Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

A 3-minute recumbent stepper test in chronic stroke.

BACKGROUND: Persons with stroke often have difficulty achieving target heart rate (HR) during graded exercise testing (GXT), which is known to limit test sensitivity for detecting clinically relevant cardiac conditions. A novel Recumbent Stepper 3-minute (RS 3Min) "all out" test may increase sensitivity of stress testing after stroke. OBJECTIVE: To determine the feasibility of adding the RS 3Min test after GXT among persons after stroke. DESIGN: A within-participant, nonrandomized, repeated measures design. SETTING: Rehabilitation research laboratory and cardiovascular stress laboratory PARTICIPANTS: Fifteen participants with chronic stroke (56.7 ± 9.6 years; 6.4 ± 4.3 years post stroke; 8 male). INTERVENTIONS: All participants randomly completed (1) a symptom-limited treadmill GXT and (2) a symptom-limited RS GXT followed by RS 3Min critical power test. MAIN OUTCOME MEASURES: HR, ratings of perceived exertion, oxygen consumption, respiratory exchange ratio, and power output measured continuously during each test. Blood pressure measured every 2 minutes and or immediately post exercise. P value set at p < .05 from omnibus test for a significant difference among protocols. RESULTS: The RS 3Min test had a significantly higher rate of achieving target HR compared to the RS GXT (9/14 vs 4/14, p = .02) and was not significantly different from the treadmill GXT (9/14 vs 5/14, p = .09). Minimum power output during the RS 3Min was significantly higher than peak power output during the RS GXT (110 ± 41 W vs. 84 ± 22 W, p = .02) with 12/15 participants reaching a VO2 plateau. CONCLUSIONS: Although additional studies with randomized designs are needed, a novel RS 3Min "all out" test appears to be a promising method for enhancing test sensitivity in cardiovascular screening after stroke, while providing a potentially valid measure of critical power.

Ventricular Tachycardia or Fibrillation Storm in Coronavirus Disease.

Ventricular tachycardia (VT) or ventricular fibrillation (VF) storm associated with severe acute respiratory syndrome coronavirus 2 infection is a potentially fatal complication; the correlation of these 2 disorders, however, has not been well studied. This retrospective case series examined outcomes of 2 patients who were admitted for repeated implantable cardioverter-defibrillator shocks with or without syncope and observed to have VT/VF storms with COVID-19. Mechanisms of VT/VF storms in COVID-19 are multifactorial including myocarditis, systemic inflammation, hyperadrenergic state, hemodynamic instability, hypoxia, acidosis, and proarrhythmic drugs. A higher incidence of VT/VF storm is observed in patients with comorbidities and those requiring critical care, with some studies reporting increased mortality. In our cohort, 1 of the 2 patients succumbed to the complications from COVID-19, and the other patient was discharged to home in stable condition. Monitoring of life-threatening arrhythmias in the setting of COVID-19 may need to be adopted to prevent morbidity and mortality.

Visual patterns of breast attenuation artifacts in women and men with an upright and supine cadmiun-zinc-telluride camera.

BACKGROUND: Breast attenuation artifacts occurring with upright cadmium-zinc-telluride (CZT) cardiac imaging systems have not been well characterized. METHODS: 216 consecutive patients with Single Photon Emission Computerized Tomography myocardial perfusion imaging and no angiographically significant obstructive coronary artery disease were identified. All upright and supine SPECT images as well as coronary angiograms were reviewed and analyzed in blinded fashion. RESULTS: In women imaged upright, more visual false positive defects were noted in the inferior wall compared to the anterior wall (26 vs. 10 at rest, p = 0.006, and 33 vs. 13 at stress, p < 0.001). Visual inferior wall defects were more common in the upright than supine position at stress (33 vs. 23, p = 0.018) and rest (26 vs. 14, p = 0.011), and most apparent in non-obese women (13 vs. 8, at stress, p = 0.059 and 11 vs. 5, at rest, p = 0.014). CONCLUSIONS: With upright CZT myocardial perfusion imaging, women often have visible inferior wall attenuation artifact defects, likely from pendant breast tissue. These inferior wall attenuation artifacts may be seen in non-obese female patients.

Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension.

BACKGROUND: The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH). METHODS: We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes. RESULTS: Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001). CONCLUSIONS: These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.

Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial.

BACKGROUND: Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training. METHODS: Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40-80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training. DISCUSSION: This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03760016 . Registered on November 30, 2018.

Effects of gender and defect reversibility on detection of coronary disease with an upright and supine cadmium-zinc-telluride camera.

BACKGROUND: Limited data address the roles of gender, perfusion defect reversibility, and imaging position in interpretation of images acquired on an upright/supine cadmium-zinc-telluride (CZT) cardiac imaging system. METHODS AND RESULTS: From a consecutive cohort of patients imaged on an upright/supine CZT camera, 260 patients with coronary angiograms were studied. Multivariable models identified gender as a significant effect modifier for imaging variables of CAD. For males, a supine summed stress score (SSS) ≥ 3 provided high accuracy (sensitivity 70.7%, specificity 72.2%), and highest contribution to multivariable models. In females, supine SSS ≥ 2 provided the best cut-off for defect size and severity (sensitivity 90%, specificity 35.9%), but specificity was improved substantially to 53.3% with decrease in sensitivity to 80% by also requiring quantitative identification of perfusion defect reversibility in the supine position. Eight variables, accurate for predicting coronary disease, were more accurate with supine than upright imaging. CONCLUSIONS: Perfusion defect reversibility improved specificity in female patients for detection of coronary disease compared to perfusion defect size and extent alone. Supine images provided superior accuracy for detection of coronary disease compared to upright images.

Locomotor training intensity after stroke: Effects of interval type and mode.

Background and Objectives: High-intensity interval training (HIIT) is a promising strategy for improving gait and fitness after stroke, but optimal parameters remain unknown. We tested the effects of short vs long interval type and over-ground vs treadmill mode on training intensity. Methods: Using a repeated measures design, 10 participants with chronic hemiparesis performed 12 HIIT sessions over 4 weeks, alternating between short and long-interval HIIT sessions. Both protocols included 10 minutes of over-ground HIIT, 20 minutes of treadmill HIIT and another 10 minutes over-ground. Short-interval HIIT involved 30 second bursts at maximum safe speed and 30-60 second rest periods. Long-interval HIIT involved 4-minute bursts at ~90% of peak heart rate (HRpeak) and 3-minute recovery periods at ~70% HRpeak. Results: Compared with long-interval HIIT, short-interval HIIT had significantly faster mean overground speeds (0.75 vs 0.67 m/s) and treadmill speeds (0.90 vs 0.51 m/s), with similar mean treadmill HR (82.9 vs 81.8%HRpeak) and session perceived exertion (16.3 vs 16.3), but lower overground HR (78.4 vs 81.1%HRpeak) and session step counts (1481 vs 1672). For short-interval HIIT, training speeds and HR were significantly higher on the treadmill vs. overground. For long-interval HIIT, the treadmill elicited HR similar to overground training at significantly slower speeds. Conclusions: Both short and long-interval HIIT elicit high intensities but emphasize different dosing parameters. From these preliminary findings and previous studies, we hypothesize that overground and treadmill short-interval HIIT could be optimal for improving gait speed and overground long-interval HIIT could be optimal for improving gait endurance.

Effects of Exercise Intensity on Acute Circulating Molecular Responses Poststroke.

