Background-Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Methods and Results-Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr 1 )apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all PϽ0.0001). Vasodilatation to acetylcholine (Pϭ0.01) but not apelin (Pϭ0.3) or sodium nitroprusside (Pϭ0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all PϽ0.05). Systemic infusions of (Pyr 1 )apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all PϽ0.01) but increased heart rate only in control subjects (PϽ0.01). Conclusions-Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure. (Circulation.

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

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We report the results and one-year follow-up of 20 elderly patients (age range 70-82 years) with severe rheumatic mitral stenosis treated by mitral balloon valvuloplasty (MBV). All 20 were breathless at rest despite treatment with diuretics and digoxin. At cardiac catheterization, successful dilatation was achieved in 17 patients: mean transvalvular mitral gradient fell by 45%, mean cardiac output rose by 24% and mean valve area increased by 76%. There was no procedure-related mortality. At one month, 15 patients had experienced an improvement in symptoms of at least one New York Heart Association class and, at one year, ten had maintained this improvement. Three patients proceeded to mitral valve replacement because of a suboptimal symptomatic result. Mitral balloon valvuloplasty can be successfully performed with significant symptomatic benefit in frail elderly patients unfit for surgery and may also be offered to other selected elderly patients as an alternative to surgical treatment.

Objective-To assess the effects on haemodynamic function and symptoms of percutaneous balloon dilatation of mitral stenosis in patients unable to undergo surgical treatment because of associated medical/cardiac problems.

(Br Heart3' 1994;72:486-491) Several techniques have been described for performing percutaneous mitral balloon valvotomy. Lock et al' used a single cylindrical balloon which reached the mitral valve, via atrial septal puncture, over a guide wire which had been advanced to the aorta. The double cylindrical balloon technique of Al Zaibag et al 2provided a larger dilatation and better haemodynamic results. Catheters with a single shaft and two ("Bifoil") or three ("Trefoil") cylindrical balloons attached have been produced.3 Retrograde approach of the balloon to the mitral orifice, with and without transseptal puncture, has also been described.45 These were all "over the wire" techniques using non-compliant balloons and were successful in improving the severity of mitral stenosis.-9 In 1989 the commercial availability of the Inoue balloon introduced a significantly different approach for mitral balloon valvotomy.101' The Inoue balloon had compliance characteristics designed to assist positioning and stability at the mitral orifice and to allow a series of dilatations over a range of sizes (figure). It was provided with a dilator and a double coil guide wire. The Inoue balloon was directed towards the mitral orifice by a curved stylet rather than over a guide wire.We have compared our experience of using cylindrical balloons for mitral valvotomy in 70 patients with the use of the Inoue balloon for a further 70 patients. Most of the patients in this series were elderly, reflecting the more advanced age at which severe mitral stenosis now presents in the United Kingdom. Patients and methods PATIENTS

Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.

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