Selectively diminished corpus callosum fibers in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS), a condition associated with mutations in the PHOX2B gene, is characterized by loss of breathing drive during sleep, insensitivity to CO2 and O2, and multiple somatomotor, autonomic, neuropsychological, and ophthalmologic deficits, including impaired intrinsic and extrinsic eye muscle control. Brain structural studies show injury in peri-callosal regions and the corpus callosum (CC), which has the potential to affect functions disturbed in the syndrome; however, the extent of CC injury in CCHS is unclear. Diffusion tensor imaging (DTI)-based fiber tractography procedures display fiber directional information and allow quantification of fiber integrity. We performed DTI in 13 CCHS children (age, 18.2±4.7 years; eight male) and 31 control (17.4±4.9 years; 18 male) subjects using a 3.0-Tesla magnetic resonance imaging scanner; CC fibers were assessed globally and regionally with tractography procedures, and fiber counts and densities compared between groups using analysis-of-covariance (covariates; age and sex). Global CC evaluation showed reduced fiber counts and densities in CCHS over control subjects (CCHS vs. controls; fiber-counts, 4490±854 vs. 5232±777, P<0.001; fiber-density, 10.0±1.5 vs. 10.8±0.9 fibers/mm2, P<0.020), and regional examination revealed that these changes are localized to callosal axons projecting to prefrontal (217±47 vs. 248±32, P<0.005), premotor (201±51 vs. 241±47, P<0.012), parietal (179±64 vs. 238±54, P<0.002), and occipital regions (363±46 vs. 431±82, P<0.004). Corpus callosum fibers in CCHS are compromised in motor, cognitive, speech, and ophthalmologic regulatory areas. The mechanisms of fiber injury are unclear, but may result from hypoxia or perfusion deficits accompanying the syndrome, or from consequences of PHOX2B action.

Central autonomic regulation in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show significant autonomic dysfunction in addition to the well-described loss of breathing drive during sleep. Some characteristics, for example, syncope, may stem from delayed sympathetic outflow to the vasculature; other symptoms, including profuse sweating, may derive from overall enhanced sympathetic output. The dysregulation suggests significant alterations to autonomic regulatory brain areas. Murine models of the genetic mutations present in the human CCHS condition indicate brainstem autonomic nuclei are targeted; however, the broad range of symptoms suggests more widespread alterations. We used functional magnetic resonance imaging (fMRI) to assess neural response patterns to the Valsalva maneuver, an autonomic challenge eliciting a sequence of sympathetic and parasympathetic actions, in nine CCHS and 25 control subjects. CCHS patients showed diminished and time-lagged heart rate responses to the Valsalva maneuver, and muted fMRI signal responses across multiple brain areas. During the positive pressure phase of the Valsalva maneuver, CCHS responses were muted, but were less so in recovery phases. In rostral structures, including the amygdala and hippocampus, the normal declining patterns were replaced by increasing trends or more modest declines. Earlier onset responses appeared in the hypothalamus, midbrain, raphé pallidus, and left rostral ventrolateral medulla. Phase-lagged responses appeared in cerebellar pyramis and anterior cingulate cortex. The time-distorted and muted central responses to autonomic challenges likely underlie the exaggerated sympathetic action and autonomic dyscontrol in CCHS, impairing cerebral autoregulation, possibly exacerbating neural injury, and enhancing the potential for cardiac arrhythmia.

