A comparison of nifedipine once daily (Adalat LA), isosorbide mononitrate once daily, and isosorbide dinitrate twice daily in patients with chronic stable angina.

The efficacy of nifedipine gastrointestinal therapeutic system (GITS), 60-90 mg o.d., isosorbide dinitrate, 40-60 mg b.d., and isosorbide mononitrate slow-release, 50-100 mg o.d. was assessed in a six week double-blind, parallel-group study in patients with stable angina on chronic beta-blocker treatment. Of 339 patients who entered the study, 229 were eligible for the valid case analysis of efficacy and 335 for the safety analysis. Nifedipine GITS was significantly better than isosorbide dinitrate (P < or = 0.025) in prolonging time to 1 mm ST-segment depression, time to maximum ST-segment depression, time to occurrence of angina and total exercise duration, in addition to reducing the number of angina attacks and glyceryl trinitrate consumption after six weeks therapy. Nifedipine GITS was also significantly better than isosorbide mononitrate (P < or = 0.025) in prolonging time to occurrence of angina and time to 1 mm ST-segment depression after six weeks therapy. The incidence of headache was considerably higher in both the isosorbide dinitrate and isosorbide mononitrate groups (40% and 41%, respectively) than in the nifedipine GITS group (9.5%, P < or = 0.001), and was the main reason for withdrawal from the study (isosorbide dinitrate 18/99, isosorbide mononitrate 17/99, nifedipine GITS 2/95). Peripheral oedema was more common in patients treated with nifedipine GITS (12.5%) compared to nitrates (2% in both groups, P < or = 0.01), but resulted in withdrawal of only one patient (treated with nifedipine GITS). This study suggests that the efficacy and tolerability of nifedipine GITS is superior to long acting nitrates as second-line therapy to beta-blockade in the treatment of chronic stable angina.

Noonan's cardiomyopathy: a non-hypertrophic variant.

OBJECTIVE: To describe the association of the Noonan's phenotype and a primary, familial non-hypertrophic cardiomyopathy with restrictive pathophysiology. DESIGN: Observational study. SETTING: Tertiary cardiac referral centre. PATIENTS: Affected family members. METHODS: Two generations of a single family were examined and a description of the clinical characteristics and electrocardiographic, echocardiographic, and haemodynamic data of those affected is given. RESULTS: Three family members have classic Noonan's phenotype and all have a non-dilated, non-hypertrophic cardiomyopathy. Inheritance is autosomal dominant but with variable penetrance. The electrocardiograms show increased left ventricular voltages in two patients. On echocardiography left ventricular wall and internal end diastolic dimensions are normal, and there is considerable bilateral atrial enlargement. Systolic function is moderately impaired in one patient and mildly impaired in another. Doppler echocardiography showed restrictive pathophysiology as an early end of left ventricular filling and considerable reversal of flow in the superior vena cava during atrial systole. CONCLUSION: Hypertrophic cardiomyopathy is well described in Noonan's syndrome. This is the first report of a non-hypertrophic cardiomyopathy with echocardiographic and haemodynamic features of restrictive pathophysiology.

Atrial permanent pacing for sinus node dysfunction with absent right superior vena cava.

In patients with sinus node dysfunction and normal atrioventricular conduction, single chamber atrial pacing (AAI or AAIR mode) represents the most physiological treatment. Sinus node dysfunction is recognised in association with an absent right superior vena cava, and we present a case in which complete resolution of symptoms was achieved with endocardial atrial permanent pacing.

Doppler echocardiography of double orifice of the left atrioventricular valve in atrioventricular septal defect.

A left atrioventricular valve having a double orifice is a rare congenital abnormality, and is most commonly described in association with atrioventricular septal defect. We report the Doppler echocardiographic findings of this abnormality and present a case where limited surgical repair has resulted in a favourable outcome.

Normal and stenotic human aortic valve opening: in vitro assessment of orifice area changes with flow.

