Anemia in Cardiovascular Disease: Marker of Disease Severity or Disease-modifying Therapeutic Target?

PURPOSE OF THE REVIEW: In this review paper, we examine the latest evidence regarding the use of iron supplementation, erythropoiesis-stimulating agents (ESAs), and blood transfusions as therapeutic targets for anemia to mitigate morbidity and mortality in patients with cardiovascular disease. RECENT FINDINGS: Intravenous ferric carboxymaltose (FC) injections in heart failure (HF) have resulted in improved self-reported patient symptoms; higher exercise capacity, as measured by 6-min walk test distance in anemic patients; and lower re-hospitalization rates in iron deficient patients. Darbepoetin alfa has shown evidence of improved Kansas City Cardiomyopathy Questionnaire scores. No mortality benefits have been noted thus far with FC injections or darbepoetin in HF, with an increase in adverse events with darbepoetin. Aggressive transfusions (Hg < 10 g/dL) are not associated with improved outcomes in cardiovascular disease. Quality of life metrics, rather than mortality, appear to improve with IV FC and ESA use in HF. More studies are required to see if these treatments have a role in coronary artery disease. Current evidence suggests that anemia is a marker of underlying disease severity, with a limited role in disease modification. Further studies are required to solidify our understanding of this topic.

Racial Differences in Heart Age and Impact on Mortality.

BACKGROUND: Heart age is an estimate of the age of a person's cardiovascular system given their cardiovascular disease (CVD) risk factors. The difference between a person's chronological age and heart age (excess heart age) represents their added CVD risk. OBJECTIVE: To examine racial differences in excess heart age and whether race impacts the association between excess heart age and CVD mortality. METHODS: This analysis included 5110 participants (2449 non-Hispanic white, 1287 non-Hispanic black, and 1374 Mexican-American) from the NHANES III who were free of CVD. Heart age was calculated using the sex-specific non-laboratory-based Framingham risk prediction functions. Multivariable Cox proportional-hazards regression models were used to evaluate the relationship (overall and by race) between excess heart age and CVD mortality. RESULTS: Mean excess heart age was greatest in non-Hispanic blacks (13.0 years), followed by Mexican-Americans (10.5 years), and non-Hispanic whites (8.5 years); p < 0.001 for pairwise differences. Over a mean follow-up of 13.0 years, 394 CVD deaths occurred. Each 10 years of excess heart age was associated with 65% increased risk of CVD mortality (HR, 95% CI: 1.65, 1.53-1.78). This association was stronger in non-Hispanic whites (1.83, 1.63-2.02) compared to non-Hispanic blacks (1.50, 1.29-1.72) and Mexican American (1.60, 1.33-1.87), interaction p = 0.065. CONCLUSIONS: Compared to non-Hispanic whites, non-Hispanic blacks and Mexican Americans have more excess heart age, but the risk of CVD death for the same level of excess heart age appears more pronounced in non-Hispanic whites. Further investigation is needed to show the usefulness of these findings in directing future efforts and resource allocation for reduction of health disparities between ethnic groups.

Clinical, hemispheric, and autonomic changes associated with use of closed-loop, allostatic neurotechnology by a case series of individuals with self-reported symptoms of post-traumatic stress.

