Impact of Prolonged Spaceflight on Orthostatic Tolerance During Ambulation and Blood Pressure Profiles in Astronauts.

BACKGROUND: Astronauts returning to earth usually demonstrate reduced orthostatic tolerance when assessed on a tilt table or quiet standing, but no studies have evaluated postflight orthostatic tolerance during activities of daily living, when it is most clinically relevant. Ambulatory blood pressure (BP) variability also is associated with orthostatic intolerance in certain patient populations and can capture clinically significant orthostatic hypotension during activities of daily living, especially when measured on a beat-to-beat basis. We evaluated the impact of prolonged spaceflight on orthostatic tolerance and BP profiles in astronauts. METHODS: Ambulatory beat-to-beat BP was recorded using a portable device for multiple 24-hour time periods before, during, and after 6 months of spaceflight in 12 astronauts (4 women; age 48±5 [mean±SD] years). BP variability in the time domain was calculated as the SD. Systolic BP distribution during activities of daily living was characterized by skewness and kurtosis. RESULTS: In contrast with results from previous studies that used tilt tables or stand tests, no astronaut experienced orthostatic intolerance/hypotension during activities of daily living before or after spaceflight. Also, 24-hour systolic BP decreased in space (120±10 mm Hg before spaceflight versus 106±9 mm Hg during spaceflight; P<0.01), but it returned to normal upon landing (122±13 mm Hg). Diastolic BP was unchanged during and after spaceflight. Systolic and diastolic BP variability remained the same before, during, and after spaceflight (both P>0.05). The skewness of systolic BP increased in space (0.74±0.51 versus 1.43±1.00; P=0.001), indicating that signal fluctuations became asymmetrical; however, it returned to preflight levels after landing (0.51±0.42). The kurtosis increased in space (5.01±7.67 versus 11.10±11.79; P=0.010), suggesting that fluctuations concentrated around the mean with a narrow distribution; however, it also returned to preflight levels (2.21±2.56) after return to earth. CONCLUSIONS: Given current countermeasures including in-flight exercise training and volume resuscitation on return, no astronauts experienced orthostatic hypotension or intolerance during routine (for landing day) activities in the initial 24 hours after landing following 6 months in space. Prolonged exposure to spaceflight had little impact on systolic BP variability and its distribution, although the latter showed a transient change in space (accompanied by mild relative hypotension), all of which returned to preflight values after return to earth.

Cardiac Effects of Long-Duration Space Flight.

BACKGROUND: Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training. OBJECTIVES: The goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight. METHODS: We measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests. RESULTS: Total cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112). CONCLUSIONS: The current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.

Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction.

BACKGROUND: Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a approximately 5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. METHODS: Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. RESULTS: Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value. CONCLUSION: Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

Effects of Prolonged Spaceflight on Atrial Size, Atrial Electrophysiology, and Risk of Atrial Fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) in active astronauts is ≈5%, similar to the general population but at a younger age. Risk factors for AF include left atrial enlargement, increased number of premature atrial complexes, and certain parameters on signal-averaged electrocardiography, such as P-wave duration, root mean square voltage for the terminal 20 ms of the signal-averaged P wave, and P-wave amplitude. We aimed to evaluate changes in atrial structure, supraventricular beats, and atrial electrophysiology to determine whether spaceflight could increase the risk of AF. METHODS: Thirteen astronauts underwent cardiac magnetic resonance imaging to assess atrial structure and function before and after 6 months in space and high-resolution Holter monitoring for multiple 48-hour time periods before flight, during flight, and on landing day. RESULTS: Left atrial volume transiently increased after 6 months in space (12±18 mL; P=0.03) without changing atrial function. Right atrial size remained unchanged. No changes in supraventricular beats were noted. One astronaut had a large increase in supraventricular ectopic beats but none developed AF. Filtered P-wave duration did not change over time, but root mean square voltage for the terminal 20 ms decreased on all fight days except landing day. No changes in P-wave amplitude were seen in leads II or V1 except landing day for lead V1. CONCLUSIONS: Six months of spaceflight may be sufficient to cause transient changes in left atrial structure and atrial electrophysiology that increase the risk of AF. However, there was no definite evidence of increased supraventricular arrhythmias and no identified episodes of AF.

