Atrial Natriuretic Peptide, Aldosterone, and Plasma Renin Activity in Peripartum Heart Failure Br Heart J: First Published As 10.1136/Hrt.65.3.152 on 1 March 1991

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152 Br Heart J 1991;65:152-4 Atrial natriuretic peptide, aldosterone, and plasma renin activity in peripartum heart failure Br Heart J: first published as 10.1136/hrt.65.3.152 on 1 March 1991. Downloaded from

C 0 Adesanya, F I Anjorin, I A Sada, E H 0 Parry, G A Sagnella, G A MacGregor

Abstract Patients and methods Plasma concentrations of atrial We studied seven patients (mean age 28; range natriuretic peptide and aldosterone and 21-30 years) with peripartum heart failure. plasma renin activity were measured in All the patients and controls had carried out patients with peripartum heart failure the postpartum rituals of body heating. In and in age matched healthy women post addition to the estimated daily salt intake of partum. Both groups had carried out approximately 10 g, all but one patient (case traditional postpartum practices of salt 6) had ingested large quantities of Kanwa, a consumption and body heating. Plasma lake salt. The traditional dose of Kanwa is concentrations (mean (SEM)) of atrial approximately 30 g/day. This has been natriuretic peptide were significantly estimated to contain 450 mmol of sodium. higher in the seven patients with Kanwa is taken in pap with large amounts of peripartum heart failure (146-9 (24 3) pg/ water daily for 40 days or more. The patients ml) than in the seven controls (4 4 (08) were admitted to hospital and their symptoms pglml). Both plasma aldosterone and and signs were recorded. Particular attention plasma renin activity were suppressed in was paid to the examination of the cardio- the patients with peripartum heart vascular system. Blood pressure, pulse, failure. After treatment for the heart jugular venous pressure, and the precordium failure plasma atrial natriuretic peptide were carefully examined. The measurement of fell considerably and there were jugular venous pressure was used as an indica- associated increases in plasma aldo- tion of central venous pressure. It was sterone and plasma renin activity. measured with the patients semi-sitting at an The high plasma concentrations of angle of 30 or 45° with the head turned to the atrial natriuretic peptide may have been left. The patients were weighed and before

a compensatory response to salt and treatment routine investigations (chest x ray, http://heart.bmj.com/ water retention as well as to the heart electrocardiogram, full blood count, urea and failure. These high concentrations could electrolytes, serum proteins, urine analysis, also, in part, have suppressed the release and spot urine sodium) were performed. ofaldosterone and renin in an attempt to Treatment was started before a 24 h urine correct for volume overload. sample was collected for the measurement of sodium. Atrial natriuretic peptide (a ANP), aldosterone, and plasma renin activity were

Women in and around Zaria in northem measured before treatment and up to seven on September 29, 2021 by guest. Protected copyright. Nigeria who develop peripartum heart failure days after treatment with digoxin, frusemide, have customarily eaten large quantities of lake and salt restriction. Except for chest x rays, salt (Kanwa) and water in the early post- the controls also had similar routine inves- partum period.' They are also likely to have tigations and hormone assays. Department of performed the ritual of body heating. Both of Medicine, Ahmadu these practices can increase blood volume and BLOOD COLLECTION Bello University have been associated with high output cardiac Venous blood was collected at noon with the Hospital, Zaria, Nigeria failure.2 These women have no evidence of woman in the semi-sitting (cardiac) position. C O Adesanya underlying cardiac or renal disease. Besides The samples were collected into EDTA tubes F I Anjorin the volume expansion, the pressure load of to measure plasma renin activity; in heparin I A Sada postpartum hypertension may also contribute tubes for aldosterone, and into EDTA tubes Wellcome Tropical to the cardiac damage in susceptible indi- plus 15 MI of trasylol solution (5000 KIU/ml; Institute, London viduals. So far the role of the kidney's ability E H 0 Parry Bayer, Aprotinin) to measure atrial natriuretic load in heart Blood Pressure Unit, in handling the salt peripartum peptide. Similar methods were used to analyse Department of failure has not been determined. Several fac- blood samples collected after treatment. The Medicine, St George's tors are important in the control of renal blood samples were immediately centrifuged Hospital Medical sodium in the renin- School, London excretion, particular at 4'C and the plasma was stored in clear G A Sagnella angiotensin-aldosterone system and the newly plastic tubes at -20°C. Plasma samples for G A MacGregor discovered atrial natriuretic peptides. Little is renin were preserved in EDTA tubes; those Correspondence to known. about these hormonal determinants in for aldosterone and atrial natriuretic peptide Professor C 0 Adesanya, heart failure. In the present were in clear tubes. All Departnent of Medicine, peripartum study placed plastic samples Ahmadu Bello University we measured circulating concentrations of for hormone measurements were stored at Hospital, atrial natriuretic and aldosterone and were in the Zaria, Nigeria. peptide, -20'C until they transported, renin in women before and after atrial Accepted for publication activity frozen state, to London, where plasma 4 December 1990 treatment for peripartum heart failure. natriuretic peptide, aldosterone, and plasma Atrial natriuretic peptide, aldosterone, andplasma renin activity in peripartum heartfailure 153