BACKGROUND: The objective of this pilot study was to explore the use of a closed-loop, allostatic, acoustic stimulation neurotechnology for individuals with self-reported symptoms of post-traumatic stress, as a potential means to impact symptomatology, temporal lobe high frequency asymmetry, heart rate variability (HRV), and baroreflex sensitivity (BRS). METHODS: From a cohort of individuals participating in a naturalistic study to evaluate use of allostatic neurotechnology for diverse clinical conditions, a subset was identified who reported high scores on the Posttraumatic Stress Disorder Checklist (PCL). The intervention entailed a series of sessions wherein brain electrical activity was monitored noninvasively at high spectral resolutions, with software algorithms translating selected brain frequencies into acoustic stimuli (audible tones) that were delivered back to the user in real time, to support auto-calibration of neural oscillations. Participants completed symptom inventories before and after the intervention, and a subset underwent short-term blood pressure recordings for HRV and BRS. Changes in temporal lobe high frequency asymmetry were analyzed from baseline assessment through the first four sessions, and for the last four sessions. RESULTS: Nineteen individuals (mean age 47, 11 women) were enrolled, and the majority also reported symptom scores that exceeded inventory thresholds for depression. They undertook a median of 16 sessions over 16.5 days, and 18 completed the number of sessions recommended. After the intervention, 89% of the completers reported clinically significant decreases in post-traumatic stress symptoms, indicated by a change of at least 10 points on the PCL. At a group level, individuals with either rightward (n = 7) or leftward (n = 7) dominant baseline asymmetry in temporal lobe high frequency (23-36 Hz) activity demonstrated statistically significant reductions in their asymmetry scores over the course of their first four sessions. For 12 individuals who underwent short-term blood pressure recordings, there were statistically significant increases in HRV in the time domain and BRS (Sequence Up). There were no adverse events. CONCLUSION: Closed-loop, allostatic neurotechnology for auto-calibration of neural oscillations appears promising as an innovative therapeutic strategy for individuals with symptoms of post-traumatic stress. TRIALS REGISTRATION: ClinicalTrials.gov #NCT02709369 , retrospectively registered on March 4, 2016.

Stealing from the Heart: A Rare Case of Chest Pain Post-Coronary Artery Bypass Grafting.

A 70-year-old veteran with prior triple vessel coronary artery bypass grafting (CABG) presented with exertional chest pain. His work-up revealed > 40 mm Hg bilateral upper extremity blood pressure difference. Chest computed tomography and invasive angiography revealed severe stenosis at the ostium of the left subclavian artery, proximal to the origin of the left internal mammary artery to left anterior descending artery graft (LIMA-LAD). A diagnosis of coronary subclavian steal syndrome (CSSS) was made, and carotid-subclavian bypass was performed. This case outlines when to suspect CSSS, an approach to its diagnosis, and the importance of its timely management.

Heart Block in Unpalliated Complex Adult Congenital Heart Disease: Massive Collateral Burden Precludes Epicardial Pacemaker.

Complete heart block is a common complication for adults with congenital heart disease (CHD). Epicardial pacing is preferred in patients with septal shunting due to risk of thromboembolism. Anatomic changes in complex CHD may preclude surgical epicardial lead placement. Thromboembolism risk reduction in such patients requiring endocardial pacing remains questionable. (Level of Difficulty: Advanced.).

Improvements in Heart Rate Variability, Baroreflex Sensitivity, and Sleep After Use of Closed-Loop Allostatic Neurotechnology by a Heterogeneous Cohort.

