Oscillatory networks of high-level mental alignment: A perspective-taking MEG study.

Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3-7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations.

Regulation of the clock gene expression in human adipose tissue by weight loss.

BACKGROUND: The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. SUBJECTS/METHODS: Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. RESULTS: The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). CONCLUSION: Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.

Effects of high-sulphur water on hepatic gene expression of steers fed fibre-based diets.

Sulphur-induced polioencephalomalacia (sPEM), a neurological disorder affecting ruminants, is frequently associated with the consumption of high-sulphur (S) water and subsequent poor performance. Currently, there is no economical method for S removal from surface water sources, and alternative water sources are typically neither readily available nor cost-effective. Determination of genes differentially expressed in response to high-S water consumption may provide a better understanding of the physiology corresponding to high dietary S and ultimately lead to the development of treatment and prevention strategies. The objective of this study was to determine changes in gene expression in the liver, an organ important for S metabolism, of fibre-fed steers consuming high-S water. For this study, liver tissues were collected on the final day of a trial from yearling steers randomly assigned to low-S water control (566 mg/kg SO4 ; n = 24), high-S water (3651 mg/kg SO4 ; n = 24) or high-S water plus clinoptilolite supplemented at either 2.5% (n = 24) or 5.0% (n = 24) of diet dry matter (DM). Microarray analyses on randomly selected healthy low-S control (n = 4) and high-S (n = 4; no clinoptilolite) steers using the Affymetrix GeneChip Bovine Genome Array revealed 488 genes upregulated (p < 0.05) and 154 genes downregulated (p < 0.05) in response to the high- vs. low-S water consumption. Real-time RT-PCR confirmed the upregulation (p < 0.10) of seven genes involved in inflammatory response and immune functions. Changes in such genes suggest that ruminant animals administered high-S water may be undergoing an inflammation or immune response, even if signs of sPEM or compromised health are not readily observed. Further study of these, and other affected genes, may deliver new insights into the physiology underlying the response to high dietary S, ultimately leading to the development of treatments for high S-affected ruminant livestock.

Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

Sleep quality in a family with hereditary parkinsonism (PARK6).

OBJECTIVES: The autosomal recessive disorder PARK6 manifests as early-onset Parkinson's disease (PD) with a particularly mild progression. PARK6 is of particular scientific interest, since it is caused by loss-of-function mutations in the mitochondrial protein kinase PINK1 and may thus serve as a model for oxidative damage in PD and in other basal ganglia disorders. Sleep disturbances are very common in PD but have not yet been reported for PARK6 patients. The present study reports on sleep of a Spanish family with PARK6. Of the 5 siblings, 3 were homozygous and severely affected, and 2 were heterozygous and clinically asymptomatic. Research questions concerned possible differences in sleep recordings between homozygote and heterozygote siblings and similarities between PARK6 and sporadic PD sleep profiles. METHOD: The data from detailed clinical interviews of the patients and their bedpartners are reported and compared with polysomnographic data from second-night recordings. CONCLUSIONS: All siblings had good subjective and objective sleep quality. Restless legs syndrome and rapid eye movement (REM) sleep behaviour disorder (RBD) were not observed, suggesting that sleep disturbances are not commonly found in PARK6 patients. Good sleep quality and the absence of RBD might be a useful diagnostic guide in the differential diagnosis of sporadic PD versus PARK6.

Prevalence of Acanthamoeba and other naked amoebae in South Florida domestic water.

