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Cardiac function in the normal newborn: additional information by computer analysis of the M-mode echocardiogram.

Computer analysis of the M-mode echocardiogram in 50 normal newborns provided measurements of wall thicknesses and chamber size and, in addition, assessment of right and left ventricular wall, septal, and cavity dynamics throughout the cardiac cycle. Data obtained with this new technique indicated that (1) right and left ventricular cavity functions are similar in the normal newborn, (2) right and left ventricular cavity filling and emptying vary directly with peak rates of septal and ventricular wall thinning and thickening, respectively, and (3) there is a close time relationship among maximum left atrial dimension, minimum left ventricular dimension, and mitral valve opening. This analysis, which is the first complete analysis of the echocardiogram in the newborn, provides a normal range of septal and ventricular wall dynamics as well as right and left ventricular and left atrial function and has clinical implications in that it may allow early recognition of both congenital and perinatal myocardial disease.

Atrial Function↗

[Diastolic function of the left ventricle and congestive heart failure with normal systolic function].

Mechanical performance of the heart depends on the physiologic interplay of its systolic and diastolic function. However, the cardiologist is used to defining left ventricular (LV) function only in terms of ejection fraction, cardiac output and blood pressure, thus observing only systolic function. In the last 10 to 15 years experience has revealed that, despite the presence of a normal LV systolic function, alterations of LV diastolic function may impair exercise tolerance and may be responsible for the clinical picture of about 30% of patients with a definite diagnosis of congestive heart failure. Doppler echocardiography has emerged as the most feasible and accurate noninvasive technique in assessing LV diastolic function in the clinical setting. Combined Doppler evaluation of transmitral and pulmonary venous flow velocity recordings, by transthoracic approach, allows us to obtain clinically relevant information on LV relaxation, LV filling, LV compliance, and LV end-diastolic and mean filling pressure, as well as on left atrial function, in more than 95% of patients referred to the echo-lab. With this combined evaluation different types of filling patterns have been identified. Clinical evaluation, together with structural/functional information obtained by M-mode and two-dimensional echocardiography, and mainly with detailed analysis of these LV filling patterns by Doppler, allow for a fairly accurate identification of various diastolic abnormalities, as well as the presence of diastolic dysfunction, i.e., increased filling pressures. Diastolic failure, characterized by the association of diastolic dysfunction and symptoms of pulmonary venous congestion, can now be more precisely identified following the criteria established by the Working Group on Diastolic Heart Failure of the European Society of Cardiology. Echo-Doppler age-adjusted normal values of indices of impaired LV relaxation and filling, along with cut-off values of Doppler signs of reduced compliance or increased filling pressures have been defined by the Working Group, and are herewith reported for practical purposes. Furthermore, as a reference for an advanced echo-lab, a "decalogue" of diastological performances is suggested.

Diastole↗

RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient versus strict rate control in patients with and without heart failure. Background, aims, and design of RACE II.

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown. OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs. METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups. RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years. CONCLUSION: This study should provide data how to treat patients with permanent AF.

Anti-Arrhythmia Agents↗

Normal left ventricular systolic function in adults with atrial septal defect and left heart failure.

Systolic left ventricular contractile function has not been extensively evaluated in patients with atrial septal defect who have symptoms of left-sided congestive heart failure. This study examined left ventricular systolic function hemodynamically and angiographically in 6 such adult patients (Group A), 12 adult patients with atrial septal defect without heart failure (Group B) and 20 normal subjects. The mean ( +/- standard error of the mean) left ventricular end-diastolic pressure was higher in patients in Group A (17 +/- 0.8 mm Hg) than in patients in group B (6.9 +/- 0.6 mm Hg) (p less than 0.001). Both right atrial pressure ( 11 +/- 1.3 versus 4.9 +/- 0.5 mm Hg) (p less than 0.001) and mean pulmonary arterial pressure (30 +/- 1.8 versus 15 +/- 1 mm Hg) were also higher in Group A than in Group B. Left ventricular cardiac index and stroke work index did not differ in the two groups. Variables of left ventricular systolic function were similar in both groups of patients and in normal subjects: Ejection fraction was 0.71 +/- 0.05 in Group A, 0.74 +/- 0.02 in Group B and 0.74 +/- 0.01 in normal subjects. Velocity of circumferential shortening was 1.38 +/- 0.14 circumferences/s in Group A, 1.38 +/- 0.07 circumferences/s in Group B and 1.27 +/-0.04 circumferences/s in normal subjects. There was no difference in left ventricular contractile function as indicated by the ratio of end-systolic wall stress to end-systolic volume index among the three groups: normal subjects, average 5.6 +/- 0.19 versus 6.1 +/- 0.5 in Group B and 6.0 +/- 0.6 dynes X 10(3)/cm(2)/(ml/m(2) in Group A. This study of patients with atrial septal defect and left heart failure indicates that abnormal left ventricular systolic contractile function is probably not the cause of the symptoms and elevated left heart filling pressures observed in this group. An abnormality in left ventricular diastolic filling, perhaps related to the volume loaded right ventricle, may explain these changes.