BACKGROUND: Heart rate variability (HRV) is an indicator of dynamic adaptability of the autonomic nervous system. Few interventions target upstream, cerebral cortex components of the heart-brain system for autonomic management. We report changes in HRV and baroreflex sensitivity (BRS), associated with use of a noninvasive, closed-loop, allostatic, computer-guided, acoustic stimulation neurotechnology. METHODS: Over 5 years, 220 subjects with heterogeneous neurological, cardiovascular, and psychophysiological conditions consecutively enrolled in a naturalistic, single-arm study exploring clinical effects associated with use of the neurotechnology. Of those, 202 completed the study protocol and 160 had recordings adequate to analyze HRV and BRS. Mean age was 44.0 (SD 19.4), with 130 women. Participants received a mean of 16.1 (5.2) sessions, over 24.2 days (23.3), with 9.5 (3.8) actual intervention days. Sessions included real-time analysis of brain electrical activity and software algorithm-guided translation of selected frequencies into patterns of acoustic stimulation (audible tones of variable pitch and timing), to facilitate auto-calibration of neural oscillations. Outcomes including 10-min supine, at-rest recordings of blood pressure and heart rate, and inventories for insomnia (ISI) and depression (CES-D or BDI-II), were obtained at baseline and 15.3 (16.7) days after the last session. RESULTS: Compared to baseline, significant increases (all p < 0.001) were observed for measures of HRV across all participants including the mean percentage change for SDNN 24.2% (SE 0.04), and RMSSD, 42.2% (0.08), and BRS [Sequence Up, 55.5% (0.09), Sequence Down, 77.6% (0.23), and Sequence All, 53.7% (0.07)]. Significant improvements were noted in SAP, MAP, and DAP, as well as natural log of HF, and total power. Self-reported ISI was reduced (ISI, -6.4 points, SD 5.6, p < 0.001). The proportion reporting clinically significant depressive symptoms reduced from 48.2% at baseline to 22.1% at follow-up. Linear regression showed that rightward asymmetry predicted lower SDNN (p = 0.02). Exploratory analysis showed a trend for improved balance of temporal lobe high-frequency amplitudes over the course of initial sessions. CONCLUSION: These findings indicate that use of a noninvasive, allostatic, closed-loop neurotechnology appears to have robust potential for public health efforts to support greater flexibility in autonomic cardiovascular regulation, through self-optimization of electrical activity at the level of the brain.

Using Accelerometer and Gyroscopic Measures to Quantify Postural Stability.

CONTEXT: Force platforms and 3-dimensional motion-capture systems provide an accurate method of quantifying postural stability. Substantial cost, space, time to administer, and need for trained personnel limit widespread use of biomechanical techniques in the assessment of postural stability in clinical or field environments. OBJECTIVE: To determine whether accelerometer and gyroscope data sampled from a consumer electronics device (iPad2) provide sufficient resolution of center-of-gravity (COG) movements to accurately quantify postural stability in healthy young people. DESIGN: Controlled laboratory study. SETTING: Research laboratory in an academic medical center. PATIENTS OR OTHER PARTICIPANTS: A total of 49 healthy individuals (age = 19.5 ± 3.1 years, height = 167.7 ± 13.2 cm, mass = 68.5 ± 17.5 kg). INTERVENTION(S): Participants completed the NeuroCom Sensory Organization Test (SOT) with an iPad2 affixed at the sacral level. MAIN OUTCOME MEASURE(S): Primary outcomes were equilibrium scores from both systems and the time series of the angular displacement of the anteroposterior COG sway during each trial. A Bland-Altman assessment for agreement was used to compare equilibrium scores produced by the NeuroCom and iPad2 devices. Limits of agreement was defined as the mean bias (NeuroCom - iPad) ± 2 standard deviations. Mean absolute percentage error and median difference between the NeuroCom and iPad2 measurements were used to evaluate how closely the real-time COG sway measured by the 2 systems tracked each other. RESULTS: The limits between the 2 devices ranged from -0.5° to 0.5° in SOT condition 1 to -2.9° to 1.3° in SOT condition 5. The largest absolute value of the measurement error within the 95% confidence intervals for all conditions was 2.9°. The mean absolute percentage error analysis indicated that the iPad2 tracked NeuroCom COG with an average error ranging from 5.87% to 10.42% of the NeuroCom measurement across SOT conditions. CONCLUSIONS: The iPad2 hardware provided data of sufficient precision and accuracy to quantify postural stability. Accuracy, portability, and affordability make using the iPad2 a reasonable approach for assessing postural stability in clinical and field environments.

Asymmetrical pedaling patterns in Parkinson's disease patients.

BACKGROUND: Approximately 1.5 million Americans are affected by Parkinson's disease (Deponti et al., 2013) which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. METHODS: Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 W, 60 W, maximum performance). FINDINGS: Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 W and 60 W stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. INTERPRETATION: This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and future lower extremity function.