial screening to obtain data on clinic visit history, ART use, CD4 count, opportunistic infections, and patient outcome. We evaluated the association of cryptococcal antigenemia and a composite poor outcome of death and loss to follow-up using logistic regression. RESULTS: Overall, 323 (88%) patients were alive, 8 (2%) dead, and 36 (10%) lost to follow-up. Among the 31 patients with a positive cryptococcal antigen test (titers ≥1∶8) at baseline, 28 were alive (all titers ≤1∶512), 1 dead and 2 lost to follow-up (titers ≥1∶1024). In multivariate analysis, cryptococcal antigenemia was not predictive of a poor outcome (aOR = 1.3, 95% CI 0.3-4.8). A baseline CD4 count <100 cells/µl was associated with an increased risk of a poor outcome (aOR 3.0, 95% CI 1.4-6.7) while an increasing CD4 count (aOR 0.1, 95% CI 0.1-0.3) and receiving antiretroviral therapy at last follow-up visit (aOR 0.1, 95% CI 0.02-0.2) were associated with a reduced risk of a poor outcome. CONCLUSIONS: Unlike prior ART-naïve cohorts, we found that among persons receiving ART and with CD4 counts <200 cells/µl, asymptomatic cryptococcal antigenemia was not predictive of a poor outcome.

High prevalence of Cryptococcal antigenemia among HIV-infected patients receiving antiretroviral therapy in Ethiopia.

BACKGROUND: Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia. METHODS: Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤ 200 cells/µl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia. RESULTS: 369 HIV-infected patients were enrolled; mean CD4 123 cells/µl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/µl, 8.9% with CD4 100 to 150 cells/µl and 5.7% with CD4150-200 cell/µl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/µl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia. CONCLUSION: Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.

The effect of electrical and mechanical stimulation on the regenerating rodent facial nerve.

OBJECTIVES/HYPOTHESIS: Investigators have long sought realistic methods to accelerate regeneration following nerve injury. Herein, we investigated the degree to which manual target muscle manipulation and brief electrical stimulation of the facial nerve, alone or in combination, affects recovery following rat facial nerve injury. STUDY DESIGN: Prospective, randomized animal study. METHODS: Sixty rats were randomized to three groups: brief electrical stimulation (BES), mechanical stimulation of the whisker pad (MEC), or both (COMBO). Animals underwent facial nerve transection and immediate microsurgical repair. In BES and COMBO groups, transection was preceded by 1-hour (3 V, 20 Hz square wave) electrical stimulation. Animals were tested weekly, with 5-minute recording sessions of whisker movement. In the MEC and COMBO groups, animals received 5 minutes of daily massage to the left whisker pad throughout the recovery period. Whisking behavior was analyzed for comparisons. RESULTS: The BES and MEC groups demonstrated improved functional recovery in all whisking parameters compared with the COMBO group or historical controls at most time points between postoperative weeks 1 and 7. After 12 weeks, functional recovery remained superior in the BES and MEC groups compared with the COMBO and control groups, although the effect was no longer statistically significant. CONCLUSIONS: We observed an accelerative recovery effect of either electrical nerve stimulation or massage of the whisker pad on whisking behavior. The combination of both interventions had a negating effect on the acceleration of recovery. The potential clinical utility of these modalities bears consideration, and their negating interaction warrants further study.

Daily facial stimulation to improve recovery after facial nerve repair in rats.

OBJECTIVE: To establish whether daily mechanical stimulation improves functional recovery of whisking after facial nerve transection injury and repair in rats. METHODS: Forty rats underwent facial nerve transection injury and repair and subsequent quantitative facial movement testing. Animals were randomized into 2 experimental groups (n = 20 each). Both groups received daily 5-minute manual stimulation of their whiskers, with one group undergoing whisker protraction and the other, whisker retraction. Rats were tested on postoperative weeks 1, 4 through 8, and 15 via a validated, quantitative whisking kinematics apparatus. Whisks were counted and analyzed for whisking amplitude, velocity, and acceleration. RESULTS: Animals receiving manual stimulation by passive protraction of their whiskers demonstrated significantly improved functional recovery at multiple time points during the 15 weeks compared with historical controls (P < .005; 1-tailed t test). Recovery was similar in the protraction and retraction groups, trending toward better whisking recovery in the protraction group. CONCLUSIONS: Daily mechanical whisker stimulation via either protraction or retraction significantly improves recovery of whisking after facial nerve transection and repair. This finding supports the role of early soft-tissue manipulation after facial nerve repair and may have clinical implications for the postoperative management of patients after facial nerve manipulations.

Nimodipine and acceleration of functional recovery of the facial nerve after crush injury.

OBJECTIVE: To establish whether nimodipine, a calcium channel blocker, accelerates or otherwise improves functional recovery of whisking after facial nerve crush injury in the rat. METHODS: Thirty rats underwent exposure of the left main trunk of the facial nerve followed by a standard crush injury and subsequent quantitative facial movement testing. Animals were randomized into an experimental group (n = 15) and a control group (n = 15). Four days prior to facial nerve manipulation, experimental animals underwent subcutaneous implantation of a nimodipine-secreting pellet. All animals were tested preoperatively and on postoperative days 2, 8 to 17, 20, 22, 24, and 31 using a validated, quantitative whisking kinematics apparatus. Whisks were analyzed for amplitude, velocity, and acceleration. RESULTS: Animals receiving nimodipine demonstrated significantly better whisking on 5 days (postoperative days 9, 11 to 13, and 20) compared with control animals (P < .001, P = .003, P = .009, P = .009, and P = .009, respectively; 1-tailed ttest). Overall, the nimodipine-treated animals showed earlier recovery compared with the untreated animals. CONCLUSIONS: We demonstrate that nimodipine improves recovery of whisking after facial nerve crush. This finding corroborates the semiquantitative findings of others, and provides complete whisking kinematic data on its effects. Given the low adverse effect profile of nimodipine, there may be clinical implications in its administration in patients experiencing facial nerve injury.

Evidence for facial nerve-independent mechanisms of blinking in the rat.

PURPOSE: The rat facial nerve (CN VII) controls the orbicularis oculi (OO) muscle, which contracts to close the palpebral fissure during blinking. It was recently observed that rats are able to achieve nearly complete eye closure shortly after CN VII lesion, and hypothesized that the retractor bulbi (RB) muscle assumes an important compensatory role after CN VII lesion. This study was undertaken to determine the maintenance of rat corneal health and eye closure capability after lesion of the OO, RB, or both. METHODS: Twenty-two rats underwent RB transection; 12 of them had undergone complete unilateral CN VII transection (OO denervation) 15 weeks earlier. Corneal appearance and ability to blink in response to a corneal air puff was monitored weekly for 9 weeks. An additional 13 rats received CN VII transection and were video recorded (1000 frames/s) during elicited blinks at days 1, 3, 5/6, and 11 after surgery. RESULTS: Rats achieved nearly full or full eye closure after OO paralysis or RB myotomy, respectively. Ninety-two percent of rats maintained good corneal health after OO denervation over 9 weeks, consistent with compensatory eyelid movement served by the RB muscles. In contrast, only 40% of rats with loss of RB function alone and only 17% of rats with concurrent OO and RB paralysis were able to maintain corneal health by week 3. CONCLUSIONS: Like other small mammals, the rat RB musculature can support nearly complete eye closure when CN VII is lesioned, and must be carefully considered when using blink as a functional recovery parameter of facial nerve lesion.