Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis.

BACKGROUND: The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. METHODS: The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. RESULTS: The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs. CONCLUSION: Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.

Plasma metabolomic profiling of hypertrophic cardiomyopathy patients before and after surgical myectomy suggests postoperative improvement in metabolic function.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. We hypothesized that metabolomic biomarkers for LVOT obstruction may be detectable in plasma from HCM patients. METHODS: We conducted metabolomic profiling on plasma samples of 18 HCM patients before and after surgical myectomy, using a commercially available metabolomics platform. RESULTS: We found that 215 metabolites were altered in the postoperative state (p-value < 0.05). 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value < 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved organ metabolic function and increased lean soft tissue mass. CONCLUSIONS: These findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.

Evaluation of N-terminal prohormone of brain natriuretic peptide and cardiac troponin-I levels in cats with systolic anterior motion of the mitral valve in the absence of left ventricular hypertrophy.

OBJECTIVES: To identify the prevalence of systolic anterior motion of the mitral valve (SAM) in apparently healthy cats in the absence of left ventricular hypertrophy (LVH) and examine the relationship between specific cardiac biomarker concentrations and echocardiographic parameters in these individuals. ANIMALS: eighty client-owned cats. MATERIALS AND METHODS: retrospective study; inclusion criteria were the presence of SAM on conscious echocardiography and concurrent measurement of plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and serum cardiac troponin-I (cTnI). Cats were excluded if they had LVH, left atrial enlargement or systemic disease. The percentages of cats with NT-proBNP and cTnI concentrations above the normal reference range were calculated. The correlation between each biomarker concentration and left ventricular myocardial wall thickness, left atrial size and maximum left ventricular outflow tract velocity was evaluated. RESULTS: Thirty-four of 80 patients with SAM showed no evidence of cardiac remodelling (LVH or left atrial enlargement). Of these patients, 30 of 34 had elevated NT-proBNP, and cTnI was elevated in 13 of 27 (48.1%) cats where this biomarker was measured in association with the NT-proBNP assay. A positive correlation was observed between concentration of plasma NT-proBNP and maximum left ventricular outflow tract velocity (rs = 0.67, p<0.0001). No significant correlations were found between the concentration of biomarkers and the remaining echocardiographic parameters. CONCLUSIONS: SAM is frequently observed in cats even in the absence of cardiac remodelling, and these individuals often demonstrate elevated plasma NT-proBNP and serum cTnI concentrations. Plasma NT-proBNP elevation is correlated with the severity of the left ventricular outflow obstruction caused by SAM.

Preoperative NT-proBNP Predicts Midterm Outcome After Septal Myectomy.

Background The prognostic value of N-terminal pro-brain natriuretic peptide ( NT -pro BNP ) in patients with hypertrophic cardiomyopathy who underwent septal myectomy has not been well studied. Methods and Results We retrospectively evaluated NT -pro BNP levels in 758 patients (46.1±13.8 years; median follow-up, 936 days) who underwent septal myectomy in our center between March 2011 and April 2018. The median NT -pro BNP level was 1450.5 (interquartile range 682.6-2649.5) pg/mL. Overall, 22 (2.9%) patients died during follow-up; of these, 86.4% were cardiovascular deaths. The 3-year survival free from all-cause mortality by tertile was 95.2% (95% CI 91.1% to 97.4%; NT -pro BNP >2080 pg/mL), 98.3% (95% CI 94.6% to 99.5%; NT -pro BNP , 947-2080 pg/mL), and 99.2% (95% CI , 94.4% to 99.9%; NT -pro BNP <947 pg/mL). The 3-year survival rate free from cardiovascular mortality by tertiles was 95.2% in the highest tertile, 98.8% in the middle tertile, and 99.2% in the lowest tertile. Cox regression analysis indicated that Ln( NT -pro BNP ) was a significantly independent predictor of all-cause mortality (hazard ratio 2.380, 95% CI 1.356-4.178, P=0.003) and cardiovascular mortality (hazard ratio 2.788, 95% CI 1.450-5.362, P=0.002). In addition, concomitant coronary artery bypass grafting for coronary artery disease was also an independent predictor of cardiovascular mortality (hazard ratio 5.178, 95% CI 1.597-16.789, P=0.006). Conclusions Increased preoperative NT -pro BNP level is a strong predictor of midterm mortality in patients undergoing septal myectomy.

