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Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after
D B Northridge1, A Jardine, E Henderson
1Department of Cardiology, Western Infirmary, Glasgow.
Insights
Candoxatrilat increased atrial natriuretic factor (ANF) levels in heart failure patients, reducing preload without improving left ventricular function. The effects were attributed to peripheral mechanisms, not central cardiac improvements.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Heart failure is characterized by impaired cardiac function and neurohormonal imbalances.
- Atrial natriuretic factor (ANF) plays a crucial role in cardiovascular homeostasis.
- Understanding the mechanisms behind ANF-mediated effects is vital for developing effective treatments.
Purpose of the Study:
- To investigate the hemodynamic and functional effects of increasing atrial natriuretic factor (ANF) concentrations using candoxatrilat in patients with mild heart failure.
- To determine whether the observed effects are mediated by central (cardiac) or peripheral mechanisms.
Main Methods:
- A randomized, single-blind, placebo-controlled study involving six male patients with mild heart failure (NYHA class II).
- Patients received intravenous doses of candoxatrilat or placebo over four consecutive days.
- Measurements included plasma ANF concentrations, hemodynamic indices (pressures, cardiac output), and left ventricular diastolic function (Doppler echocardiography E:A ratio).
Main Results:
- Candoxatrilat significantly increased plasma ANF concentrations threefold compared to placebo.
- A significant reduction in right atrial pressure and pulmonary artery wedge pressure was observed.
- Left ventricular diastolic function, assessed by the E:A ratio, significantly decreased, indicating impaired filling, while systolic function showed no improvement.
Conclusions:
- Candoxatrilat effectively raises plasma ANF levels and reduces preload in heart failure patients.
- The observed reduction in preload is likely due to peripheral mechanisms, such as increased venous capacitance or reduced blood volume.
- No evidence suggests an improvement in left ventricular systolic or diastolic function, indicating that the benefits are not centrally mediated through direct cardiac enhancement.
Objective:
+/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects.
Design:
This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days.
Setting:
A teaching hospital department of cardiology.
Patients:
Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg.
Main Outcome Measures:
Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo.
Results:
+/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05).
Conclusions:
+/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.