Adolescent↗

Relationship between left ventricular diastolic function and atrial natriuretic factor in never-treated mild hypertensives.

Using digitized M-mode echocardiograms, we evaluated the relationship between plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal renal function. For each subject we collected a blood sample for plasma ANF evaluation and, immediately after, we recorded the LV echocardiogram. All the patients had normal LV diastolic diameter and systolic function; LV hypertrophy was present in 10 patients, 7 of whom had left atrial enlargement, and 13 patients had impaired LV diastolic function. ANF was similar between patients with and without LV hypertrophy, as well as between patients with and without left atrial enlargement, whereas ANF was significantly (P < .01) higher in patients with LV diastolic dysfunction than in patients with normal diastolic function. ANF was inversely correlated with both indices of diastolic function (peak lengthening rate and peak wall thinning rate), whereas it did not correlate with blood pressure, heart rate, end-systolic wall stress, and other LV parameters. In conclusion, from our results, ANF level in never-treated mild hypertensives is related neither to the degree of LV hypertrophy nor to the afterload, expressed as blood pressure or end-systolic wall stress, whereas it is mainly influenced by LV diastolic function: the diastolic impairment induces an increase in ANF level, probably through an increased atrial stretch.

Adult↗

Clinical utility and management impact of M-mode echocardiography.

To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.

Echocardiography↗

Development of a new animal model of chronic mitral regurgitation in rats under transesophageal echocardiographic guidance.

Large animal models (dog and sheep) are often used for the investigation of the pathophysiology of chronic mitral regurgitation (MR). A major limitation of large animal models is cost. The aim of this study was to develop a new animal model of chronic MR. Left thoracotomy was performed in 34 rats. Under the guidance of transesophageal echocardiography, a fine needle was inserted into the left ventricle (LV) to damage the mitral leaflets and produce MR. Serial transthoracic echocardiography was performed to assess LV remodeling and function. Left atrial and LV diameters were significantly larger, and LV fractional shortening was lower in the MR group than in the sham group. The 150-day survival was 59% in the MR group and 100% in the sham group (P < .01). This new animal model of chronic MR may be used in the study of the pathophysiology of chronic MR and pharmacologic therapies.

Animals↗

Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter.

The need for prophylactic anticoagulation to prevent embolism before direct current cardioversion is performed for atrial fibrillation or atrial flutter is controversial. To examine this issue further, a retrospective review was undertaken to assess the incidence of embolic complications after cardioversion. The review involved 454 elective direct current cardioversions performed for atrial fibrillation or atrial flutter over a 7 year period. The incidence rate of embolic complications was 1.32% (six patients); the complications ranged from minor visual disturbances to a fatal cerebrovascular event. All six patients had atrial fibrillation, and none had been on anticoagulant therapy (p = 0.026). The duration of atrial fibrillation was less than 1 week in five of the six patients who had embolic complications. Baseline characteristics of patients with a postcardioversion embolic event are compared with those of patients who did not have an embolic event. There was no difference in the prevalence of hypertension, diabetes mellitus or prior stroke between the two groups, and there was no difference in the number of patients who were postoperative or had poor left ventricular function. Left atrial size was similar between the two groups. No patient in the embolic group had valvular disease. No patient with atrial flutter had an embolic event regardless of anticoagulant status; therefore, anticoagulation is not recommended for patients with atrial flutter undergoing cardioversion. Prophylactic anticoagulation is pivotal in patients undergoing elective direct current cardioversion for atrial fibrillation, even those with atrial fibrillation of less than 1 week's duration.

Anticoagulants↗

Measurement of funny current (I(f)) channel mRNA in human atrial tissue: correlation with left atrial filling pressure and atrial fibrillation.

INTRODUCTION: The funny current (I(f)) contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced I(f) activity in myocardial tissue may lead to increased automaticity and therefore tachyarrhythmia. We measured the amount of I(f) activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF). METHODS AND RESULTS: A total of 34 patients undergoing open heart surgery were included (15 men and 19 women, aged 55+/-10 years). Atrial tissue was obtained from the right atrial free wall, the right atrial appendage, the left atrial free wall, and the left atrial appendage, respectively. The mRNA amount of the I(f) channel was measured by reverse transcription polymerase chain reaction and was normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. We found that the I(f) channel mRNA was present at all the atrial sampling sites. A higher left atrial filling pressure, an indicator of congestive heart failure, was associated with a higher I(f) mRNA level (r2 = 0.446, P < 0.01 by linear regression). We also found that the mRNA amount was significantly higher in patients with AF than in patients without AF (1.68+/-0.49 vs 1.27+/-0.43; P < 0.05). Age, sex, right atrial filling pressure, left atrial dimension, and left ventricular ejection fraction had no significant effect on the mRNA level. CONCLUSION: The mRNA of the I(f) channel is present in the free-wall area and appendage area from both atria. Increased left atrial filling pressure and clinical AF are associated with increased I(f) mRNA level.