The purpose was to identify the prevalence of naked amoebae in tap water in south Florida to ascertain the risk of amoebal infections of the cornea in contact lens wearers. Over the course of a 2-year period, water samples were collected from sites throughout Broward, Palm Beach, and Dade counties, Florida. The presence of amoebae in samples was based on an enrichment cultivation method appropriate for Acanthamoeba. Amoebae were identified using diagnostic features discernable by light microscopy. A total of 283 water samples were processed and amoebae were noted in 80 of these. Acanthamoeba were found on 8 occasions (2.8%). The genera Hartmannella and Vahlkampfia, rarely involved in keratitis cases, were found in 3.5% and 2.8% of samples, respectively. A total of 19 different naked amoebae were recorded and amoebae (regardless of genus) were present in 19.4% of all samples. Previous surveys in England and Korea have shown that acanthamoebae are found in 15 to 30% of tap water samples in the home and have been associated with corneal infection in contact lens wearers. The incidence of acanthamoebae infection in the USA (2.8%) has been found to be lower than that in the UK and it has been postulated that this is related to the lack of a storage water tank in the roof loft space. However, the level of treatment of municipal water is clearly not effective at killing amoebal cysts (or trophozoites) as evidenced by the high occurrence of amoebae (19.4%) in this study.

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling.

Although atypical social behaviour remains a key characterisation of ASD, the presence of sensory and perceptual abnormalities has been given a more central role in recent classification changes. An understanding of the origins of such aberrations could thus prove a fruitful focus for ASD research. Early neurocognitive models of ASD suggested that the study of high frequency activity in the brain as a measure of cortical connectivity might provide the key to understanding the neural correlates of sensory and perceptual deviations in ASD. As our review shows, the findings from subsequent research have been inconsistent, with a lack of agreement about the nature of any high frequency disturbances in ASD brains. Based on the application of new techniques using more sophisticated measures of brain synchronisation, direction of information flow, and invoking the coupling between high and low frequency bands, we propose a framework which could reconcile apparently conflicting findings in this area and would be consistent both with emerging neurocognitive models of autism and with the heterogeneity of the condition.

Mitral valve alternans.

An echogram showing mitral valve alternans was recorded in a patient with advanced cardiomyopathy and pulsus alternans induced by premature ventricular depolarizations. Decreased left ventricular emptying by the weak beat was followed by blunting of the subsequent mitral valve E point, a finding compatible with a significant elevation of left ventricular pressure in early diastole. Both alternating systolic (contractile state) and diastolic (pressure and dimension) variables seemed to participate in the alternans phenomenon in this patient.

Changes in spontaneous sinus node rate as an estimate of cardiac autonomic tone during stable and unstable ventricular tachycardia.

Changes in sinus node rate were measured as an estimate of reflex control of cardiac autonomic tone during 32 episodes of stable ventricular tachycardia (without loss of consciousness) and 21 episodes of unstable ventricular tachycardia (loss of consciousness requiring electrical cardioversion) in 32 patients without retrograde ventriculoatrial conduction. Sinus node rate was measured before induction of ventricular tachycardia (at 5 s intervals during tachycardia) and 5 s after termination of ventricular tachycardia. It increased from 85 +/- 12 beats/min to a maximum of 109 +/- 25 beats/min during stable ventricular tachycardia (p less than 0.001) and from 82 +/- 15 beats/min to a maximum of 105 +/- 34 beats/min during unstable ventricular tachycardia (p less than 0.001). During unstable ventricular tachycardia, the increase in sinus rate was more abrupt and was followed by a sharp decrease beginning before termination of the tachycardia and resulting in a slower rate after termination (56 +/- 15 beats/min) than before tachycardia (p less than 0.001). Stable ventricular tachycardia resulted in a continuous increase of sinus node rate, which remained higher after termination (102 +/- 15 beats/min) than before tachycardia (p less than 0.001). Autonomic mechanisms responsible for changes in sinus rate were evaluated by reinducing the ventricular tachycardia after beta-adrenergic blockade by propranolol in 10 patients. Intravenous propranolol (mean dose 11 +/- 4 mg) had no effect on the magnitude of increase in sinus rate (+18 +/- 6 beats/min before and +17 +/- 7 beats/min after propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac manifestations of cocaine abuse: a cross-sectional study of asymptomatic men with a history of long-term abuse of "crack" cocaine.

