Atrial natriuretic peptide secretion in mitral stenosis

396

BRIEF

REPORTS

artery wedge pressure. Blood samples were drawn from pulmonary artery through a catheter into icechilled plastic tubes containing ethylenediamine tetraacetic acid (1 mg/ml) and aprotinin (500 kIU/ml), immediately separated and stored frozen at -2OOC. Plasma ANP was extracted from a 2-mI aliquot plasma on a Cl8 octadecylsilane cartridge (Sep-Pak, Waters Associates) and measured by a specific radioimmunoassay as described elsewhere.3 Cardiac catheterization and ventriculography confirmed that all patients had pure or mixed MS (Table I). Although plasma ANP levels in the pulmonary artery varied from 58 to 1,450 pg/ml (mean 357 f 381, mean f standard deviation), they were positively correlated with the pressure gradient across the mitral valve (r = 0.80, p 0.05).

Atrial Natriuretic Peptide Secretion in Mitral Stenosis HIROKI YOSHIMI, MD ICHIRO INOUE,MD YUKIO HIRATA, MD SHUNICHI KOJIMA, MD MORIO KURAMOCHI, MD KEIICHI ITO, MD HIROSHI SAKAKIBARA, MD TERUO OMAE, MD

A

ccumulating evidence implies that atria1 pressure and distention has a primary role in regulating atria1 natriuretic peptide (ANP) secretion from the heart.Q To clarify the contribution of left atria1 pressure on secretion of human ANP, we studied the relation between plasma immunoreactive ANP levels and hemodynamic function in patients with mitral stenosis (MS]. Patients with suspected MS (6 men, 24 women], aged 35 to 64 years (mean 48 f 9), underwent rightand left-sided cardiac catheterization. Each patient gave informed consent. All medications were withheld before the study. Pressures in the right atrium, pulmonary artery and pulmonary artery wedge position were measured. Pressure gradient across the mitral valve was calculated by subtracting left ventricular end-diastolic pressure from mean pulmonary From the Department of Medicine, National Cardiovascular Center Hospital and Research Institute, Suita, Osaka 565, Japan. Manuscript received February 3, 1987; revised manuscript received and accepted April 2, 1987. _

TABLE

I

Clinical

and Hemodynamic

Data

Age W Case

8 Sex

Diagnosis

1 2 3 4 5 6 7 0 9 10 11 12 13 14 15 16 17 18 19 20

35M 35F 36F 38F 40F 41M 41M 42M 42F 46M 46F 52M 52F 55F 56F 56F 59F 59F 62F 64F

MS, MS MS MS, MS, MS, MS, MS MS MS MS, MS, MS MS MS MS, MS, MS, MS MS

AR = aortic mean pulmonary

regurgitation; AS = aortic artery pressure; PAWP

Although it is not established that all atria1 blood drains into the coronary sinus because a small proportion of left atria1 blood and a larger proportion of right atria1 blood also drain through the thebesian veins, recent study has shown that ANP is largely secreted into the coronary sinus.4 In the present study, plasma ANP levels in the pulmonary artery from patients with MS were found to be closely correlated with the pressure gradient across the mitral valve, mean pulmonary artery wedge pressure and pulmonary artery pressure, whereas no correlation was observed between ANP levels and mean right atria1 pressure. Our data are consistent with a previous report5 in which levels of plasma ANP in the right ventricle of patients with isolated left ventricular failure did not parallel those of

AR

AR AR AR AR

AR AS

AR AR AS

stenosis; = mean

RAP

PAP

PAWP

(mm W

(mm W

(mm Hg)

35 45 31 22 37 15 14 14 II 15 36 17 17 9 17 18 14 25 25 20

12 23 17 17 28 8 5 6 7 10 26 9 10 4 10 11 5 15 15 12

4 0 2 7 4 1 4 2 2 4 1 4 2 0 2 3 0 3 3 4 LVEDP = left ventricular pulmonary artery wedge

end-diastolic pressure; pressure: RAP = mean

PAWP-LVEDP

MR = mitral regurgitation: right atrial pressure.