Effect of Gravitational Gradients on Cardiac Filling and Performance.

BACKGROUND: Gravity affects every aspect of cardiac performance. When gravitational gradients are at their greatest on Earth (i.e., during upright posture), orthostatic intolerance may ensue and is a common clinical problem that appears to be exacerbated by the adaptation to spaceflight. We sought to elucidate the alterations in cardiac performance during preload reduction with progressive upright tilt that are relevant both for space exploration and the upright posture, particularly the preload dependence of various parameters of cardiovascular performance. METHODS: This was a prospective observational study with tilt-induced hydrostatic stress. Echocardiographic images were recorded at four different tilt angles in 13 astronauts, to mimic varying degrees of gravitational stress: 0° (supine, simulating microgravity of space), 22° head-up tilt (0.38 G, simulating Martian gravity), 41° (0.66 G, simulating approximate G load of a planetary lander), and 80° (1 G, effectively full Earth gravity). These images were then analyzed offline to assess the effects of preload reduction on anatomical and functional parameters. RESULTS: Although three-dimensional end-diastolic, end-systolic, and stroke volumes were significantly reduced during tilting, ejection fractions showed no significant change. Mitral annular e' and a' velocities were reduced with increasing gravitational load (P < .001 and P = .001), although s' was not altered. Global longitudinal strain (GLS; from -19.8% ± 2.2% to -14.7% ± 1.5%) and global circumferential strain (GCS; from -29.2% ± 2.5% to -26.0% ± 1.8%) were reduced significantly with increasing gravitational stress (both P < .001), while the change in strain rates were less certain: GLSR (P = .049); GCSR (P = .55). End-systolic elastance was not consistently changed (P = .53), while markers of cardiac afterload rose significantly (effective arterial elastance, P < .001; systemic vascular resistance, P < .001). CONCLUSIONS: Preload modification with gravitational loading alters most hemodynamic and echocardiographic parameters including e' velocity, GLS, and GCS. However, end-systolic elastance and strain rate appear to be more load-independent measures to examine alterations in the cardiovascular function during postural and preload changes, including microgravity.

Real-time 12-lead high-frequency QRS electrocardiography for enhanced detection of myocardial ischemia and coronary artery disease.

Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

Comparison of echocardiographic changes after short- and long-duration spaceflight.

BACKGROUND: Previous echocardiographic studies of astronauts before and after short-duration (4-17 d) missions have demonstrated a decrease in resting left ventricular stroke volume, but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long-duration (129-144 d) spaceflight have been rare and their overall results equivocal. METHODS: Echocardiographic measurements (M-mode, 2-D, and Doppler) were obtained from short-duration (n = 13) and long-duration (n = 4) crewmembers to evaluate cardiac chamber sizes and function. RESULTS: Compared with short-duration astronauts, long-duration crewmembers had decreases in EF (+6+/-0.02 vs. -10.5+/-0.03%, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07%, p = 0.015), and an increase in left ventricular end systolic volume (-12+/-0.06 vs. +39+/-0.24%, p = 0.011). CONCLUSIONS: These data suggest a reduction in cardiac function that relates to mission duration. As the changes in BP and circulating blood volume are reported to be similar after short- and long-duration flights, the smaller EF after longer spaceflights may be due to a decrease in cardiac function rather than altered blood volume.

The mystery of sudden death: mechanisms for risks.

This review addresses the possible overlapping mechanisms that may apply to the risk of sudden unexpected death occurring in epilepsy and in cardiac disease. It explores the interaction between the central and peripheral autonomic nervous systems and the cardiopulmonary systems. Included is a discussion of the potential interactive role of genetically determined subtle cardiac risk factors for arrhythmias with a predisposition for seizure-related cardiac arrhythmias. We address the possible mechanisms that are operant in producing both epileptogenic and cardiogenic arrhythmias. Finally, we speculate about potential preventive measures to minimize the risk of both sudden unexpected death in epilepsy and sudden cardiac death.