renin activity were measured by radio- normal range. The patients had cardiomegaly immunoassay as described elsewhere.3 on chest x ray and the electrocardiogram We used paired or unpaired tests as showed sinus tachycardia and non-specific ST appropriate for group comparisons. Non- changes. The patients responded promptly to

parametric tests were used for urinary sodium treatment with an average weight loss of 12 Br Heart J: first published as 10.1136/hrt.65.3.152 on 1 March 1991. Downloaded from and plasma hormone measurements because (08) kg (admission weight 58 (1-7), discharge of considerable differences in sample variances weight 46 (1-1) kg) and the disappearance of and also because of uncertainty about the peripheral oedema. Dyspnoea and other symp- form of the distribution for these toms subsided as the jugular venous pressure measurements in the patient group. A p value fell to normal, implying a reduction in the of < 005 was regarded as statistically extracellular fluid volume and in pulmonary significant. Results are given as means (SEM). venous congestion. Table 3 shows the plasma concentrations of Results atrial natriuretic peptide, aldosterone, and All controls had normal physical findings, were renin before treatment in the patients with normotensive, and had normal cardiograms. peripartum cardiac failure and the controls. All the patients with peripartum heart failure Plasma concentrations of atrial natriuretic were in gross congestive heart failure (class IV, peptide were significantly higher (146-9 (24 3) New York Heart Association criteria). Tables 1 pg/ml) in the women with peripartum heart and 2 summarise the clinical data. The patient failure than in the controls (4 4 (08) pg/ml). group had slightly raised blood pressure on After treatment for the heart failure plasma admission (table 1). This was transient and not atrial natriuretic peptide fell considerably consistent with systemic hypertension. (figure). Before treatmentplasma aldosterone in Fundoscopic findings in these patients were the patients was significantly lower than in the also normal. In both the patients and controls controls (table 3), as was plasma renin activity a full blood count, urine analysis, urea, electro- but not significantly (table 3). In the controls, lytes, and serum proteins were all within the plasma renin activity ranged from 0 12 to 3-56 ng/ml/h, but one woman had a much higher Table I Clinical data (mean (SEM)) on patients with value (17.93 ng/ml/h). There was no apparent peripartum heartfailure and on healthy puerperal women reason for this. After treatment for heart failure both plasma aldosterone and plasma renin Heart activity increased significantly in the women. Controls failure p value Variable (n=7) (n=7) Age (yr) 28 (1-5) 28 (1-5) NS Last delivery (mnth) 3 (0.7) 3 (0 7) NS Parity 5 (0-4) 6 (0-7) NS 200- Women with peripartum heart failure Duration of symptoms (mnth) - 1-4 (0.4) - http://heart.bmj.com/ Systolic blood pressure 150- Treatment (mm Hg) 120 (3.8) 140 (9 8) NS I Diastolic blood pressure * (mmHg) 86 (3-0) 107 (4-5) < 0-01 ANP (pg/ml) 100- Heart rate (beats/min) 85 (4-1) 108 (4-5) < 001 JVP (cm) - 7 (0-7) - 50- JVP, jugular venous pressure.

Table 2 Laboratory data (mean (SEM)) on controls on September 29, 2021 by guest. Protected copyright. and women with peripartum heartfailure

Heart Controls failure p value (n=7) (n=7) PRA (ng/ml/h) Packed cell volume (%) 40 (1-9) 38 (1 9) NS Spot urinary sodium* (mmol/l) 188 (18 5) 89 (1-5) < 0-05 Serum albumin (g/l) 43 (1 9) 37 (1-5) NS Cardiothoracic ratio - 0 64 (0 03) - 1000- *Treatmnent started before the 24 hour urine collection was * completed. 800- 600- Table 3 Plasma atrial natriuretic peptide, aldosterone, Aldosterone andplasma renin activity in healthy puerperal women (pmol/l) and in patients with peripartum heartfailure (before 400- treatment) 200- Heart Controls failure p value* Controlsl 0 3 (n=7) (n=7) Days Plasma ANP (pg/ml) 4 4 (0 8) 146-9 (24-3) < 0-01 Plasma aldosterone Plasma concentrations of atrial natriuretic peptide (pmol/l) 139-0 (15-1) 85-6 (13-7) < 0-05 (ANP), aldosterone, and plasma renin activity (PRA) PRA (ng/ml/h) 3-4 (2-4) 0-43 (0-24) NS in seven healthy women post partum and in seven patients with postpartum heartfailure before (day 0) and after *Non-parametric unpaired tests. three and seven days of treatment (mean (SEM)); ANP, atrial natriuretic peptide; PRA, plasma renin activity. *p < 0 05 v basal concentrations (day 0). 154 Adesanya, Anjorin, Sada, Parry, Sagnella, MacGregor