Associations Between Multiple Circulating Biomarkers and the Presence of Atrial Fibrillation in Hypertrophic Cardiomyopathy with or Without Left Ventricular Outflow Tract Obstruction.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Data regarding the correlations of biomarkers and AF in HCM patients are rather limited. We sought to explore the associations between the presence of AF and circulating biomarkers reflecting cardiovascular function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), endothelial function (big endothelin-1, big ET-1), inflammation (high-sensitivity C-reactive protein), and myocardial damage (cardiac troponin I, cTnI) in HCM patients with and without left ventricular outflow tract obstruction (LVOTO).In all, 375 consecutive HCM in-hospital patients were divided into an AF group (n = 90) and a sinus rhythm (SR) group (n = 285) according to their medical history and electrocardiogram results.In comparison with the SR group, peripheral concentrations of big ET-1, NT-pro BNP, and cTnI were significantly higher in patients with AF. Only the biomarker of big ET-1, together with palpitation and left atrial diameter (LAD), was independently associated with AF in HCM patients. Ln big ET-1 was positively related to Ln NT-pro BNP, LAD, and heart rate, but negatively related to left ventricular ejection fraction. Combined measurements of big ET-1 ≥ 0.285 pmol/L and LAD ≥ 44.5 mm indicated good predictive values in the presence of AF, with a specificity of 94% and a sensitivity of 85% in HCM patients.Big ET-1 has been identified as an independent determinant of AF, regardless of LVOTO, and is significantly related to parameters representing cardiac function and remodeling in HCM. Big ET-1 might be a valuable index to evaluate the clinical status of AF in HCM patients.

Mitochondrial long noncoding RNAs as blood based biomarkers for cardiac remodeling in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease with a high risk for sudden cardiac death in young people. As a subtype, hypertrophic obstructive cardiomyopathy (HOCM) additionally has a left ventricular outflow gradient, showing stronger symptoms and requires a different treatment compared with hypertrophic nonobstructive cardiomyopathy (HNCM). In this study our aim was to investigate the regulation of mitochondrial and cardiac remodeling associated long noncoding RNAs (lncRNAs) in blood of patients affected with HOCM and HNCM. We included 28 HNCM, 57 HOCM, and 26 control inviduals. Already known mitochondrial and cardiac remodeling associated lncRNAs uc004cos.4, uc004coz.1, uc004cov.4, uc011mfi.2, uc022bqw.1, uc022bqs.1, and uc022bqu.1 were amplified in serum of these patients and correlated with clinical parameters. Long noncoding RNAs uc004cov.4 and uc022bqu.1 were significantly increased in patients with HOCM but not in patients with HNCM. With the use of receiver operator characteristic (ROC) curve analysis, lncRNAs uc004cov.4 and uc022bqu.1 were able to identify HOCM patients. In our study we evidenced that the specific mitochondrial long noncoding RNAs uc004cov.4 and uc022bqu.1 were upregulated in patients with HOCM and they were also able to identify HOCM and could be developed as useful clinical biomarkers in the future.

Erythrocyte creatine as a marker of intravascular hemolysis due to left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

BACKGROUND: Erythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG). METHODS AND RESULTS: We measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36µmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG (r=0.437, p<0.001). If erythrocyte creatine levels are high (≥1.8µmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver (r=0.125, p=0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver (r=0.695, p=0.001). CONCLUSIONS: There is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities.

Increased mean platelet volume in hypertrophic cardiomyopathy.

Thromboembolic events may be seen in patients with hypertrophic cardiomyopathy (HCM). We investigated the mean platelet volume (MPV), an indicator of platelet activation in patients with HCM. This study included 112 patients with HCM, in which 40 were patients with hypertrophic obstructive cardiomyopathy (HOCM), and 106 were control participants. The MPV was significantly higher in patients with HCM than in controls (9.1 ± 0.3 vs 7.9 ± 0.3 fL, P = .01). In the subgroup analyses, MPV was also higher in patients with HOCM compared to those with hypertrophic nonobstructive cardiomyopathy (HNCM; 9.3 ± 0.3 vs 9.0 ± 0.2 fL, P = .01). Similarly, patients with HNCM had higher MPV values than controls (9.0 ± 0.2 vs 7.9 ± 0.3 fL, P = .01). The MPV was significantly and positively correlated with left ventricular outflow tract (LVOT) obstruction (r = .42, P = .001) and septal thickness (r =.62, P = .001). In linear regression analysis, MPV was independently associated only with septal thickness (ß = .07, 95% confidence interval: 0.04-0.09, P = .001). The MPV can be elevated in patients with HCM regardless of the obstruction of LVOT and may be associated with the severity of septal thickness.

Importance of adhesion molecules for children with congenital heart disease.