ANP

(mm Hg)

@@ml)

8 18 13 4 25 5 5 4 3 5 21 6 5 5 7 4 4 IO 9 6 MS = mitral

67 1,110 862 95 647 50 134 301 105 92 1,450 465 210 285 430 160 139 194 129 210 stenosis:

PAP =

August

THE

AMERICAN

gz m E Iq E>

F E

x 5 b 5 g 1

25

0

Relation of Sudden Death in Pure Mitral Regurgitation, With and Without Mitral Valve Prolapse, to Repetitive Ventricular Arrhythmias and Right and left Ventricular Ejection Fractions PAUL KLIGFIELD, MD GLARE HOCHREITER, MD NATHANIEL NILES, MD RICHARD B. DEVEREUX, MD JEFFREY S. BORER, MD

C

omplex ventricular arrhythmias are common in patients with mitral regurgitation [MR), with and without mitral valve prolapse (MVP), and short-term mortality From the Division of Cardiology, Department of Medicine, The New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, New York 10021. This study was supported by Grant ROl-HL-26504 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received November and accepted

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1. Lang RE, Thiilken H, Ganten D, Luft FC, Ruscoaho H, Unger T. Atriof natriuretic factor: a circulating hormone stimulated by volume loading. Nature 1985;314:264-266.

received

60

10

of right atria1 pressure. These data strongly suggest that elevation of left atria1 pressure resulting from MS is the predominant stimulus for ANP secretion. Therefore, measurement of plasma ANP levels in pulmonary artery should provide more reliable information in evaluating the severity of MS.

manuscript

Volume

Z 7 ! 5

ANP bg/ml)

revised

OF CARDIOLOGY

20

c;& r? 9s HG

12,1986; 1987.

JOURNAL

30

2 k5

FIGURE 1. Correlations of plasma ANP levels in pulmonary artery with pressure gradient across mitral valve (mean pulmonary artery wedge pressure minus left ventricular end-diastolic pressure), mean pulmonary artery wedge pressure, mean pulmonary artery pressure, and mean right atrial pressure in patients with mitral stenosis.

I, 1987

February

27,

ANP bg/mO

2. Rodeheffer RJ, Tanaka I, Imada T. Hollister AS, Robertson D, Inagami T. Atrial pressure and secretion of atrial natriuretic factor into the human central circulation. [ACC 1986;8:18-26. 3. Kojima T, Hirata Y, Fukuda Y, Iwase S, Kobayashi Y. Plasma atrial natriuretic peptide and spontaneous diuresis in sick newborn infants. Arch Child Dis [in press]. 4. Sugawara A, Nakao K, Morita N, Suds M, Shimakura M, Kiso Y, Yamori Y, Nishimura K, Soneda 1, Imura H. a-human atrial natriuretic polypeptide is released from the heart and circulates in the body. Biochem Biophys Res Commun 1985;129:439-446. 5. Bates ER, Shenker Y, Grekin RJ. The relationship between plasma levels of immunoreactive atria1 natriuretic hormone and hemodynamic function in man. Circulation 1986;73:1155-1161.

is high in unoperated patients with MR who have depressed right ventricular (RV) or left ventricular (LVJ ejection fractions (EF) at rest.lJ Death in these patients may result either from severe hemodynamic failure or from a sudden arrhythmic event,3 as occurs in other forms of heart disease.4-6 The hypothesis that arrhythmic death occurs in MR is supported by few previous observations beyond observed mortality in medically treated patients217 and arrhythmia-related postoperative mortality in patients undergoing mitral valve replacement.* However, recognition of primary valvular disease among a small subset of survivors of cardiac arrestgJO suggests that arrhythmias in MR are not necessarily benign. In addition, sudden death has been associated with MVPll and occurs more often in MVP patients with hemodynamically important MF$12J3 Because MVP is emerging as the most common cause of severe MR,14 and because arrhythmia complexity in MR appears to be independent of etiology,l the present study was undertaken to examine the relation of repetitive ventricular arrhythmias to the likelihood of death and to the mode of death in unoperated patients with MR with or without MVP. Among a prospectiveIy studied cohort of patients with regurgitant valvular disease,2 31 unoperated patients with hemodynamically important MR were followed for a mean period of 27 months. There were 16 men and 15 women, mean age 49 years. Selection