© 2001 European Society of Cardiology
Cardiac peptides and plasma renin activity in acute dilated cardiomyopathy
Blood Pressure Unit, St George's Hospital Medical School Cranmer Terrace, London SW17 0RE, UK
* Corresponding author. Tel.: +44-181-725-5774; fax: +44-181-725-2959. E-mail address: missouris{at}AOL.com (C.G. Missouris).
Received November 9, 1999; Revised March 8, 2000; Accepted June 13, 2000
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1. Case history |
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 Top 1. Case history References |
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A 33-year-old Caucasian man was admitted to the Coronary Care Unit of our Hospital with a 2-day history of mild shortness of breath on exertion and a 4-h history of central retrosternal chest discomfort that radiated to the left arm. He was a non-smoker and drank 10 units of alcohol weekly. His father was diagnosed, age 53, as suffering from dilated cardiomyopathy. There was no family history of premature coronary artery disease.
On examination, he was apyrexial. Supine heart rate was 114 beats/min and blood pressure was 118/84 mmHg. There were no clinical signs of heart failure. The resting 12 lead ECG showed sinus tachycardia, slow R wave progression, biphasic T waves, and 2 mm ST elevation in the precordial leads V1–V3. The anteroposterior chest radiograph revealed mild increase in cardiothoracic ratio, with prominent pulmonary vessels. There were no radiological signs of pulmonary oedema.
The serum creatinine was in the normal range at 87 µmol/l. There was mild elevation in the cardiac enzymes: creatinine phosphokinase 522 U/l (normal range 30–250 U/l), aspartate transaminase 82 U/l (normal range 10–35 U/l), and lactate dehydrogenase 294 U/l (normal range 100–200 U/l). The total fasting cholesterol was 5.1 mmol/l (HDL 0.7 mmol/l, LDL 3.7 mmol/l). In view of the clinical history and ECG findings he was treated with oral aspirin and intravenous thrombolytic therapy.
The patient continued to experience chest discomfort and therefore left heart catheterisation was undertaken 24 h after admission (day 1). This demonstrated normal epicardial coronary arteries and a grossly dilated left ventricle with severe impairment in systolic function. The latter was also confirmed using transthoracic echocardiography. The left ventricular end diastolic and systolic diameters were 7.0 and 6.2 cm, respectively (fractional shortening <15%). Right ventricular endomyocardial biopsy was not performed due to the risks involved in performing the above procedure.
As a result of the above findings he was treated with an angiotensin converting enzyme (ACE) inhibitor (enalapril 2.5 mg twice a day), frusemide 40 mg daily and warfarin. Blood samples were taken for measurement of plasma renin activity (PRA), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) before this treatment was commenced. Repeat measurements of these hormones were made on days 3, 8 and 15. During this time weight did not increase. The patient was discharged home on enalapril 5 mg b.d. and frusemide 40 mg o.d. The ACE inhibitor was not increased further due to the tendency for the blood pressure to fall on the above treatment (supine 98/78 mmHg and standing 96/66 mmHg). When he was seen in our clinic on day 15, he was symptom free and his weight was 99.5 kg.
On admission, before diuretic and ACE inhibitor were given, plasma renin activity was in the normal range at 0.49 ng/ml/h (normal value: 0.5–2.5 ng/ml/h). However, plasma levels of both BNP and ANP were markedly elevated at 364 pg/ml and 223 pg/ml, respectively (normal values: BNP, 3.9±0.3 pg/ml; and ANP, 8.6±0.8 pg/ml). Following treatment with a diuretic and an ACE inhibitor plasma PRA increased to 17.3 ng/ml/h (day 3). Both BNP and ANP fell initially to 300 and 86 pg/ml, respectively. However, after discharge plasma BNP and ANP rose to 564 and 131 pg/ml, respectively (day 15) (Fig. 1).
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Three months later the patient was admitted at another hospital with symptoms and signs of severe biventricular heart failure and non-sustained ventricular tachycardia, requiring further increase in diuretic therapy and the addition of amiodarone 200 mg daily. The patient is currently on the evaluation list for orthotopic cardiac transplantation.
The cardiac hormone ANP has an important role in the regulation of blood volume and is predominantly secreted by the atria with recruitment of ventricular synthesis in heart failure [1]. In contrast BNP has been shown to be synthesised in the human heart in the atria and in the ventricles in normal physiology, and increases in proportion to the severity of heart failure [2]. Our patient once again clearly demonstrates that in acute left ventricular dysfunction, which in this patient was due to dilated cardiomyopathy, with no overt clinical evidence of sodium and water retention, both BNP and ANP are markedly increased with no increase in plasma renin activity. This suggests that the rise in both cardiac peptides is due to changes in left ventricular function, rather than retention of sodium and water. This is supported by the fact that there were only transient falls in BNP and ANP with diuretic and ACE inhibitor, and no loss of weight. When LV function deteriorated further following discharge, the cardiac peptides rose once more.
The finding of a normal level of plasma renin activity is consistent with previous observations that the renin angiotensin system is not activated by left ventricular dysfunction or severe heart failure. It only becomes activated when diuretics are given [3,4]. Animal data suggest that the absence of an increase in plasma renin activity in congestive heart failure is probably due to an increase in sodium reabsorption by the macula densa. Indeed, Marumo et al. [5] have recently reported that the NaK/2Cl cotransport, the molecular link between urinary sodium and renin secretion, is increased in the renal tubules in experimental congestive heart failure. Thus, the resultant hypertonic medullary interstitum may account for the failure of activation of the renin–angiotensin system. The rise in plasma renin activity seen in our patient with therapy is in part due to the diuretic, but also due to the addition of the ACE inhibitor, which increases renin release and angiotensin I levels due to reduction in the negative feedback of the reduced angiotensin II levels. This is reflected by an increase in plasma renin activity which measures the rate of generation of angiotensin I, which is not blocked by the ACE inhibitor. Clearly further studies are required to establish the importance of neurohumoral factors that influence endothelial function, such as endothelin, in the pathophysiology of sodium retention in patients with heart failure.
In patients with heart failure there is an increase in cardiac peptides. However, it is difficult to decide how far this increase is due to left ventricular dysfunction or to the associated retention of sodium and water. Our patient appears to distinguish between these as, at the time we saw him, there was only left ventricular dysfunction with no overt retention of sodium and water, and clearly demonstrates that this in itself can cause a rise in cardiac peptides, with no increase in renin release until treatment is started.
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References |
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Top1. Case historyReferences |
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- Burnett J.C., Kao P.C., Hu D.C., et al. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science (1986) 231:1145–1147.
[Abstract/Free Full Text] - Mukoyama M., Nakao K., Hosoda K., et al. Brain natriuretic peptide as a novel cardiac hormone in the humans. J Clin Invest (1991) 87:1402–1412.[Web of Science][Medline]
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[Abstract/Free Full Text] - Marumo R., Kaizuma S., Nokae S., et al. Differential upregulation of the rat Na–K–Cl cotransporter, rBSC1, mRNA in the thick ascending limb of Henle in different pathological conditions. Kidney Int (1988) 54:877–888.[CrossRef]
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