OBJECTIVES: The objective of this study was to evaluate the prevalence of cardiac abnormalities in young, asymptomatic long-term "crack" cocaine abusers. BACKGROUND: Although the cardiac complications of cocaine abuse have received widespread attention, the prevalence of cardiac abnormalities in asymptomatic long-term cocaine abusers is unknown. METHODS: History, physical examination, electrocardiogram (ECG) and echocardiogram were performed in 52 consecutive long-term cocaine abusers admitted to a drug rehabilitation program. Findings were compared with those in 14 age-matched normal volunteers and 14 age-matched normotensive patients admitted to a psychiatric service who had a pattern of smoking and alcohol consumption similar to that of the study patients. RESULTS: The ECG findings were abnormal in 29% of cocaine abusers, and included nonspecific ST-T wave changes in 15%, abnormal ST segment elevation in 10%, old inferior infarction in 2%, old anteroseptal infarction in 2% and abnormal precordial R wave progression in 10%. When compared with normal volunteers and control patients, cocaine abusers had increased left ventricular posterior wall thickness (1.12 vs. 0.76 and 0.85 cm, respectively, p < 0.0001), increased septal thickness (1.13 vs. 0.76 and 0.86 cm, p < 0.001) and higher left ventricular mass index (142 vs. 84 and 94 g/m2, p < 0.0001). Left ventricular diastolic filling variables did not differ significantly among the three groups. Diastolic filling variables were similar in cocaine abusers with and without left ventricular hypertrophy, and the prevalence of left ventricular hypertrophy did not differ significantly between those who used no alcohol or < 35 ml/week of alcohol and those who consumed > or = 500 ml/week of alcohol. Left ventricular segmental wall motion abnormalities were present in 11 subjects (21%) and the ejection fraction was decreased (< 0.45) in 2 (4%). CONCLUSIONS: Electrocardiographic and echocardiographic abnormalities are common in long-term cocaine abusers. Despite the frequent occurrence of left ventricular hypertrophy, Doppler-derived diastolic filling pattern was not altered. Concomitant alcohol use did not affect the prevalence of these abnormalities.

Reversal of left ventricular intracavitary gradient with intracavitary diastolic regurgitation in hypertrophic obstructive cardiomyopathy.

A 73 year old man presented with angina and nonsustained ventricular tachycardia. Cardiac catheterization revealed the dynamic systolic intracavitary gradient of hypertrophic obstructive cardiomyopathy. Abnormal isovolumetric relaxation resulted in the development of a diastolic gradient from the left ventricular outflow tract to the left ventricular apex accompanied by intracavitary regurgitation of contrast material from the outflow tract to the left ventricular body during left ventriculography. This case provides hemodynamic and angiographic confirmation of abnormal isovolumetric relaxation in this syndrome and insight into its mechanism.

Procainamide pharmacokinetics in patients with acute myocardial infarction or congestive heart failure.

Abnormal procainamide pharmacokinetics (prolonged half-life and decreased volume of distribution) and pharmacodynamics (decreased threshold for the suppression of premature ventricular complexes) have been suggested in patients with acute myocardial infarction or congestive heart failure, or both. To better define procainamide kinetics, 37 patients in the acute care setting received intravenous procainamide (25 mg/min, median dose 750 mg) with peak and hourly blood samples taken over 6 hours. Compared with the 10 control patients, the 12 patients with acute myocardial infarction and the 15 patients with congestive heart failure had normal procainamide pharmacokinetics with respect to half-life (2.3 +/- 1.0, 2.5 +/- 0.9 and 2.6 +/- 0.8 hours, respectively), volume of distribution (1.9 +/- 0.7, 1.8 +/- 0.4 and 1.8 +/- 0.5 liters/kg, respectively), clearance (11.3 +/- 7.5, 9.3 +/- 3.6 and 9.1 +/- 3.5 ml/min per kg, respectively) and unbound drug fraction (66 +/- 9, 66 +/- 9 and 69 +/- 4%, respectively). Low thresholds for greater than 85% premature ventricular complex suppression were confirmed in these patients (median 4.7 micrograms/ml in patients with acute myocardial infarction and 3.3 micrograms/ml in patients with congestive heart failure). Thus, differences in the response of premature ventricular complexes to procainamide reflect electropharmacologic differences dependent on clinical setting rather than pharmacokinetic abnormalities. Furthermore, the reduction of procainamide dosing in patients with acute myocardial infarction or congestive heart failure, based solely on prior kinetic data, may result in inappropriate antiarrhythmic therapy.