The ability to measure aortic valve area clinically has emphasized the need to understand the changes in aortic valve orifice area during flow. To compare the performance of normal and stenotic human aortic valves we used a pulsatile flow model that simulated in vivo flow conditions. Five normal autopsy specimens and 15 stenotic valves removed at operation were mounted into the model. Valve function was assessed by analysis of video recordings of valve leaflet motion during flow. Over the flow rates tested normal valves demonstrated a linear increase in orifice area. There was no resistance to leaflet opening and valve closure was rapid. The majority of stenotic valves demonstrated an increase in orifice area at low flow rates. No valve showed any increase in maximal area beyond flow rates of 3 l min-1. Increased leaflet resistance of these abnormal valves resulted in notably slower opening and closing rates. In patients with a high cardiac output and severe stenosis, overestimation of the anatomic orifice area derived by the Gorlin equation can result. This is not related to variability in maximal orifice area.

In vitro measurement of stenotic human aortic valve orifice area in a pulsatile flow model. Validation of the continuity equation.

Aortic valve orifice area estimation in patients with aortic stenosis may be obtained non-invasively using several Doppler echocardiographic methods. Their validity has been established by correlation with catheterization data using the Gorlin formula, with its inherent limitations, and small discrepancies between the methods are present. To evaluate these differences further, 15 patients with severe aortic stenosis (mean transvalvular gradient 70, range 40-130 mmHg) had aortic valve area estimations by Doppler echocardiography using two variations of the continuity equation. The intact valves removed at valve replacement surgery were then mounted in a pulsatile model and the anatomical area was measured (mean 0.67 +/- 0.17 cm-2) from video recordings during flow at 5.4 l min-1. Aortic valve area calculated using the integrals of the velocity-time curves measured at the left ventricular outflow tract and aortic jet (mean 0.65 +/- 0.17 cm2) correlated best with the anatomical area (r = 0.87, P less than 0.001). The area derived by using the ratio of maximum velocities from the left ventricular outflow tract and aortic jet (mean 0.69 +/- 0.18 cm2) also correlated well with the anatomical area (r = 0.79, P less than 0.001). The index between the left ventricular outflow tract and aortic jet maximum velocities was less than or equal to 0.25 in all. In patients with severe aortic stenosis the aortic valve area can be reliably estimated using Doppler echocardiography.

Balloon dilatation of the aortic valve in a pulsatile flow model: assessment of the mechanisms and the magnitude and duration of changes in valve area and gradient.

Eighteen stenotic aortic valves (17 removed at operation) mounted in a pulsatile flow duplicator were dilated with a balloon catheter. Sequential measurements showed that the valve area initially increased from a mean (SD) of 0.52 (0.16) to 0.78 (0.17) cm2. It was 0.73 (0.16) cm2 five minutes after dilatation and this was little changed at four weeks (0.70 (0.15) cm2). Initially the mean transvalvar gradient fell significantly from 54 (27) to 32 (8) mm Hg but increased to 35 (10) mm Hg at five minutes and to 40 (11) mm Hg at four weeks. In six valves stretching of the orifice was the only mechanism responsible for the changes while in the remainder there was tearing through commissures with a greater initial increase in area (0.31 v 0.18 cm2) and a smaller decrease in area at five minutes (0.03 v 0.08 cm2). Fractures of calcific deposits in non-commissural positions were seen in one valve only. This laboratory study of isolated aortic valves showed a significant but small increase in valve area after balloon dilatation, which was greater when commissural tearing had occurred. Recoil of the stretched orifice was complete at five minutes and there was little further change over the next four weeks.

Exercise myocardial perfusion scintigraphy with technetium-99m methoxy isobutylisonitrile: a comparative study with thallium-201.