BACKGROUND: The aim of our study was to compare the blood levels of adhesion molecules in children with different heart diseases and pulmonary flow rates. METHODS: In this study, we evaluated the levels of soluble intercellular adhesion molecule-1 and soluble vascular cellular adhesion molecule-1 in blood samples of 65 children with different congenital heart diseases. The patients were divided into four groups according to their pulmonary blood flow. The first group had increased pulmonary blood flow with pulmonary hypertension and left-to-right shunt. The second group had increased pulmonary blood flow without pulmonary hypertension and left-to-right shunt. The third group had decreased pulmonary blood flow with cyanotic congenital heart disease and the fourth group had normal pulmonary blood flow with left ventricle outflow tract obstruction and aortic stenosis. RESULT: The highest soluble intercellular and vascular cellular adhesion molecule-1 levels with the mean values of 420.2 nanograms per millilitre and 1382.1 nanograms per millilitre, respectively, were measured in the first group and the lowest levels with the mean values of 104.4 and 358.6 nanograms per millilitre, respectively, were measured in the fourth group. The highest pulmonary blood pressure levels were found in the first group. CONCLUSION: Endothelial activity is influenced not only by left-to-right shunt with pulmonary hypertension, but also by decreased pulmonary blood flow in cyanotic heart diseases. Adhesion molecules are valuable markers of endothelial activity in congenital heart diseases, and they are influenced by pulmonary blood flow rate.

Endogenous catecholamine levels and function of the systemic right ventricle following atrial switch.

BACKGROUND: As a result of successful surgery there is a large cohort of young adults with systemic right ventricles, suffering from progressive right ventricular dysfunction. Beta-blockers are successfully used in left ventricular failure. We assessed catecholamine levels and related it to cardiac function late following atrial switch, to provide the pathophysiologic basis for pharmacotherapy in patients with systemic right ventricles. METHODS: It was a prospective study of 23 consecutive adult patients with the complete transposition of the great arteries, following atrial switch. Epinephrine and norepinephrine concentrations were measured with high performance liquid chromatography. RESULTS: Mean+/-SD epinephrine and norepinephrine levels were 54.5+/-29.0 pg/mL and 389.6+/-134.2 pg/mL, respectively. In multivariate stepwise regression models, sex (B=-0.455, 95% CI for B of -0.887 to -0.023, P=0.04), age (B=-1.328, 95% CI for B of -2.402 to -0.254, P=0.018), and cardiothoracic ratio (B=2.302, 95% CI for B of 0.120-4.484, P=0.04) were significant predictors of epinephrine levels. Diastolic right ventricular cavity area (B=0.024, 95% CI for B of 0.009-0.038, P=0.003) was a significant predictor of norepinephrine levels. Significantly higher levels of epinephrine were observed in patients with vs without left ventricular tract obstruction (88.0+/-15.5 vs 47.4+/-26.2 pg/mL, P=0.008). CONCLUSIONS: We have demonstrated a significant correlation between right ventricular enlargement and epinephrine as well as norepinephrine levels. Elevated catecholamine levels were observed in patients with left ventricular tract obstruction. This supports the use of beta-blockers in the selected patients with systemic right ventricles following atrial switch.

Enhanced oxidative stress in hypertrophic cardiomyopathy.

Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated with enhanced oxidative stress. We enrolled 54 HCM patients with sinus rhythm, including 21 subjects with a left ventricular outflow tract (LVOT) obstruction (gradient >/= 30 mmHg), and 54 age- and sex-matched controls without cardiovascular diseases. Serum levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a stable marker of oxidative stress, were determined. Serum 8-iso-PGF(2alpha) levels were elevated in HCM patients compared with controls (35.4 +/- 10.2 vs. 29.9 +/- 9.9 pg/ml, p < 0.001). Patients with obstructive HCM displayed higher 8-iso-PGF(2alpha) levels compared with the non-obstructive HCM subgroup (41.6 +/- 12.7 vs. 31.4 +/- 5.4 pg/ml, p < 0.0001). Both anatomic (mitral-septal distance) and hemodynamic (subaortic gradient) indexes of LVOT obstruction, but not other echocardiographic variables, correlated with 8-iso-PGF(2alpha) levels (r = -0.43; p < 0.05 and r = 0.39; p < 0.05, respectively). This study is the first to show that HCM is characterized by enhanced oxidative stress as evidenced by higher 8-iso-PGF(2alpha), which achieves its highest values in the presence of LVOT obstruction in HCM patients.

Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction.