Outcome of resuscitation from bradyarrhythmic or asystolic prehospital cardiac arrest.

Previous studies of outcome as a function of the initial electrophysiologic mechanisms recorded at the scene of prehospital cardiac arrest have demonstrated that bradyarrhythmias and asystole have the worst prognosis. In this report, our observations in bradyarrhythmic and asystolic arrests occurring from 1980 to 1982 are compared with those from 1975 to 1978. From 1980 to 1982, 61 (27%) of 225 cardiac arrest events meeting entry criteria for the study were bradyarrhythmic or asystolic. Only 2 (8%) of 24 patients with asystole and 1 (20%) of 5 patients with sinus bradycardia survived prehospital intervention. Only 1 of these 29 patients was discharged from the hospital alive. In contrast, 15 (47%) of 32 patients who presented with idioventricular rhythm at initial contact survived prehospital intervention and were hospitalized, and 8 (25%) of these 32 were ultimately discharged alive. When compared with the 1975 to 1978 patients with bradyarrhythmia and asystole, both prehospital survival (8 versus 30%, p less than 0.001) and survival after hospitalization (0 versus 15%, p less than 0.05) significantly improved, but the improvement occurred predominantly in the subgroup with idioventricular rhythm. Survivors within this subgroup tended to have a prompt response to prehospital pharmacologic interventions that were not available to the 1975 to 1978 group. The response was manifested by return to a sinus mechanism or increase in the rate of idioventricular rhythm. In conclusion, outcome has improved for a specific subgroup of victims of prehospital cardiac arrest with bradyarrhythmia or asystole; the improved outcome may relate to field interventions by rescue personnel at the scene of arrest but the mortality rate is still high.

Ambulatory electrocardiography. A cost per management decision analysis.

BACKGROUND: This study evaluated the current clinical use and costs of ambulatory electrocardiographic (AECG) monitoring for arrhythmia detection based on a cost per management decision analysis. METHODS: Consecutive inpatient and outpatient 24-hour AECGs (n = 650) performed during the calendar year 1991 were retrospectively reviewed for clinical indication, arrhythmia detection, diary information, and whether a management decision that might alter patient outcome was derived from the data. The cost per management decision (based on a representative reimbursement of $550 per AECG) and the cost index (CI) (all tests divided by useful tests) were calculated. RESULTS: Although arrhythmias were identified in 91% of the patients, management decisions were indicated in only 18% (cost per decision, $2974; CI = 5.4). Management decisions were most often derived from the data in patients being evaluated for arrhythmia therapy (37 of 37 patients; cost per decision, $550; CI = 1). Symptoms and arrhythmias were correlated in only 11 patients (2%). More often typical clinical symptoms were present (26 patients) in the absence of an arrhythmia. Of 101 AECGs following a cerebrovascular event, four had unsuspected atrial fibrillation (cost per decision, $13,888; CI = 25.0). Dizziness or lightheadedness associated with other cardiac symptoms was more likely to lead to a management decision than the same symptoms in isolation (29% vs 7%; P < .05). No patient had central nervous system symptoms correlated with an arrhythmia during the recording period or unsuspected ventricular tachycardia. CONCLUSION: Ambulatory electrocardiography has a highly variable and indication-dependent effectiveness and cost. The results suggest a strategy for improving the use of AECG based on knowing what testing indications are more likely to lead to useful clinical information.

Decreased quinidine plasma protein binding during hemodialysis.

