Carotid sinus "irritability" rather than hypersensitivity: a new name for an old syndrome?

Carotid sinus hypersensitivity (CSH) is a well-described cause of syncope, resulting in bradycardia and/or hypotension in response to neck pressure. The authors hypothesized that (CSH) represents an inappropriate response of the baroreflex system to a nonphysiologic stimulus, rather than a truly hypersensitive carotid sinus (ie, excessive vagotonia and sympathoinhibition in response to arterial hypertension). To test their hypothesis, the authors used a neck chamber to deliver stepped, R-wave-triggered changes in transmural carotid sinus pressure, from +40 to -60 mm Hg, during a single held expiration. The authors studied 7 men (age 69 +/- 8y; mean age +/- SD) with carotid sinus syndrome and 10 age- and sex-matched controls. Seven repetitions of pressure changes were averaged, and the carotid sinus response described by changes in the R-R interval. There was no statistical difference in carotid-cardiac baroreflex gain (R-R interval/pressure change; mean gain +/- SD, 3.0 +/- 2.1 msec/mm Hg and 2.2 +/- 3.0 msec/mm Hg, respectively) or other markers of carotid baroreflex responses between the subjects and controls. These preliminary results suggest that (CSH) may not be a "hypersensitive" reflex, but rather an inappropriate response, or "irritability," of the baroreflex system to nonphysiologic deformation of the carotid sinus and/or surrounding tissues.

Correlation of impedance minute ventilation with measured minute ventilation in a rate responsive pacemaker.

Although rate responsive pacing based on impedance minute ventilation (IMV) is now standard, there is almost no data confirming the relationship between IMV from an implanted pacemaker and measured minute ventilation (VE) during exercise. Nineteen completely paced adults implanted with Medtronic Kappa 400 pacemakers underwent symptom-limited maximal metabolic treadmill testing using a modified Minnesota Pacemaker Response Protocol. Minute ventilation (VE, L/min) was simultaneously measured using the flowmeter of a respiratory metabolic gas analysis system and the transthoracic impedance minute ventilation circuitry of the pacemaker. Correlation coefficients (r) were used to find the best fit line to describe the relationship between the two measurements. Mean (+/- SD) r values for the first, second, and third order polynomial equations and for log and exponential equations were: 0.92 +/- 0.08, 0.94 +/- 0.04, 0.95 +/- 0.04, 0.91 +/- 0.06, and 0.91 +/- 0.07, respectively. None of the r values were statistically different from the first order equation. Transthoracic IMV as measured by the Medtronic Kappa 400 is closely correlated to measured minute ventilation and is represented well by a first order (linear) equation.

A propensity analysis of cigarette smoking and mortality with consideration of the effects of alcohol.

Although it is well established that cigarette smoking causes excess mortality, the extent of the increased risk has been challenged because self-selection biases and confounding factors may not have been adequately accounted for in prior studies. We therefore performed a propensity analysis on a population-based cohort. A logistic regression model was used to generate a propensity score for current smoking in 6,099 adults (mean age 46 years, 54% men, 36% current smokers) participating in the National Heart Lung and Blood Institute's (NHLBI) Lipid Research Clinic Prevalence Study. During 12 years of follow-up, 513 subjects (8%) died. After adjusting for age, current smoking was strongly associated with death (compared with never and former smokers, relative risk [RR] 2.69, 95% confidence interval [CI] 1.98 to 0.64, p <0.0001 and RR 1.79, 95% CI 1.26 to 2.55, p = 0.001, respectively). After adjusting for a propensity score based on 27 covariates and the covariates themselves, current smoking remained strongly and independently predictive of excessive death risk in smokers compared with never and former smokers (adjusted RR 2.96, 95% CI 2.16 to 4.05, p <0.0001 and adjusted RR 1.87, 95% CI 1.31 to 2.67, p = 0.0006, respectively). Although smokers were more likely to also drink alcohol, an interaction was noted, whereby, after adjustment for propensity score and other covariates, current smoking was associated with a moderately strong increase in mortality among drinkers (adjusted RR 2.00, 95% CI 1.42 to 2.82, p <0.0001), but was also associated with a markedly increased death risk among nondrinkers (adjusted RR 4.74, 95% CI 3.24 to 6.92, p <0.0001). The independent association of smoking with death even after a rigorous propensity analysis argues that it is highly unlikely that the link between smoking and mortality is materially biased or confounded.

Heart rate recovery and treadmill exercise score as predictors of mortality in patients referred for exercise ECG.