Adolescent↗

Effect of pacing on epinephrine-stimulated atrial natriuretic factor release.

Previous in vitro studies showed that epinephrine stimulation can induce atrial natriuretic factor (ANF) release only form the right atrium but not from the left. In addition, sinus node has been shown to play an important role in the release of ANF. In vitro studies were done in isolated left and right rat atria to determine if pacing can induce the left atria to release ANF during epinephrine stimulation. ANF concentrations in the perfusate were measured by a radioimmunoassay method. Epinephrine increased ANF release in the right atria (from 6.3 +/- 0.8 to 10.8 +/- 0.9 pg/min/mg), but not in the unpaced left atria (4.2 +/- 0.4 and 4.2 +/- 0.3 pg/min/mg). However, when the atria were paced, ANF release rose in both the left (from 6.2 +/- 0.5 to 11.5 +/- 1.4 pg/min/mg) and right (from 8.4 +/- 1.15 to 16.6 +/- 1.8 pg/min/mg) atria with epinephrine addition. These results suggest that atrial contraction and tension play an important role in epinephrine-stimulated ANF release.

Animals↗

Early recurrence of atrial fibrillation after external cardioversion.

UNLABELLED: Early recurrence of atrial fibrillation (AF) has been reported to occur in a significant number of patients after internal cardioversion. However, information about early recurrence of AF after external cardioversion has never been reported. The present study was conducted to investigate the clinical and electrophysiological characteristics of early recurrence of AF and its role in failure of cardioversion in patients with chronic AF. METHODS AND RESULTS: The study included 50 consecutive patients, age 69+/-9, with a history of chronic AF for more than 3 months duration and electrical cardioversion. They were divided into two groups according to the presence (group 1) or absence (group 2) of early recurrence of AF. There were 13 (26%) patients in group 1 and 37 (74%) patients in group 2. The age, gender, duration of AF, left ventricular function, left atrial dimension, and underlying heart disease were similar between group 1 and 2. Forty-five patients were successfully converted to sinus rhythm with a mean energy of 158+/-57 . Among those who failed to be converted to sinus rhythm, 4 (80%) belonged to group 1 and 1 (20%) belonged to group 2. The early recurrences of AF were initiated with consecutive APDs; but the numbers of APD in the first 30 seconds after cardioversion were similar between group 1 and 2. However, the coupling interval of the second APD was shorter in group 1 than group 2 (188+/-22 vs 324+/-59 ms, P = 0.003). Nine of the 13 early recurrences were prevented by an increase of shock energy (n = 3) or intravenous amiodarone infusion (n = 6). There were no differences in duration of follow-up, recurrence rate, and time interval to recurrence between group 1 and group 2. Early recurrence of AF occurred in 26% of chronic AF patients who underwent external electrical cardioversion and was a major cause of failure in cardioversion. Early recurrence of AF was initiated by APDs with decreasing coupling intervals and could be prevented with an increase of shock energy or amiodarone.

Aged↗

Diastolic dysfunction and heart failure: causes and treatment options.

Diastolic dysfunction is the underlying problem in one third of patients with heart failure, but it is still not well understood. Carefully excluding other causes of heart failure and recognizing indicators of diastolic dysfunction on invasive and noninvasive tests are important in establishing the diagnosis and in guiding therapy. Left ventricular relaxation and stiffness and left atrial function are the most important factors acting together to maintain adequate cardiac output under normal filling pressure. Echocardiography is the most important tool for the diagnosis of diastolic heart dysfunction. It is portable, safe, and excludes other causes of heart failure, such as valvular disease. Diuretics can be used to reduce volume overload, but caution is advised, as aggressive diuresis decreases stroke volume more in diastolic dysfunction than in systolic dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target.

Atrial fibrillation and hypertension are 2 prevalent, and often coexistent, conditions in the North American population. Their incidence increases with advancing age, and they are responsible for considerable morbidity and mortality. Although the relation between the 2 conditions has long been known, the treatment of hypertension is not currently a focus in the clinical management of atrial fibrillation. Hypertension is associated with left ventricular hypertrophy, impaired ventricular filling, left atrial enlargement, and slowing of atrial conduction velocity. These changes in cardiac structure and physiology favor the development of atrial fibrillation, and they increase the risk of thromboembolic complications. Conventional therapy of atrial fibrillation has focused on interventions to control heart rate and rhythm and the prevention of stroke through the use of anticoagulant medications. In patients with atrial fibrillation, aggressive treatment of hypertension may reverse the structural changes in the heart, reduce thromboembolic complications, and retard or prevent the occurrence of atrial fibrillation. Specific pharmacotherapy could potentially play a major role in the primary and secondary prevention of atrial fibrillation and its complications.