The evaluation of technetium-99m methoxy isobutylisonitrile for the diagnosis of coronary artery disease requires comparative validation against thallium-201, the established perfusion imaging agent. We have compared myocardial and lung uptake of both radiotracers following maximal exercise in 52 patients: 40 with angiographically proven coronary disease. Qualitative and quantitative image analysis showed the diagnostic sensitivity of technetium-99m methoxy isobutylisonitrile to compare favourably with that of thallium-201 as reflected by the mean number of ischaemic segments identified: 5.6 +/- 2.5 vs 4.8 +/- 2.1 by qualitative analysis, and 5.7 +/- 3.2 vs 5.0 +/- 2.6 segments by quantitative analysis. More reversibly ischaemic segments per patient were identified with technetium-99m methoxy isobutylisonitrile than with thallium-201: 3.6 +/- 2.3 vs 1.8 +/- 1.9. There was a higher exercise myocardial to background count ratio with technetium-99m methoxy isobutylisonitrile: 3.16:1 vs 2.58:1, and the mean exercise lung uptake normalised to left ventricular uptake ('lung index'), was lower for technetium-99m methoxy isobutylisonitrile than for thallium-201 (36 +/- 8% vs 40 +/- 10%). Five of the six patients with abnormal elevation of the thallium-201 exercise lung index also had elevation of the technetium-99m methoxy isobutylisonitrile exercise lung index, and all had extensive coronary artery disease. These results indicate that technetium-99m methoxy isobutylisonitrile is at least as effective as thallium-201 for detecting exercise induced myocardial ischaemia. However, technetium-99m methoxy isobutylisonitrile provides a better image quality and may be a more sensitive marker of defect reversibility. For both radiotracers lung uptake is increased with extensive coronary artery disease and measurement of this variable provides prognostic information.

Laser thermal angioplasty probe ("hot tip") temperature: effects of flow.

The temperature developed by the laser thermal ("hot tip") probe during arterial recanalisation is primarily dependent on the rate of energy delivery and the rate of dissipation to the surrounding medium. While higher probe tip temperatures enhance the efficacy of atheroma ablation, so too is the incidence of adverse effects increased. We studied the temperature developed in the probe tip in an artificial circulation using both saline and blood. In saline the peak probe temperatures were limited to 100 degrees C (boiling point), falling with each increment in flow. Small discrepancies in probes at different times and may be due to malalignment of the optical fibre-metal cap coupling, temperature measurement inaccuracy, tip insulation, or generator output instability. In blood, charring and clot formation insulated the tip raising the temperature (up to 700 degrees C within 5 seconds at 10 W) but also retarded dissipation of heat to the surroundings. The degree of clot and char formation was critical in determining subsequent thermal responses in any particular probe. The unknown rate and quantity of char buildup and changing blood flow during in vivo angioplasty are likely to be important obstacles to developing a reliable thermal feedback control system.

His bundle ablation with the laser thermal probe ("hot tip"): a feasibility study.

Successful percutaneous ablation of the bundle of His requires accurate localization together with delivery of the minimum effective energy to avoid unwanted effects. The energy output from laser sources can be controlled very precisely but is not easily directed to the bundle of His using conventional fiber optics. The laser thermal probe ("hot tip") consists of an optical fiber and a terminal metal cap that is rapidly heated during energy delivery. When applied to cadaver hearts at energies of 100-150 joules (10 watts for 10-15 seconds) the 2.0-mm diameter peripheral artery probe was able to damage the bundle of His without extensive surrounding damage. The right ventricular free wall and interventricular septum were perforated during some applications at these energies leaving a tract with a diameter of less than 2.0 mm. The atrioventricular (AV) membranous septum, Foramen Ovale, right atrial appendage, and septal leaflet of the tricuspid valve were more resistant at these energy levels and perforations were always less than 1.0 mm in diameter. The probe was modified for use during electrophysiological studies and good quality unipolar electrograms were recorded from the metal cap confirming that the probe could be accurately positioned adjacent to the bundle of His. The laser thermal probe deserves further study as a "self directing" ablation tool.

Coronary angioplasty and left ventricular function in single vessel coronary artery disease.