CONTEXT: Both attenuated heart rate recovery following exercise and the Duke treadmill exercise score have been demonstrated to be independent predictors of mortality, but their prognostic value relative to each other has not been studied. OBJECTIVE: To assess the associations among abnormal heart rate recovery, treadmill exercise score, and death in patients referred specifically for exercise electrocardiography. DESIGN AND SETTING: Prospective cohort study conducted in an academic medical center between September 1990 and December 1997, with a median follow-up of 5.2 years. PATIENTS: A total of 9454 consecutive patients (mean [SD] age, 53 [11] years; 78% male) who underwent symptom-limited exercise electrocardiographic testing. Exclusion criteria included age younger than 30 years, history of heart failure or valvular disease, pacemaker implantation, and uninterpretable electrocardiograms. MAIN OUTCOME MEASURES: All-cause mortality, as predicted by abnormal heart rate recovery, defined as failure of heart rate to decrease by more than 12/min during the first minute after peak exercise, and by treadmill exercise score, defined as (exercise time) - (5 x maximum ST-segment deviation) - (4 x treadmill angina index). RESULTS: Three hundred twelve deaths occurred in the cohort. Abnormal heart rate recovery and intermediate- or high-risk treadmill exercise score were present in 20% (n = 1852) and 21% (n = 1996) of patients, respectively. In univariate analyses, death was predicted by both abnormal heart rate recovery (8% vs 2% in patients with normal heart rate recovery; hazard ratio [HR], 4.16; 95% confidence interval [CI], 3.33-5.19; chi(2) = 158; P<.001) and intermediate- or high-risk treadmill exercise score (8% vs 2% in patients with low-risk scores; HR, 4.28; 95% CI, 3.43-5.35; chi(2) = 164; P<.001). After adjusting for age, sex, standard cardiovascular risk factors, medication use, and other potential confounders, abnormal heart rate recovery remained predictive of death (among the 8549 patients not taking beta-blockers, adjusted HR, 2.13; 95% CI, 1.63-2.78; P<.001), as did intermediate- or high-risk treadmill exercise score (adjusted HR, 1. 49; 95% CI, 1.15-1.92; P =.002). There was no interaction between these 2 predictors. CONCLUSIONS: In this cohort of patients referred specifically for exercise electrocardiography, both abnormal heart rate recovery and treadmill exercise score were independent predictors of mortality. Heart rate recovery appears to provide additional prognostic information to the established treadmill exercise score and should be considered for routine incorporation into exercise test interpretation. JAMA. 2000;284:1392-1398.

Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort.

BACKGROUND: Abnormal heart rate recovery after symptom-limited exercise predicts death. It is unknown whether this is also true among patients undergoing submaximal testing. OBJECTIVE: To test the prognostic implications of heart rate recovery in cardiovascularly healthy adults undergoing submaximal exercise testing. DESIGN: Population-based cohort study. SETTING: 10 primary care sites. PARTICIPANTS: 5234 adults without evidence of cardiovascular disease who were enrolled in the Lipid Research Clinics Prevalence Study. MEASUREMENTS: Heart rate recovery was defined as the change from peak heart rate to that measured 2 minutes later (heart rate recovery was defined as < or =42 beats/min). RESULTS: During 12 years of follow-up, 312 participants died. Abnormal heart rate recovery predicted death (relative risk, 2.58 [CI, 2.06 to 3.20]). After adjustment for standard risk factors, fitness, and resting and exercise heart rates, abnormal heart rate recovery remained predictive (adjusted relative risk, 1.55 [CI, 1.22 to 1.98]) (P<0.001). CONCLUSION: Even after submaximal exercise, abnormal heart rate recovery predicts death.

Influence of posture, breathing pattern, and type of exercise on minute ventilation estimation by a pacemaker transthoracic impedance sensor.

Previous studies have shown a high correlation between transthoracic impedance minute ventilation (IMV) determined by a pacemaker sensor and actual minute ventilation (VE) measured by standard methods. We hypothesized that several factors (e.g., posture, breathing pattern, and exercise type) could potentially affect the calibration between IMV and VE. In patients with Medtronic Kappa 400 pacemakers, VE (L/min) was monitored using a standard cardiopulmonary metabolic gas analysis system with simultaneous recording of IMV (ohms/min) using DR-180 extended telemetry monitors. Effects of posture and of breathing pattern at rest (19 patients; age 60 +/- 13 years) were evaluated by monitoring each patient under three conditions: (a) slow breathing, supine, (b) slow breathing, sitting, and (c) shallow breathing, supine. Calibration at rest was defined as the ratio of IMV to VE. Effect of type of exercise on calibration compared treadmill versus graded bicycle ergometer exercise (18 patients; age 62 +/- 14 years). Calibration during exercise was defined as: (a) "Begin" (the IMV to VE ratio at VE = 10 L/min, the typical VE value at beginning of exercise), and (b) slope of the IMV/VE regression line. Calibration of IMV/VE was significantly smaller for sitting versus supine position (0.7130.177, P < 0.001) and for shallow versus slow breathing (0.7210.373, P < 0.001), and larger for treadmill versus bicycle exercise (Begin: 1.240.43, P = 0.018; Slope: 1.260.42, P = 0.013). In conclusion, posture, breathing pattern, and type of exercise affect the IMV estimation of the actual VE, possibly by altering the static or dynamic geometry (thus, the impedance) of the intrathoracic viscera.

