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.

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.

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.

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.

Feasibility and safety of exercise stress testing using an anti-gravity treadmill with Tc-99m tetrofosmin single-photon emission computed tomography (SPECT) myocardial perfusion imaging: A pilot non-randomized controlled study.

BACKGROUND: Exercise is the AHA/ACC guideline-recommended stress modality for myocardial perfusion imaging, but many patients are unable to exercise to target heart rate on a conventional treadmill. We examined the feasibility and safety of stress imaging using an anti-gravity treadmill in patients with perceived poor exercise capacity. METHODS AND RESULTS: 49 patients were recruited for stress testing by anti-gravity treadmill (n = 29) or to a regadenoson control group (n = 20). Seventeen anti-gravity test patients (59%) reached target heart rate obviating the need for a pharmacologic stress agent. Adverse effects of the anti-gravity treadmill were limited to minor muscle aches in 5 subjects. Stress myocardial perfusion image quality judged by 3 blinded readers on a 5-point scale was comparable for the anti-gravity treadmill (4.30 ± SD 0.87) vs pharmacologic stress (4.28 ± SD 0.66). CONCLUSION: Stress testing using an anti-gravity treadmill is feasible and may help some patients safely achieve target heart rate.

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.

Cardiac autonomic innervation.

The autonomic nervous system plays a key role in regulating changes in the cardiovascular system and its adaptation to various human body functions. The sympathetic arm of the autonomic nervous system is associated with the fight and flight response, while the parasympathetic division is responsible for the restorative effects on heart rate, blood pressure, and contractility. Disorders involving these two divisions can lead to, and are seen as, a manifestation of most common cardiovascular disorders. Over the last few decades, extensive research has been performed establishing imaging techniques to quantify the autonomic dysfunction associated with various cardiovascular disorders. Additionally, several techniques have been tested with variable success in modulating the cardiac autonomic nervous system as treatment for these disorders. In this review, we summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors. We have also discussed several imaging modalities available to aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques, including pharmacologic and device-based therapies, that have been or are being tested currently.

Computer derived transient ischemic dilation ratio for identifying extensive coronary artery disease using a CZT camera and imaging in the upright position.

BACKGROUND: Transient ischemic dilation (TID) of the left ventricle (LV) has not been validated as a marker of extensive coronary artery disease (CAD) for studies using a cadmium-zinc-telluride (CZT) camera with upright imaging. METHODS: TID ratios were obtained from upright stress and rest images on a CZT camera. Separate cut-off values were determined for exercise and for regadenoson stress. The cutoffs were then applied to 28 patients with extensive CAD and 101 patients without extensive CAD. RESULTS: With treadmill exercise, an upright TID ratio ≥1.16 provided a positive predictive value of 50% and a negative predictive value of 85.4% for the identification of extensive CAD. In the regadenoson group, an upright TID ratio of 1.29 provided a positive predictive value of 20% and a negative predictive value of 75.9%. Although not an independent predictor of extensive CAD in all subjects, in subjects with a normal upright LVEF, it provided a predictive value by receiver operating characteristics comparable to the SSS. CONCLUSIONS: Increased upright TID measurements on a CZT camera are associated with extensive CAD. The upright TID measurements can serve in an adjunctive role to SSS, and may be most effective in patients with a normal upright exercise LVEF.

Predicting Heart Rate at the Ventilatory Threshold for Aerobic Exercise Prescription in Persons With Chronic Stroke.

BACKGROUND AND PURPOSE: Treadmill aerobic exercise improves gait, aerobic capacity, and cardiovascular health after stroke, but a lack of specificity in current guidelines could lead to underdosing or overdosing of aerobic intensity. The ventilatory threshold (VT) has been recommended as an optimal, specific starting point for continuous aerobic exercise. However, VT measurement is not available in clinical stroke settings. Therefore, the purpose of this study was to identify an accurate method to predict heart rate at the VT (HRVT) for use as a surrogate for VT. METHODS: A cross-sectional design was employed. Using symptom-limited graded exercise test (GXT) data from 17 subjects more than 6 months poststroke, prediction methods for HRVT were derived by traditional target HR calculations (percentage of HRpeak achieved during GXT, percentage of peak HR reserve [HRRpeak], percentage of age-predicted maximal HR, and percentage of age-predicted maximal HR reserve) and by regression analysis. The validity of the prediction methods was then tested among 8 additional subjects. RESULTS: All prediction methods were validated by the second sample, so data were pooled to calculate refined prediction equations. HRVT was accurately predicted by 80% HRpeak (R, 0.62; standard deviation of error [SDerror], 7 bpm), 62% HRRpeak (R, 0.66; SDerror, 7 bpm), and regression models that included HRpeak (R, 0.62-0.75; SDerror, 5-6 bpm). DISCUSSION AND CONCLUSIONS: Derived regression equations, 80% HRpeak and 62% HRRpeak, provide a specific target intensity for initial aerobic exercise prescription that should minimize underdosing and overdosing for persons with chronic stroke. The specificity of these methods may lead to more efficient and effective treatment for poststroke deconditioning.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A114).

Significance of I-123 metaiodobenzylguanidine (¹²³I-MIBG) lung activity in subjects with heart failure in comparison to healthy control subjects.

BACKGROUND: Little is known concerning the significance of lung activity of the sympathetic neuronal imaging agent (123)I-MIBG in heart failure patients and healthy subjects. METHODS: (123)I-MIBG activity was assessed in lung, heart, and mediastinum regions of interest on early and late planar images in 951 heart failure patients and 94 controls. Cox regression analyses were performed to identify factors associated with outcome events during a median 17 month follow-up. RESULTS: Heart failure subjects with pulmonary disease had significantly reduced late lung-to-mediastinum (L/M) ratios compared to heart failure subjects without pulmonary disease. Late L/M ratio was greater in heart failure subjects without outcome events than either subjects with events or healthy controls. L/M ratio was an independent predictor of all-cause mortality. Subjects with combined favorable prognosis L/M ratio ≥ 1.7 and heart-to-mediastinum ratio (H/M) ≥ 1.6 had a significantly lower 2-year mortality (2.0%) than subjects with unfavorable L/M ratio < 1.7 and H/M ratio < 1.6 (17.7% 2-year mortality, P < .0008). CONCLUSIONS: Increased (123)I-MIBG lung activity in heart failure subjects, compared to controls, is associated with a relatively low risk of adverse events, including all-cause mortality. L/M ratio may, therefore, be useful to provide incremental prognostic information on (123)I-MIBG imaging.

High-intensity interval training in stroke rehabilitation.

After stroke, people with weakness enter a vicious cycle of limited activity and deconditioning that limits functional recovery and exacerbates cardiovascular risk factors. Conventional aerobic exercise improves aerobic capacity, function, and overall cardiometabolic health after stroke. Recently, a new exercise strategy has shown greater effectiveness than conventional aerobic exercise for improving aerobic capacity and other outcomes among healthy adults and people with heart disease. This strategy, called high-intensity interval training (HIT), uses bursts of concentrated effort alternated with recovery periods to maximize exercise intensity. Three poststroke HIT studies have shown preliminary effectiveness for improving functional recovery. However, these studies were varied in approach and the safety of poststroke HIT has received little attention. The objectives of this narrative review are to (1) propose a framework for categorizing HIT protocols; (2) summarize the safety and effectiveness evidence of HIT among healthy adults and people with heart disease and stroke; (3) discuss theoretical mechanisms, protocol selection, and safety considerations for poststroke HIT; and (4) provide directions for future research.

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.

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.