Reduced caudate nuclei volumes in patients with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) children show cognitive and affective deficits, in addition to state-specific loss of respiratory drive. The caudate nuclei serve motor, cognitive, and affective roles, and show structural deficits in CCHS patients, based on gross voxel-based analytic procedures. However, the magnitude and regional sites of caudate injury in CCHS are unclear. We assessed global caudate nuclei volumes with manual volumetric procedures, and regional volume differences with three-dimensional surface morphometry in 14 CCHS (mean age+/-SD: 15.1+/-2.3 years; 8 male) and 31 control children (15.1+/-2.4 years; 17 male) using brain magnetic resonance imaging (MRI). Two high-resolution T1-weighted image series were collected using a 3.0 Tesla MRI scanner; images were averaged and reoriented (rigid-body transformation) to common space. Both left and right caudate nuclei were outlined in the reoriented images, and global volumes calculated; surface models were derived from manually-outlined caudate structures. Global caudate nuclei volume differences between groups were evaluated using a multivariate analysis of covariance (covariates: age, gender, and total intracranial volume). Both left and right caudate nuclei volumes were significantly reduced in CCHS over control subjects (left, 4293.45+/-549.05 vs. 4626.87+/-593.41 mm(3), P<0.006; right, 4376.29+/-565.42 vs. 4747.81+/-578.13 mm(3), P<0.004). Regional deficits in CCHS caudate volume appeared bilaterally, in the rostral head, ventrolateral mid, and caudal body. Damaged caudate nuclei may contribute to CCHS neuropsychological and motor deficits; hypoxic processes, or maldevelopment in the condition may underlie the injury.

Hypercapnic exposure in congenital central hypoventilation syndrome reveals CNS respiratory control mechanisms.

Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses and loss of breathlessness to hypercapnia, yet arouse from sleep to high CO2, suggesting intact chemoreceptor afferents. The syndrome provides a means to differentiate brain areas controlling aspects of breathing. We used functional magnetic resonance imaging to determine brain structures responding to inspired 5% CO2-95% O2 in 14 CCHS patients and 14 controls. Global signal changes induced by the challenge were removed on a voxel-by-voxel basis. A priori-defined volume-of-interest time trends (assessed with repeated measures ANOVA) and cluster analysis based on modeling each subject to a step function (individual model parameter estimates evaluated with t-test, corrected for multiple comparisons) revealed three large response clusters to hypercapnia distinguishing the two groups, extending from the 1) posterior thalamus through the medial midbrain to the dorsolateral pons, 2) right caudate nucleus, ventrolaterally through the putamen and ventral insula to the mid-hippocampus, and 3) deep cerebellar nuclei to the dorsolateral cerebellar cortex bilaterally. Smaller clusters and defined areas of group signal differences in the midline dorsal medulla, amygdala bilaterally, right dorsal-posterior temporal cortex, and left anterior insula also emerged. In most sites, early transient or sustained responses developed in controls, with little, or inverse change in CCHS subjects. Limbic and medullary structures regulating responses to hypercapnia differed from those previously shown to mediate loaded breathing ventilatory response processing. The findings show the significant roles of cerebellar and basal ganglia sites in responding to hypercapnia and the thalamic and midbrain participation in breathing control.

Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show deficient respiratory and cardiac responses to hypoxia and hypercapnia, despite apparently intact arousal responses to hypercapnia and adequate respiratory motor mechanisms, thus providing a model to evaluate functioning of particular brain mechanisms underlying breathing. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals, corrected for global signal changes, and evaluated them with cluster and volume-of-interest procedures, during a baseline and 2-min hypoxic (15% O(2), 85% N(2)) challenge in 14 CCHS and 14 age- and gender-matched control subjects. Hypoxia elicited significant (P < 0.05) differences in magnitude and timing of responses between groups in cerebellar cortex and deep nuclei, posterior thalamic structures, limbic areas (including the insula, amygdala, ventral anterior thalamus, and right hippocampus), dorsal and ventral midbrain, caudate, claustrum, and putamen. Deficient responses to hypoxia included no, or late, changes in CCHS patients with declining signals in control subjects, a falling signal in CCHS patients with no change in controls, or absent early transient responses in CCHS. Hypoxia resulted in signal declines but no group differences in hypothalamic and dorsal medullary areas, the latter being a target for PHOX2B, mutations of which occur in the syndrome. The findings extend previously identified posterior thalamic, midbrain, and cerebellar roles for normal mediation of hypoxia found in animal fetal and adult preparations and suggest significant participation of limbic structures in responding to hypoxic challenges, which likely include cardiovascular and air-hunger components. Failing structures in CCHS include areas additional to those associated with PHOX2B expression and chemoreceptor sites.

fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses to CO2 and hypoxia and reduced drive to breathe during sleep but retain appropriate breathing patterns in response to volition or increased exercise. Breath-by-breath influences on heart rate are also deficient. Using functional magnetic resonance imaging techniques, we examined responses over the brain to voluntary forced expiratory loading, a task that CCHS patients can perform but that results in impaired rapid heart rate variation patterns normally associated with the loading challenge. Increased signals emerged in control (n = 14) over CCHS (n = 13; ventilator dependent during sleep but not waking) subjects in the cingulate and right parietal cortex, cerebellar cortex and fastigial nucleus, and basal ganglia, whereas anterior cerebellar cortical sites and deep nuclei, dorsal midbrain, and dorsal pons showed increased signals in the patient group. The dorsal and ventral medulla showed delayed responses in CCHS patients. Primary motor and sensory areas bordering the central sulcus showed comparable responses in both groups. The delayed responses in medullary sensory and output regions and the aberrant reactions in cerebellar and pontine sensorimotor coordination areas suggest that rapid cardiorespiratory integration deficits in CCHS may stem from defects in these sites. Additional autonomic and perceptual motor deficits may derive from cingulate and parietal cortex aberrations.

Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by diminished upper airway muscle phasic and tonic activation during sleep, but enhanced activity during waking. We evaluated neural mechanisms underlying these patterns with functional magnetic resonance imaging procedures during baseline and expiratory loading conditions in nine medication-free OSA and 16 control subjects. Both groups developed similar expiratory loading pressures, but appropriate autonomic responses did not emerge in OSA cases. Reduced neural signals emerged in OSA cases within the frontal cortex, anterior cingulate, cerebellar dentate nucleus, dorsal pons, anterior insula and lentiform nuclei. Signal increases in OSA over control subjects developed in the dorsal midbrain, hippocampus, quadrangular cerebellar lobule, ventral midbrain and ventral pons. Fastigial nuclei and the amygdala showed substantially increased variability in OSA subjects. No group differences were found in the thalamus. OSA patients show aberrant responses in multiple brain areas and inappropriate cardiovascular responses to expiratory loading, perhaps as a consequence of previously-demonstrated limbic, cerebellar and motor area gray matter loss.

The relationship between obesity and mortality in patients with heart failure.

OBJECTIVES: The study aimed to evaluate the role of obesity in the prognosis of patients with heart failure (HF). BACKGROUND: Previous reports link obesity to the development of HF. However, the impact of obesity in patients with established HF has not been studied. METHODS: We analyzed 1,203 patients with advanced HF followed in a comprehensive HF management program. The patients were subclassified into categories of body mass index (BMI) defined as: underweight BMI <20.7 (n = 164), recommended BMI 20.7 to 27.7 (n = 692), overweight BMI 27.8 to 31 (n = 168) and obese BMI >31 (n = 179). This sample size allows the detection of small effects (0.02), with a power of 0.80 and an alpha level of 0.05 for comparing one-year survival between BMI groups. RESULTS: The four BMI groups had similar profiles in terms of ejection fraction (mean 0.22), sodium, creatinine and smoking. The obese and overweight groups had significantly higher rates of hypertension and diabetes, as well as higher levels of cholesterol, triglycerides and low density lipoprotein cholesterol. The four BMI groups had similar survival rates. Ejection fraction, HF etiology and angiotensin-converting enzyme inhibitor use predicted survival on univariate analysis (p < 0.01), although BMI did not. On multivariate analysis, cardiopulmonary exercise tests, pulmonary capillary wedge pressure and serum sodium were strong predictors of survival (p < 0.05). Higher BMI was not a risk factor for increased mortality, but was associated with a trend toward improved survival. CONCLUSIONS: In a large cohort of patients with advanced HF of multiple etiologies, obesity is not associated with increased mortality and may confer a more favorable prognosis. Further studies need to delineate whether weight loss promotion in medically optimized patients with HF is a worthwhile therapeutic goal.