BACKGROUND: Hypertrophic obstructive cardiomyopathy submits blood to conditions of high shear stress. High shear stress impairs von Willebrand factor (VWF) and promotes abnormal bleeding in aortic stenosis. We sought to evaluate VWF impairment and its relationships to baseline or exercise obstruction in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Outflow obstruction was evaluated by rest and exercise echocardiography in 62 patients with HCM (age 44+/-16 years, 40 males). HCM was considered obstructive in 28 patients with rest or exercise peak gradient >or=30 mm Hg. Blood was sampled to assess VWF. History of bleeding was recorded. Baseline median (25th to 75th percentile) peak gradient was 11 (5-62) mm Hg. Shear-induced platelet adhesion was impaired in patients with obstructive HCM. The ratio of VWF-collagen-binding activity to antigen and the percentage of high-molecular-weight multimers of VWF were lower in patients with obstructive HCM than in those with nonobstructive HCM (0.49 [0.43 to 0.59] versus 0.82 [0.73 to 1.03] and 5.0% [3.9% to 7.2%] versus 11.7% [10.8% to 12.5%], respectively; both P<0.0001). Platelet adhesion time, VWF-collagen-binding activity-to-antigen ratio, and the percentage of high-molecular-weight multimers correlated closely and independently with peak gradient (r=0.81, r=-0.68, and r=-0.89, respectively; all P<0.0001). According to receiver operating characteristic curves, a peak gradient threshold of 15 mm Hg at rest and 35 mm Hg during exercise was sufficient to impair VWF. Conversely, VWF function tended to improve with a decrease in peak gradient. Obstructive HCM patients had a trend toward abnormal spontaneous bleeding. CONCLUSIONS: In obstructive HCM, VWF impairment is frequent and is closely and independently related to the magnitude of outflow obstruction. A resting peak gradient of 15 mm Hg is sufficient to impair VWF. VWF abnormalities might favor abnormal bleeding in this setting.

Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions.

OBJECTIVE: This study examines the incidence and factors associated with the failure of homograft valves and identifies those factors that are modifiable. METHODS: From 1990 to 2001, 96 homograft valves were implanted in the right ventricular outflow tract of 83 children (mean age 5.1 +/- 5.6 years). Clinical and blinded serial echocardiographic follow-up was performed on all 90 valves in the 77 survivors. RESULTS: Eighteen homograft valves were replaced as the result of pulmonary insufficiency (3), stenosis (9), or both (6). Freedom from reoperation was 71% at 9 years (95% confidence interval, 58%-84%). Forty-eight valves developed progressive pulmonary insufficiency of at least 2 grades, 26 valves developed transvalvular gradients of 50 mm Hg or greater, and 14 of these valves were also insufficient. The freedom from echocardiographic failure (progressive pulmonary insufficiency >or=2 grades or >or=50 mm Hg gradient) was only 27% at 5 years (95% confidence interval, 17%-37%). In a multivariate analysis (Cox regression), use of an aortic homograft (P =.001) and short antibiotic preservation time (P =.04) were associated with reoperation. Younger age (P =.01), ABO mismatch (P =.04), and diagnosis (P =.005) were associated with echocardiographic failure. In the subanalysis of patients with human leukocyte antigen typing, age (P =.002), aortic homograft (P =.04), and human leukocyte antigen-DR mismatch (P =.03) were associated with echocardiographic valve failure. CONCLUSION: Many homografts rapidly become insufficient and require replacement. In our analysis of both reoperation and echocardiographic failure, several immunologic factors are consistently associated with homograft failure. Matching for human leukocyte antigen-DR, blood group, and avoiding short preservation times (thus minimizing antigenicity) offers the potential to extend the life of these valves.

[Alcohol concentration in the coronary sinus after transarterial ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy]. / Die Alkoholkonzentration im Sinus coronarius nach transarterieller Ablation der Septumhypertrophie bei hypertropher obstruktiver Kardiomyopathie.

BACKGROUND AND OBJECTIVE: The size of the resulting myocardial necrosis varies after percutaneous transarterial ablation (PTA) of hypertrophied septum in patients with hypertrophic obstructive cardiomyopathy (HOCM). It was the aim of this study to discover whether the alcohol concentration in coronary sinus (CS) blood is a useful and appropriate parameter and what conclusions can be drawn from it. PATIENTS AND METHODS: PTA was done in four patients (two women and two men, aged 30-53 years) with HOCM. Before the intervention the gradient across the left ventricular outflow tract ranged form 20 to 80 mmHg, postextrasystolic it ranged from 40 to 180 mmHg. 1 x 2 ml ethanol was injected into the first septal branch in 3 patients, 2 x 2 ml in one. The alcohol concentration in coronary sinus blood was measured every 30 sec for up to 5 min before and after ablation. The amounts were compared with the size of the akinetic area in the echocardiogram and the maximal value of creatine kinase, as a measure of the size of myocardial necrosis. RESULTS: The left ventricular outflow gradient was reduced in all patients, to 0-30 mmHg and postextrasystolic to 30-90 mmHg. A pacemaker had to be implanted in one patient who developed a 3 degrees AV block. The alcohol concentration in coronary sinus blood ranged from maximally 1.53 and 0.23 per thousand after 30 sec and then fell to 0.56-0.12 per thousand after 5 min. The patient with the highest CS alcohol concentration also had the highest maximal value for creatine kinase (68 mumol/l) and the largest akinetic area in the echocardiogram. CONCLUSION: The extent of myocardial necrosis can probably be estimated from the CS blood concentration of alcohol after alcohol ablation. If, after the first injection, high alcohol concentrations are measured, further alcohol injections are not indicated.