Discussion peptide 59-2 pg/ml) had heated her body but The exact cause of peripartum heart failure is not taken an extra salt load. The intense yet to be identified. It occurs throughout the vasodilatation caused by lying on a heated bed world, but is most common in the tropics and in a hot and humid room, and taking very hot the tropical parts of temperate countries where baths twice a day for 40 days may have Br Heart J: first published as 10.1136/hrt.65.3.152 on 1 March 1991. Downloaded from hot and humid climatic conditions prevail.' increased her blood volume enough to induce The high incidence in and around the northern heart failure. Nigerian city ofZaria, especially during the hot Before treatment in the patients with and humid period of the year, has been peripartum heart failure plasma aldosterone attributed in part to the postpartum practice of and plasma renin activity were within the salt loading and body heating in hot and humid normal range but were slightly lower than in rooms.2 Not all of the women who carry out the controls (table 3). Treatment reduced the these practices develop peripartum heart plasma concentration of atrial natriuretic failure, however. It is possible that renal peptide and increased plasma aldosterone and handling ofsalt is different in those who develop plasma renin activity (figure). These changes peripartum heart failure. Urinary sodium in most probably reflect the associated reduction spot samples before treatment in the patients in the extracellular fluid volume. Atrial with peripartum heart failure were significantly natriuretic peptide may be one of the many lower than those in the controls (table 2); this factors that are important in the control of suggests sodium and water retention. This renin release.8 Before treatment atrial resultant salt and water rt ceiation could cause a natriuretic peptide may have been sufficiently high output cardiac failure. But very little is raised to contribute to the observed suppres- known about the associated hormonal respon- sion of renin and aldosterone. ses. In the present study we measured plasma In conclusion, patients with peripartum concentrations of atrial natriuretic peptide, heart failure have raised concentrations of aldosterone, and renin in the women who plasma atrial natriuretic peptide and sup- developed peripartum heart failure and those pressed concentrations of plasma aldosterone who did not have heart failure after the post- and renin. This accords with heart failure partum rituals. Previous studies have shown induced by hypervolaemia. The heart failure that plasma concentrations of atrial natriuretic responded rapidly to treatment and the concen- peptide increased in healthy individuals during trations of circulating hormones were restored increased sodium intake3 and much increased to normal. concentrations were reported in patients with overt heart failure.78 In patients with heart We thank Mr M G Buckley, Mrs M Miller, and Dr A L Sugden failure, the high concentrations of atrial for the plasma hormone measurements. natriuretic peptide before treatment may, therefore, be a response to both the heart 1 Davidson NMcD, Parry EHO. Peripartum cardiac failure. Q JMed 1978;47:431-61. http://heart.bmj.com/ failure and to sodium retention; after correc- 2 Sandersen JE, Adesanya CO, Anjorin FI, Parry EHO. tion of the heart failure atrial natriuretic Postpartum cardiac failure-heart failure due to volume peptide concentrations return overload? Am Heart J 1979;97:613-21. usually towards 3 Sagnella GA, Markandu ND, Shore AC, MacGregor GA. normal.9 In the patients with peripartum heart Effects of changes in dietary sodium intake and saline infusion on immunoreactive atrial natriuretic peptide in failure in the present study atrial natriuretic human plasma. Lancet 1985;ii: 1208-1 1. peptide was considerably reduced after treat- 4 Demakis JG, Rahimtoola SH, Sutton GG, et al. Natural course of peripartum cardiomyopathy. Circulation 1971; ment (figure). It would have been interesting to 44:1053-61.

measure atrial natriuretic peptide during salt 5 Meadow WR. Postpartum heart disease. Am J Cardiol on September 29, 2021 by guest. Protected copyright. and 1960;6:788-92. loading heating, but this was impracticable 6 Talabi AI, Gaba FE, George BO. Puerperal cardiomyopathy because at this stage patients stayed at home. in Lagos. Tropical Cardiology 1985;1 1:73-8. 7 Richards AM. Human plasma atrial natriuretic peptide Plasma concentrations of atrial natriuretic concentration in health and disease. Current Opin Cardiol peptide in patients were extremely high (in 1987;2:660-70. excess of 100 before treatment but 8 Weidmann P, Saxenhofer H, Ferrier C, Shaw SG. Atrial pg/ml) two natriuretic peptide in man. Am J Nephrol 1988;8:1-14. ofthe seven patients had plasma concentrations 9 Anderson JV, Woodruff PWR, Bloom SR. The effect of treatment of congestive heart failure on plasma atrial of atrial natriuretic peptide below 100 pg/ml. natriuretic peptide concentration: a longitudinal study. Br One of these (case 6: plasma atrial natriuretic Heart J 1988;59:207-1 1.