Heart-rate recovery immediately after exercise as a predictor of mortality.

BACKGROUND: The increase in heart rate that accompanies exercise is due in part to a reduction in vagal tone. Recovery of the heart rate immediately after exercise is a function of vagal reactivation. Because a generalized decrease in vagal activity is known to be a risk factor for death, we hypothesized that a delayed fall in the heart rate after exercise might be an important prognostic marker. METHODS: For six years we followed 2428 consecutive adults (mean [+/-SD] age, 57+/-12 years; 63 percent men) without a history of heart failure or coronary revascularization and without pacemakers. The patients were undergoing symptom-limited exercise testing and single-photon-emission computed tomography with thallium scintigraphy for diagnostic purposes. The value for the recovery of heart rate was defined as the decrease in the heart rate from peak exercise to one minute after the cessation of exercise. An abnormal value for the recovery of heart rate was defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise. RESULTS: There were 213 deaths from all causes. A total of 639 patients (26 percent) had abnormal values for heart-rate recovery. In univariate analyses, a low value for the recovery of heart rate was strongly predictive of death (relative risk, 4.0; 95 percent confidence interval, 3.0 to 5.2; P<0.001). After adjustments were made for age, sex, the use or nonuse of medications, the presence or absence of myocardial perfusion defects on thallium scintigraphy, standard cardiac risk factors, the resting heart rate, the change in heart rate during exercise, and workload achieved, a low value for heart-rate recovery remained predictive of death (adjusted relative risk, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). CONCLUSIONS: A delayed decrease in the heart rate during the first minute after graded exercise, which may be a reflection of decreased vagal activity, is a powerful predictor of overall mortality, independent of workload, the presence or absence of myocardial perfusion defects, and changes in heart rate during exercise.

Consequences of incomplete carbohydrate absorption from fruit juice consumption in infants.

BACKGROUND: Most infants consume fruit juices by 6 months of age. However, fruit juices containing sorbitol may be associated with carbohydrate malabsorption without clinical symptoms. We hypothesized that increased physical activity and metabolic rate may be associated with carbohydrate malabsorption. METHODS: Physical activity and metabolic rate were determined in 14 healthy infants ([mean +/- SD] age, 5.1 +/- 0.8 months; weight, 7.8 +/- 1.1 kg; length, 67 +/- 4.2 cm; and body fat, 26% +/- 5%) for 3 hours in a respiratory chamber. Seven were fed pear juice, and the other 7 were fed white grape juice (120 mL) after a 2-hour fast. Pear juice contains sorbitol and a high fructose-glucose ratio, whereas white grape juice is sorbitol free and has a low fructose-glucose ratio. Carbohydrate absorption was determined by breath hydrogen gas analysis. The study was double-blinded. RESULTS: When compared with the infants without carbohydrate malabsorption (peak breath hydrogen level < 20 ppm above baseline), 5 of the 7 infants fed pear juice and 2 of the 7 infants fed white grape juice exhibited carbohydrate malabsorption (peak breath hydrogen level > or = 20 ppm above baseline; P < .01). These infants also exhibited both increased physical activity (P < .001) and metabolic rate (P < .05) after juice consumption in comparison with infants with normal carbohydrate absorption. When grouped according to the type of juice consumed, only infants fed pear juice exhibited increases in physical activity (P < .01). CONCLUSIONS: Carbohydrate malabsorption is associated with increased physical activity and metabolic rate in infants. Most of the infants who had carbohydrate malabsorption consumed pear juice. Therefore, fruit juices containing sorbitol and high levels of fructose may not be optimal for young infants.

Comprehensive assessment of the components of energy expenditure in infants using a new infant respiratory chamber.