Antihypertensive Agents↗

Left atrial appendage dysfunction in chronic nonvalvular atrial fibrillation is significantly associated with an elevated level of brain natriuretic peptide and a prothrombotic state.

The study tested the hypothesis that left atrial appendage (LAA) dysfunction in nonvalvular atrial fibrillation (NVAF) correlates with a prothrombotic state, and investigated whether the plasma natriuretic peptides are marker of LAA dysfunction in NVAF. Sixty-seven patients underwent transthoracic and transesophageal echocardiography. The left ventricular fractional shortening, left atrial diameter (LAD), LAA flow velocity and the grade of spontaneous echo contrast (SEC) were determined. The plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), D-dimer, and thrombin-antithrombin III complex (TAT) were measured. The patients were divided into 2 groups according to LAA flow velocity: group I (LAA velocity <20 cm/s) and group II (LAA velocity > or = 20cm/s). The SEC score, D-dimer, TAT, BNP and LAD were significantly increased in group I. Based on simple linear regression analysis, SEC score (r=-0.638), LAD (r=-0.493), D-dimer (r = -0.485), BNP (r = -0.463), TAT (r = -0.455) and age (r = -0.314) were inversely correlated with LAA flow velocity. Multivariate analysis showed that SEC score (p = 0.0014) and plasma BNP level (p=0.0075) were independent negative predictors for LAA flow velocity. In conclusion, LAA dysfunction is associated with a prothrombotic state, and the plasma BNP concentration may serve as a determinant of LAA function in NVAF.

Aged↗

Plasma atrial natriuretic factor during ethanol ingestion in volume-loaded subjects.

The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects.

Adult↗

Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy.

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Synergistic regulation of ANF in isolated rat hearts.

The interaction between cardiac sympathetic stimulation of atrial natriuretic factors (ANF) release and left atrial stretch was examined in groups (n = 5 or 6) of isolated, perfused (10 ml/min), paced rat hearts. Left atrial stretch, produced by an increase in atrial pressure of 1.1 +/- 0.2 mmHg over 8 min, transiently (4 min) increased ANF release by 46 +/- 4% over baseline (220 pg/ml buffer; P < 0.05). Infusion of 1 microM norepinephrine (NE) over 28 min caused a sustained increase in ANF release of 76 +/- 10% (P < 0.05). Atrial stretch plus NE caused additive effects on ANF release during stretch but 2.4 times the additive effects after stretch (P < 0.05). To examine whether resting tension modulates the ANF response to sympathetic stimulation, the left atrium was stretched throughout the experiment by increasing the atrial pressure by 1-1.5 mmHg. Infusion of 1 microM NE over 28 min increased ANF release by 216 +/- 46% (P < 0.01) in the prestretched heart, compared with a calculated summed increase of 85% due to NE alone plus prestretch alone. Infusion of 0.5 microM veratridine, known to stimulate ANF via mechanical effects on the heart, increased ANF release by 88 +/- 3% (P < 0.01). Scorpion venom, known to dose dependently stimulate ANF secretion via activation of neuronal sodium channels, elicits a negligible increase in ANF release at the threshold concentration of 0.1 microM. The combined infusion of 0.5 microM veratridine plus 0.1 microM venom increased ANF release by 239 +/- 53% (n = 6, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clearance receptors and endopeptidase: equal role in natriuretic peptide metabolism in heart failure.

The effects of separate and combined endopeptidase inhibition (by SCH-32615) and natriuretic peptide receptor C blockade [by C-ANP-(4-23)] on the clearance and bioactivity of atrial (ANP) and brain (BNP) natriuretic peptides was investigated in eight sheep with heart failure. SCH-32615 and C-ANP-(4-23) administered separately induced significant and proportionate dose-dependent rises in plasma ANP, BNP, and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Associated with these changes were reductions in arterial pressure, left atrial pressure, and peripheral resistance and increases in cardiac output, urine volume, sodium excretion, and creatinine clearance. SCH-32615 induced greater diuresis and natriuresis than C-ANP-(4-23). Combined administration of SCH-32615 and C-ANP-(4-23) induced greater than additive rises in plasma ANP, BNP, and cGMP concentrations, with enhanced hemodynamic effects, diuresis, and natriuresis and reduced plasma aldosterone levels. In conclusion, we find that the enzymatic and receptor clearance pathways contribute equally to the metabolism of endogenous ANP and BNP in sheep with heart failure. Combined inhibition of both degradative pathways was associated with enhanced hormonal, hemodynamic, and renal effects and may have greater potential therapeutic value than either agent separately.

Aldosterone↗