Predictors of isotonic exercise in patients with heart failure.

PURPOSE: Study aims were to determine the predictors of isotonic resistance exercise performance in patients with advanced heart failure and to compare the preexercise values of patients who experienced a negative physiologic response to resistance exercise with those who had minimal or no response. METHODS: A correlational design was used. After pharmacologic left ventricular unloading therapy using a pulmonary artery catheter, 34 patients with advanced heart failure performed graduated isotonic weight-lifting exercises. Measurements were made of hemodynamics and rating of perceived exertion after each test. RESULTS: The following variables, measured at baseline, were significantly correlated with the amount of weight patients were able to lift: rating of perceived exertion (RPE; r = -0.42, P = 0.014); diastolic blood pressure (DBP; r = 0.49, P = 0.03); systolic blood pressure (SBP; r = 0.40, P = 0.017); pulmonary capillary wedge pressure (PCWP; r = 0.39, P = 0.026); and right atrial pressure (RAP; r = 0.35, P = 0.041). Multiple regression analysis, using a stepwise procedure, showed that 47% of the variance in exercise performance was explained by DBP, RPE, and PCWP. There were no significant differences in baseline hemodynamics, ejection fraction, or age between the group of patients who had a negative hemodynamic response at peak exercise and the group of patients who had minimal or no response. CONCLUSIONS: Resting PCWP, DBP, and RPE can provide important information to help clinicians predict isotonic resistance exercise performance in patients with advanced heart failure. However, those patients who have a negative response to this type of exercise cannot be distinguished at baseline by clinical characteristics or age.

The hemodynamic effects of isotonic exercise using hand-held weights in patients with heart failure.

BACKGROUND: Controversy surrounds the use of resistance exercise in patients with heart failure because of concerns that increases in rate-pressure product and systemic vascular resistance might lead to increased afterload and decreased cardiac output. METHODS: Following pharmacologic left ventricular unloading therapy using a pulmonary artery catheter, 34 patients with advanced heart failure performed isotonic weightlifting exercise at 50%, 65%, and 80% of the calculated one repetition maximum. Measurements were made of hemodynamics, ST segment, rate-pressure product, serum norepinephrine, rating of perceived exertion, and dysrhythmias following each exercise set. RESULTS: Repeated analysis of variance showed significant increases in systolic blood pressure (p = 0.0005), diastolic blood pressure (p = 0.01), rate-pressure product (p = 0.005); serum norepinephrine (p = 0.004), and rating of perceived exertion (p = 0.0005). However, systemic vascular resistance and cardiac output did not change significantly (p>0.05). Pulmonary capillary wedge pressures, the incidence of dysrhythmias, and ST segments did not significantly differ from baseline. No patients experienced angina or dyspnea during the study. CONCLUSIONS: Isotonic exercise using hand-held weights was well tolerated hemodynamically and clinically, and no patients experienced adverse outcomes during exercise.

Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure.

BACKGROUND: This study determined whether evidence of congestion after 4 to 6 weeks of heart failure management predicted outcome for patients hospitalized with chronic New York Heart Association class IV symptoms. Class IV symptoms predict high mortality rates, but outcome is not known for patients who improve to establish freedom from congestion. Revised estimates at 1 month could facilitate decisions regarding transplantation and other high-risk interventions. METHODS: At 4 to 6 weeks after hospital discharge, 146 patients were evaluated for congestion by 5 criteria (orthopnea, jugular venous distention, edema, weight gain, and new increase in baseline diuretics). Heart failure management included inpatient therapy tailored to relieve congestion, followed by adjustments to maintain fluid balance during the next 4 weeks. RESULTS: Freedom from congestion was demonstrated at 4 to 6 weeks in 80 (54%) patients, who had 87% subsequent 2-year survival compared with 67% in 40 patients with 1 or 2 criteria of congestion and 41% in 26 patients with 3 to 5 criteria. The Cox proportional hazards model identified left ventricular dimension, pulmonary wedge pressure on therapy, and freedom from congestion as independent predictors of survival. Persistence of orthopnea itself predicted 38% 2-year survival (without urgent transplantation) versus 77% in 113 without orthopnea. Serum sodium was lower and blood urea nitrogen and heart rate higher when orthopnea persisted. CONCLUSIONS: The ability to maintain freedom from congestion identifies a population with good survival despite previous class IV symptoms. At 4 to 6 weeks, patients with persistent congestion may be considered for high-risk intervention.