Quinidine binding to serum proteins was quantitated in 10 regularly dialyzed patients with end-stage renal disease, both under baseline conditions and after heparin during a single hemodialysis. Quinidine binding was determined in vitro, after the addition of 2 micrograms/ml quinidine sulfate, by ultrafiltration combined with spectrophotofluorometry. The baseline percent unbound quinidine concentration in our patients was 6.5 +/- 2.3% (mean +/- SD), a value lower than in normal subjects (9.9 +/- 3.0%, n = 18, p less than 0.005). Binding correlated with both serum albumin (r = 0.72, p less than 0.02) and free fatty acid (r = 0.65, p less than 0.05) concentrations. After heparin there was a rise in percent unbound quinidine (12.2 +/- 5.6%, p less than 0.025) and in free fatty acid concentration (1111 +/- 1202 microEq/l, p = 0.004) in each subject. After heparin the relationship between quinidine binding and free fatty acid concentration was again evident (r = 0.97, p less than 0.001). Dynamic changes in the levels of free quinidine, as well as other drugs during hemodialysis, may require adjustments to avoid toxicity and adverse interactions.

Blood collection techniques, heparin and quinidine protein binding.

With the use of glass syringes without heparin and all glass equipment, the percent of unbound quinidine was measured by ultrafiltration and a double-extraction assay method after addition of 2 microgram/ml of quinidine sulfate. Compared to the all-glass method, collection of blood using Vacutainers resulted in an erroneous and variable decrease in quinidine binding related to blood to rubber-stopper contact. With glass, the unbound quinidine fraction was (mean +/- standard error) 10 +/- 1% in 10 normal volunteers, 8.5 +/- 1.5% in 10 patients with congestive heart failure, and 11 +/- 2% in 11 patients with chronic renal failure (although in 8 of the latter 11 patients the percent of unbound quinidine was 4 or more standard errors from the mean of the normal group). During cardiac catheterization, patients had markedly elevated unbound quinidine fractions: 24 +/- 2% (p less than 0.001). This abnormality coincided with the addition of heparin in vivo and was less apparent after the addition of up to 10 U/ml of heparin in vitro (120% and 29% increase in unbound quinidine fractions, respectively). Quinidine binding should be measured with all glass or equivalent equipment.

Procainamide elimination kinetics in pediatric patients.

Procainamide kinetics were studied in six children after a single intravenous dose. Two-compartment kinetic analysis of serum concentration-time curves of five children, who received a dose of 5.5 +/- 0.9 mg/kg (mean +/- SD), revealed the following values for kinetic parameters: distribution half-life, 10.3 +/- 3.4 min; elimination half-life, 1.7 +/- 0.1 hr; elimination constant, 1.2 +/- 0.3 hr-1; plasma clearance 19.4 +/- 2.0 ml/min/kg, and steady-state volume of distribution, 2.2 +/- 0.3 l/kg. A sixth patient, who received an accidental overdose of 28 mg/kg, had altered elimination kinetics due to drug-induced hypotension. N-acetylprocainamide (NAPA) was detected in serum samples obtained soon after procainamide dosing and peak concentrations were attained at 1 to 2 hr. NAPA levels were lower than corresponding procainamide concentrations at most sampling periods. The findings of short elimination half-life and rapid plasma clearance of procainamide in children suggest that continuous intravenous infusion may be necessary to maintain therapeutically effective plasma concentrations in these patients.

Clinical use of the antipsychotics.

Neuroleptics are the cornerstone for both the acute treatment and prevention of most schizophrenic episodes. The authors review the current practical information available for the clinical management of acute episodes and maintenance therapy, including dosage schedules, plasma level determinations, and side effects. All neuroleptics given in equivalent doses produce approximately the same degree of antipsychotic activity. The most common cause of treatment failure in acute psychosis is an inadequate dose, and the most common cause of relapse is patient noncompliance. Maintenance medication should be given at the lowest dose that will sustain improvement. The authors also discuss several new alternative drug treatments to neuroleptics.