Background. Exercise intensity can influence functional recovery after stroke, but the mechanisms remain poorly understood. Objective. In chronic stroke, an intensity-dependent increase in circulating brain-derived neurotrophic factor (BDNF) was previously found during vigorous exercise. Using the same serum samples, this study tested acute effects of exercise intensity on other circulating molecules related to neuroplasticity, including vascular-endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), and cortisol, with some updated analyses involving BDNF. Methods. Using a repeated-measures design, 16 participants with chronic stroke performed 3 exercise protocols in random order: treadmill high-intensity interval training (HIT-treadmill), seated-stepper HIT (HIT-stepper), and treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum molecular changes were compared between protocols. Mediation and effect modification analyses were also performed. Results. VEGF significantly increased during HIT-treadmill, IGF1 increased during both HIT protocols and cortisol nonsignificantly decreased during each protocol. VEGF response was significantly greater for HIT-treadmill versus MCT-treadmill when controlling for baseline. Blood lactate positively mediated the effect of HIT on BDNF and cortisol. Peak treadmill speed positively mediated effects on BDNF and VEGF. Participants with comfortable gait speed ≥0.4 m/s had significantly lower VEGF and higher IGF1 responses, with a lower cortisol response during MCT-treadmill. Conclusions. BDNF and VEGF are promising serum molecules to include in future studies testing intensity-dependent mechanisms of exercise on neurologic recovery. Fast training speed and anaerobic intensity appear to be critical ingredients for eliciting these molecular responses. Serum molecular response differences between gait speed subgroups provide a possible biologic basis for previously observed differences in training responsiveness.

Enterococcus faecalis Endocarditis After Endoscopic Mucosal Resection of a Large Sessile Colonic Polyp.

A 71-year-old man with mitral regurgitation and apical cardiomyopathy underwent endoscopic mucosal resection of a 22-mm transverse colon tubulovillous adenoma with high-grade dysplasia. Six weeks later, he presented with fever, valvular vegetations, and positive blood cultures for Enterococcus faecalis. To our knowledge, this is the first reported case of endocarditis involving native heart valves after endoscopic mucosal resection.

Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter test-retest reproducibility study.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test-retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test-retest difference was 0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

Exercise intensity affects acute neurotrophic and neurophysiological responses poststroke.

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

Analysis of stress-only imaging, comparing upright and supine CZT camera acquisition to conventional gamma camera images with and without attenuation correction, with coronary angiography as a reference.

BACKGROUND: Diagnostic performance of stress-only imaging using a Cadmium-Zinc-Telluride (CZT) camera has not been directly compared in the same patients to stress-only attenuation-corrected conventional Anger camera images. METHODS: 112 subjects with correlative coronary angiographic data and 40 subjects with <5% pre-test likelihood of coronary disease completed attenuation-corrected stress-only images on a conventional Anger camera and uncorrected upright and supine stress images on a CZT camera. Two readers provided independent, blinded interpretations of stress-only images. RESULTS: Upright and supine stress-only CZT images and attenuation-corrected Anger camera images provided similar positive (reader 1/reader 2, 50.0%/44.1% vs 46.4%/51.9%) and negative (66.7%/64.0% vs 67.9%/67.7%) predictive values (all P = NS) for obstructive coronary artery disease; however, the sensitivity was higher (81.3% vs 58.3%, P = .05), specificity lower (29.7% vs 50.0%, P = .005), and normalcy rate lower (87.5% vs 100%, P = .025) with attenuation-corrected Anger camera images for the first reader with no significant differences between cameras for the second reader. CONCLUSIONS: Stress-only upright and supine CZT imaging was non-inferior statistically to attenuation-corrected stress-only Anger camera imaging. Nevertheless, stress-only CZT imaging may be associated with reduced diagnostic sensitivity for some readers compared to attenuation-corrected Anger camera images, which may be less acceptable clinically compared to stress plus rest images.

Sympathetic drive stimulating diastolic dysfunction?

Diastolic heart failure accounts for half of the heart failure population and its pathophysiology remains an area of active research. The renin angiotensin and aldosterone axis has been the focus of clinical trials to treat patients with heart failure with preserved ejection fraction, however with limited yield in terms of clinical success. Sympathetic activity has been considered a plausible cause for the molecular changes that lead to diastolic dysfunction. Based on this understanding the study by Gimelli et al uses MIBG to evaluate for association between diastolic dysfunction and sympathetic denervation. The results of this study set the stage for a follow up study for evaluation of sympathetic denervation in isolated diastolic dysfunction.