Visualization of sleep influences on cerebellar and brainstem cardiac and respiratory control mechanisms.

Cerebellar and vestibular structures exert substantial influences on breathing and cardiovascular activity, particularly under conditions of extreme challenges. Influences from these structures, as well as from the ventral medullary surface, are greatly modified during sleep states. Vestibular lesions abolish the pronounced phasic autonomic variation found in the rapid eye movement sleep state, and spontaneous ventral medullary surface activity, as assessed by optical procedures, is greatly diminished in that state. Neural responses from the ventral medullary surface to hypotensive challenges are enhanced and appear "undampened" during the rapid eye movement sleep state. Functional magnetic resonance imaging reveals activation to blood pressure challenges in widespread brain areas of humans, and especially in cerebellar sites, such as the fastigial nucleus. A subset of victims of sudden infant death syndrome, a sleep-related disorder, appear to succumb from cardiovascular failure of a shock-like nature, and often show neurotransmitter receptor deficiencies in the ventral medullary surface, caudal midline raphe hypotensive regions, and the inferior olive, a major afferent relay to the cerebellum. Afferent and efferent vestibular/cerebellar structures, or sites within the cerebellum may mediate failure mechanisms in sudden infant death syndrome and a number of other sleep-disordered breathing and cardiovascular syndromes.

Comparison of Internet versus lecture instructional methods for teaching nursing research.

Although many higher education programs are using the Internet to teach classes, there are few published reports on the effectiveness of this method on test scores or student satisfaction. The purpose of this study was to compare test and student satisfaction scores of graduate nursing students who take a nursing research course via the Internet with those of students who take the same course via traditional lecture instruction. In addition, student technical support use and Internet student lecture attendance also were examined. A total of 97 students (Internet, 44; lectures, 53) participated. There were no significant differences in test scores and overall course student satisfaction (P > .05). However, the Internet students reported significantly higher (P = .04) stimulation of learning compared with the traditional lecture students. Technical support use by the Internet students was high initially and was related to software problems. Of interest were the large proportion of Internet students (73 percent) who attended at least 3 of the 10 lectures. Use of the Internet to teach graduate-level nursing research can provide comparable learning and student satisfaction to traditional lecture instructional methods.

Improved survival in patients with nonischemic advanced heart failure and syncope treated with an implantable cardioverter-defibrillator.

The purpose of this study was to assess whether in patients with syncope and heart failure due to nonischemic cardiomyopathy, treatment with an implantable cardioverter-defibrillator (ICD) compared with conventional medical therapy is associated with a reduction in sudden death and total mortality. Patients with advanced heart failure who have syncope have been shown to be at high risk for sudden death. Further risk stratification has been difficult in patients with nonischemic cardiomyopathy in whom inducibility on electrophysiologic study is not predictive of future risk. Of 639 consecutive patients with nonischemic cardiomyopathy referred for heart transplantation, 147 patients with history of syncope and no prior history of sustained ventricular tachycardia or cardiac arrest were identified. Outcomes were compared for the 25 patients managed with an ICD and 122 patients managed with conventional medical therapy. There were no differences in the baseline variables in the 2 groups of patients, including age, ejection fraction, and medical treatments for heart failure, but patients receiving an ICD were more likely to have had nonsustained ventricular tachycardia (56% vs. 15%, p = 0.001). During a mean follow-up of 22 months, there were 31 deaths, 18 sudden, in patients treated with conventional therapy, whereas there were 2 deaths, none sudden, in patients treated with an ICD. An appropriate shock occurred in 40% of the ICD patients. Actuarial survival at 2 years was 84.9% with ICD therapy and 66.9% with conventional therapy (p = 0.04). Thus, in patients with nonischemic cardiomyopathy and syncope, therapy with an ICD is associated with a reduction in sudden death and an improvement in overall survival.