BACKGROUND: Current methods for energy expenditure (EE) measurements in term infants do not include simultaneous measurements of basal and sleeping metabolic rates (BMR and SMR) or a measure of physical activity (PA). Furthermore, prediction equations for calculating EE are not appropriate for use in infants with metabolic disorders. OBJECTIVE: To develop and utilize a new infant respiratory chamber for simultaneous measurements of EE (kJ/d), preprandial BMR (kJ/d), SMR (kJ/d) and an index of PA (oscillations/min/kg body weight) in infants with a variety of metabolic disorders, for up to four hours in a hospital setting, while allowing parental interaction in a comfortable environment. METHODS: We obtained simultaneous measurements of EE, BMR, SMR and PA in 21 infants (66+/-73 days of age, 4.5+/-1.7 kg body weight, 55+/-8 cm in length and 16+/-7% body fat) using our new infant respiratory chamber. Six of these infants were healthy, seven had thyroid dysfunction, five were HIV-exposed, one had AIDS, one had intrauterine and postnatal growth retardation and one was a hypothermic preterm infant. Energy expenditure, BMR and SMR were extrapolated for 24 hours. Body composition was estimated by skin-fold thickness, using age-appropriate formulae. Basal metabolic rate obtained with the infant respiratory chamber was compared to BMR that was calculated using the appropriate World Health Organization (WHO) equations. RESULTS: In all infants both extrapolated 24-hour EE and BMR correlated with fat-free mass (r = 0.89, p<0.01 and r = 0.88, p<0.01 respectively). Twenty-four hour EE also correlated with PA (r = 0.52, p<0.05). The HIV-exposed infants had higher BMR (p<0.05) than that calculated by the appropriate WHO equation. We found that the caloric requirements for the infant with growth retardation were underestimated based on the infant's weight and age. CONCLUSIONS: The infant respiratory chamber can measure all of the main components of EE. Some of the results obtained differed significantly from those obtained by the WHO equations; therefore, the new infant respiratory chamber is necessary for estimating EE in infants with metabolic and growth disorders.

Angio-proliferative lesions in a homosexual boar with features resembling Kaposi's sarcoma.

Clinical, biopsy and necropsy studies of a homosexual boar revealed angio-proliferative lesions in the skin of the thigh, scrotum and the inguinal lymph node. Angiofibromas were identified in the dermis and subcutis of the thorax and mandible. The avidin-biotin-peroxidase complex technique demonstrated Factor VIII-related antigen as a marker for the neoplastic endothelial cells of the tumors. This boar also showed weight loss and lymphopenia. Explants of tumors were maintained in cultures for 22 passages and cultured cells produced tumors when injected subcutaneously into nude mice. No viral antigen was detected in the cultured tumor cells. Similarities and differences between the lesions in the boar and human Kaposi's sarcoma are discussed.

Simultaneous evaluation of pancreatic exocrine function and intestinal absorptive function in dogs with chronic diarrhea.

The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA):xylose test was evaluated in 5 clinically normal dogs, 5 dogs with pancreatic exocrine insufficiency (PEI), and 7 dogs with intestinal malabsorption. A solution of BT-PABA (1 g/100 ml) and d-xylose (10 g/100 ml) was given orally (5 ml/kg of body weight) to dogs in each group. Plasma p-aminobenzoic acid (PABA) curves were decreased in dogs with PEI and intestinal malabsorption (P < 0.05) but were the lowest in dogs with PEI, compared with clinically normal dogs. Xylose values in dogs with malabsorption were decreased (P < 0.05), compared with clinically normal dogs. Dogs with PEI had plasma xylose values that were intermediate to values in clinically normal dogs and dogs with intestinal malabsorption. Results of BT-PABA:xylose testing were compared with results of sodium PABA:xylose testing, to determine whether decreased PABA values obtained by the BT-PABA:xylose test were caused by free PABA malabsorption or by maldigestion of BT-PABA. The sodium PABA:xylose test was performed in dogs from each group by oral administration of a solution (5 ml/kg) of sodium PABA (0.372 g/100 ml) and d-xylose (10.0 g/100 ml). Plasma PABA values obtained by the sodium PABA:xylose test were similar in each group. Thus, different PABA values obtained by the BT-PABA:xylose test were not caused by PABA malabsorption. Xylose values were similar to values obtained by the BT-PABA:xylose test. It was concluded that: (1) the BT-PABA:xylose test is a practical test for detecting maldigestion or malabsorption in the dog; (2) dogs with intestinal malabsorption may have functional PEI; and (3) decreased PABA plasma values obtained by BT-PABA:xylose testing are not caused by malabsorption of free PABA.