Congestive heart failure: echocardiographic insights.

This study was designed to assess the role of echocardiography in the evaluation and management of patients with the congestive heart failure syndrome. Fifty consecutive patients with congestive heart failure referred for echocardiography were evaluated. Thirty patients (60 percent) had ejection fractions under 50 percent (mean +/- SD 30 +/- 9 percent), left ventricular dilatation (6.5 +/- 0.7 cm), and normal wall thicknesses (1.0 +/- 0.2 cm). The echocardiographic findings were predictable on clinical grounds in 18 of the 30 patients (60 percent) and worse than clinically expected in 12 patients (40 percent). Management changes after echocardiography were indicated in 11 of 30 patients (37 percent). The remaining 20 of the 50-patient cohort (40 percent) had ejection fractions above 50 percent (mean 70 +/- 9 percent, p less than 0.01), and, as a group, were characterized by normal left ventricular size (5.1 +/- 0.8 cm, p less than 0.01) and borderline wall thicknesses (1.1 +/- 0.2 cm, p less than 0.01). The largest subgroup of these 20 patients had hypertensive heart disease (seven patients, 35 percent) associated with the congestive heart failure syndrome presumably related to left ventricular diastolic (compliance) dysfunction. The normal ejection fraction was unexpected clinically in 18 of these 20 patients (90 percent). Recommended management after echocardiography changed in all 18 patients. Since standard clinical findings (history, physical examination, and chest roentgenography) failed to separate patients with normal and abnormal ejection fractions, or those in need of changes in management, echocardiography was a useful and, at times, essential part of the evaluation of these patients with the congestive heart failure syndrome.

Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care.

PURPOSE: Clinical and radiographic examinations are commonly used for estimating severity and titrating therapy of chronic congestive heart failure. The purpose of this study was to establish the relationship between findings on history, physical examination, chest roentgenogram, and pulmonary capillary wedge pressure (PCWP). PATIENTS AND METHODS: Fifty-two consecutive patients with chronic congestive heart failure, referred for evaluation for heart transplantation, were studied; all patients underwent history, physical examination, upright chest roentgenogram, and cardiac catheterization. The mean left ventricular ejection fraction was 0.19 +/- 0.06. Patients were divided into three groups according to their PCWP: Group 1, normal PCWP (less than or equal to 15 mm Hg, n = 19); Group 2, mild to moderately elevated PCWP (16 to 29 mm Hg, n = 15); Group 3, markedly elevated PCWP (greater than or equal to 30 mm Hg, n = 18). RESULTS: Physical and radiographic signs of congestion were more common in the groups with higher PCWP, but they could not be used to reliably separate patients with different filling pressures. Physical findings (orthopnea, edema, rales, third heart sound, elevated jugular venous pressure) or radiographic signs (cardiomegaly, vascular redistribution, and interstitial and alveolar edema) had poor predictive value for identifying patients with PCWP values greater than or equal to 30 mm Hg. These findings had poor negative predictive value to exclude significantly elevated PCWP (greater than 20 mm Hg). Radiographic pulmonary congestion was absent in eight (53%) patients in Group 2 and seven (39%) in Group 3. In patients in Group 2 and 3, those without radiographic congestion were in a better New York Heart Association functional class (3.5 +/- 0.5 versus 2.8 +/- 0.6, p less than 0.01). There was good correlation between right atrial pressure and PCWP (r = 0.64, p less than 0.001). A normal right atrial pressure had no predictive value, but a pressure greater than 10 mm Hg was seen in all but one patient with a PCWP value greater than 20 mm Hg. CONCLUSION: Clinical, radiographic, and hemodynamic evaluations of chronic congestive heart failure yield conflicting results. Absence of radiographic or physical signs of congestion does not ensure normal PCWP values and may lead to inaccurate diagnosis and inadequate therapy. It is not known whether therapy aimed at normalizing PCWP is superior to relieving clinical and radiographic signs of congestion.