Acquisition of electrophysiologic signals during magnetic resonance imaging.

We describe a low cost system for acquiring electrophysiological signals during magnetic resonance imaging. The system consists of high common-mode-rejection and low noise operational amplifiers, coupled by fiber optic cables to a receiver located at the periphery of the magnetic field. The system minimizes noise introduction which would contaminate image signals.

Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

Skin tests to recall antigens are performed as indicators of clinical outcomes in heart failure (HF). A diminution in the response to recall antigens, termed "anergy," is regarded as an indication of poorer clinical prognosis, although little analysis has been done to support that conclusion. Patients with advanced HF (n=222) in New York Heart Association classes III and IV, with complete datasets for all of the variables, were studied. The sample was 77% men, mean age 52+/-12 years, and left ventricular ejection fraction, 21+/-7. Patients with ischemic (n=113) and idiopathic (n=109) disease were analyzed separately. The relation of anergy to 1-year mortality and selected hemodynamic factors, blood chemistries, medications, and nutritional status markers was analyzed. Anergy was present in 45% (47% idiopathic and 42% ischemic) of patients. Anergy was related to 1-year mortality (univariate p=0.038) in patients with ischemic, but not idiopathic, HF. Anergic patients with ischemic HF had shorter survival times (p=0.035). Lower cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were predictors (p <0.001) of mortality in idiopathic HF. In ischemic HF, lower cholesterol, LDL, and triglycerides were univariate predictors (p <0.001, p=0.004, and p=0.005, respectively) of skin test anergy, but not mortality. Thus, there were distinct differences in clinical correlates of skin test anergy in patients with idiopathic and ischemic HF. This study supports evaluation of anergy to skin tests as one of the markers of mortality in patients with ischemic HF.

Impact of a comprehensive heart failure management program on hospital readmission and functional status of patients with advanced heart failure.

OBJECTIVES: To assess the impact of a comprehensive heart failure management program, functional status, hospital readmission rate and estimated hospital costs were determined and compared for the 6 months before and the 6 months after referral. BACKGROUND: The course of advanced heart failure is characterized by progressive clinical deterioration reflected in frequent hospital admissions, which comprise the major financial cost. METHODS: Over a 3-year period, 214 patients were accepted for heart transplantation and discharged after evaluation, which included adjustments in medical therapy and intensive patient education. Patients were in New York Heart Association functional class III or IV (94 and 120 patients, respectively), with a mean left ventricular ejection fraction of 0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital admissions in the previous 6 months (average 2.0 per patient). Changes in the medical regimen included a 98% increase in angiotensin-converting enzyme inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with counseling also regarding diet and progressive exercise. RESULTS: During the 6 months after referral, there were only 63 hospital readmissions (85% reduction), with 0.29/patient (p < 0.0001). Functional status improved as assessed by functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg per min, p < 0.001). The same results were seen after excluding the 35 patients without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during hospital readmission, 12 elective transplant procedures from home); 34 hospital admissions occurred after referral, compared with 344 before referral. Even when adding in the initial hospital admission after referral for these 179 patients, there was a 35% decrease in total hospital admissions in the 6-month period. The estimated savings in hospital readmission costs after subtracting the initial hospital costs for management was $9,800 per patient. CONCLUSIONS: Comprehensive heart failure management led to improved functional status and an 85% decrease in the hospital admission rate for transplant candidates discharged after evaluation. The potential to reduce both symptoms and costs suggests that referral to a heart failure program may be appropriate not only for potential heart transplantation, but also for medical management of persistent functional class III and IV heart failure.

Six-minute walk test and heart rate variability: lack of association in advanced stages of heart failure.