Responses of plasma norepinephrine and heart rate during exercise in patients after Fontan operation and patients with residual right ventricular outflow tract obstruction after definitive reconstruction.

To determine the exercise responses of patients with congenital heart disease, 20 patients-5 who had undergone a right ventricular outflow tract reconstruction (group R; age, 15 +/- 2 years), eight who had undergone a Fontan operation (group F; age, 13 +/- 2 years), and seven who had a history of Kawasaki disease (group C; age, 15 +/- 1 years)-performed a treadmill exercise test. Patients of group R had a significant residual right ventricular outflow obstruction. Oxygen uptake (VO2), heart rate (HR), and plasma norepinephrine (NE) concentrations were measured at rest, during warm-up, at ventilatory threshold (VT), and at peak exercise. Exercise capacity was determined as a percentage of the predicted normal peak VO2 (%pVO2). The %pVO2 for groups R and F was 65 +/- 10 and 56 +/- 11, respectively. Peak HR for groups R and F was 171 +/- 4 and 155 +/- 5, which were lower than the HR for group C (p < 0.001). Although NE concentrations at rest, during warm-up, and at VT were significantly greater in groups R and F (p < 0.05), there were no significant differences in the NE concentrations at peak exercise. Peak HR correlated with %pVO2 (p < 0.001). The ratio of the increase in HR to NE from rest to VT was significantly lower in groups R and F than in group C (p < 0.001) and correlated with %pVO2 (r = 0.80; p < 0. 001). These data suggest that sympathetic nervous activity in groups R and F is increased at rest and during mild to moderate exercises, and reduced sinus node sensitivity to NE may be partly responsible for the abnormal HR response during exercise of patients with uncorrected congenital heart disease.

Effect of chronic left ventricular failure on beta-endorphin.

Stimulation of endogenous opiate secretion worsens circulatory dysfunction in several forms of shock, in part by inhibiting sympathetic activity. To investigate whether endogenous opiates have a similar effect in chronic heart failure (HF), we measured beta-endorphin concentrations and hemodynamic responses to naloxone infusion (2 mg/kg bolus + 2 mg.kg-1 x h-1) in six control (C) dogs and eight dogs with low-output HF produced by 3 wk of rapid ventricular pacing. The dogs with HF exhibited reduced arterial blood pressure (C, 123 +/- 4 vs. HF, 85 +/- 7 mmHg; P < 0.01) and cardiac outputs (C, 179 +/- 14 vs. HF, 76 +/- 2 ml.min-1 x kg-1; P < 0.01) and elevated plasma norepinephrine concentrations (C, 99 +/- 12 vs. HF, 996 +/- 178 pg/ml; P < 0.01) but normal beta-endorphin concentrations (C, 30 +/- 11 vs. HF, 34 +/- 12 pg/ml; P = NS). Naloxone produced similar transitory increases in blood pressure (C, 14 +/- 5 vs. HF, 26 +/- 25%) and cardiac output (C, 37 +/- 13 vs. HF, 22 +/- 15%) in both groups (both P = NS). No significant changes in norepinephrine concentration or systemic vascular resistance were observed in either group. These findings suggest that beta-endorphin secretion does not exacerbate circulatory dysfunction in chronic heart failure.

Variable arginine vasopressin levels in neonatal congestive heart failure.

Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 +/- 18 pg/ml, which was significantly greater than the mean control level (p less than 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 +/- 0.7 pg/ml, which was lower than the mean control level of 6 +/- 0.7 pg/ml (p less than 0.05). The data suggest that impaired forward flow to high pressure sinoaortic and ventricular baroreceptors is necessary for vasopressin release in congestive heart failure. In left ventricular outflow tract obstruction with heart failure these receptors may be impaired or absent, leading to decreased vasopressin release. Low plasma arginine vasopressin may adversely affect circulatory homeostasis.