BACKGROUND: The 6-minute walk and heart rate variability have been used to assess mortality risk in patients with heart failure, but their relationship to each other and their usefulness for predicting mortality at 1 year are unknown. OBJECTIVE: To assess the relationships between the 6-minute walk test, heart rate variability, and 1-year mortality. METHOD: A sample of 113 patients in advanced stages of heart failure (New York Heart Association Functional Class III-IV, left ventricular ejection < 0.25) were studied. All 6-minute walks took place in an enclosed, level, measured corridor and were supervised by the same nurse. Heart rate variability was measured by using (1) a standard-deviation method and (2) Poincaré plots. Data on RR intervals obtained by using 24-hour Holter monitoring were analyzed. Survival was determined at 1 year after the Holter recording. RESULTS: The results showed no significant associations between the results of the 6-minute walk and the two measures of heart rate variability. The results of the walk were related to 1-year mortality but not to the risk of sudden death. Both measures of heart rate variability had significant associations with 1-year mortality and with sudden death. However, only heart rate variability measured by using Poincaré plots was a predictor of total mortality and risk of sudden death, independent of left ventricular ejection fraction, serum levels of sodium, results of the 6-minute walk test, and the standard-deviation measure of heart rate variability. CONCLUSIONS: Results of the 6-minute walk have poor association with mortality and the two measures of heart rate variability in patients with advanced-stage heart failure and a low ejection fraction. Further studies are needed to determine the optimal clinical usefulness of the 6-minute walk and heart rate variability in patients with advanced-stage heart failure.

Predictors of natural killer cell-mediated cytotoxicity deficiency in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

The effect of psychologic variables (situational emotional state and psychiatric diagnosis) and physiologic variables (plasma norepinephrine, decreased cardiac exercise capacity, and elevated pulmonary capillary wedge pressure) on natural killer cell activity was evaluated in 19 patients with advanced heart failure of ischemic or idiopathic origin. Only peak exercise capacity was independently predictive of natural killer cell deficiency.

Voluntary control of vascular tone by using skin-temperature biofeedback-relaxation in patients with advanced heart failure.

BACKGROUND: Advanced heart failure is characterized by activation of the sympathetic nervous system and intense vasoconstriction. Biofeedback-relaxation techniques have been used successfully to treat conditions with similar pathophysiological features. OBJECTIVES: The purpose of this study was to determine if conscious control of skin temperature via a biofeedback-relaxation technique could produce vasodilation and alter central hemodynamic status and circulating levels of catecholamines in patients with heart failure. METHODS: Forty patients with advanced heart failure were randomly assigned to either an intervention or a control group. The study was done in a special cardiac step-down unit accepting patients for hemodynamic monitoring. The patients in the intervention group had one session of skin-temperature biofeedback augmented by imagery of hand warmth and modified progressive muscle relaxation. Skin temperature, systemic vascular resistance, cardiac output, plasma levels of norepinephrine and epinephrine, oxygen consumption, respiratory rate, and pulmonary wedge pressure were measured before and after the biofeedback session. Control patients had the same measurements made but were not given instruction in biofeedback-relaxation techniques. RESULTS: Patients in the biofeedback-relaxation and control groups had comparable clinical profiles at baseline. Patients undergoing biofeedback-relaxation showed the following changes: (1) increase in skin temperature of 3.1 +/- 2.8 degrees F (1.7 +/- 1.5 degrees C) in the finger and 1.5 +/- 5.2 degrees F (0.4 +/- 1.2 degrees C) in the foot, (2) increase in cardiac output of 0.30 +/- 0.33 L/min, (3) decrease in systemic vascular resistance of 152 +/- 225 dyne.sec.cm-5, and (4) decrease in respiratory rate of 4.5 +/- 3.2 breaths per minute. The biofeedback group exhibited no changes in catecholamine levels or oxygen consumption. No changes in any of these parameters were seen in the control group. DISCUSSION: Despite the presence of marked vasoconstriction in patients with advanced heart failure, a single session of biofeedback-relaxation can increase finger temperature and cardiac output and decrease systemic vascular resistance and respiratory rate, apparently without effect on systemic levels of catecholamines or oxygen consumption.