Left ventricular function was investigated in 86 patients with single vessel coronary artery disease before and three to six months after successful angioplasty. Before angioplasty thallium-201 perfusion scintigraphy and technetium-99m gated equilibrium ventriculography in most patients showed that stress testing (exercise and ice water stimulation and isometric handgrip respectively) induced myocardial perfusion defects that were associated with a mean (SD) drop in left ventricular ejection fraction from 64 (6)% to 56 (7)%. After angioplasty there was residual coronary stenosis of less than or equal to 20% of the diameter of the vessel in 78 patients (group 1) and of between 20 and 50% in eight patients (group 2). After the procedure the perfusion defects seen during stress resolved in 86% of group 1 and in 87% of group 2. Despite the apparent improvement in myocardial perfusion left ventricular dysfunction persisted in group 2--that is during stress the left ventricular ejection fraction fell from 65% (6) to 56% (5). In group 1, on the other hand, the improvement in myocardial perfusion was associated with significant improvement in left ventricular function with a normal increase in ejection fraction from 63 (5) at rest to 67 (6) during stress. Radionuclide studies, one to six weeks after angioplasty in 30 group 1 patients showed continuing left ventricular decompensation during stress in nine (30%) of them despite correction of perfusion defects. But reinvestigation three to six months after the procedure showed recovery of left ventricular function with an increase in ejection fraction from 66 (5) at rest to 69 (7) during stress. These data indicate that coronary angioplasty procedures that give a residual stenosis of

The evaluation of ventricular function using gated myocardial imaging with Tc-99m MIBI.

Left ventricular function is an important prognostic indicator in patients with coronary artery disease. We have assessed a method of providing this information as an adjunct to myocardial perfusion imaging using Tc-99m MIBI (2-methoxy-2-methyl-isopropyl-1-isonitrile). Two separate studies, at rest and during exercise, were performed following an injection of 400-600 M Bq of Tc-99m MIBI in 62 patients. Cardiac gating permitted excellent myocardial edge definition during the cardiac cycle. Radionuclide fractional shortening (RFS) was calculated from the anteroposterior (AP) and the septum to lateral wall (SL) axes in diastole and systole. Results were compared with echocardiographic fractional shortening (EFS) and the ejection fraction (EF) obtained from the gated equilibrium blood pool using Tc-99m-labelled red blood cells. The RFS in the AP axis correlated closely with echocardiographic FS (r = 0.89, P less than 0.001). The RFS in both axes was averaged to provide a global RFS. Global RFS correlated closely with LV radionuclide EF (r = 0.83, P less than 0.001). Inter- and intra-observer reproducibility studies have shown a variability for the procedure of less than 10%. In conclusion, gated perfusion imaging with Tc-99m MIBI, provides useful functional information as an adjunct to perfusion imaging.

A pharmacokinetic study of cilazapril in patients with congestive heart failure.

1. The pharmacokinetics of cilazapril and the inhibition of angiotensin converting enzyme (ACE) were investigated in 10 patients with congestive heart failure, NYHA class II-III, receiving diuretics with or without digoxin. 2. Patients received 0.5 mg and 1 mg cilazapril on the first 2 days, followed by 0.5 mg or 1 mg daily for the next 8 weeks, in a single-blind study. Plasma cilazaprilat concentrations and plasma ACE activities were measured by radioenzymatic methods up to 24 h after the first and last doses. 3. After the initial 0.5 mg dose of cilazapril, a mean maximum plasma concentration of cilazaprilat of 6.8 ng ml-1 was observed at 2.3 h. Concentrations declined up to 8 h with a mean half-life of 5.8 h, followed by slower decrease to 24 h. Total clearance, based on data to 24 h, was estimated at 8.5 l h-1, with three-fold inter-individual variation. Mean maximum plasma ACE inhibition was 87%, decreasing to 65% at 24 h. 4. In the multiple dose phase of the study, four patients received cilazapril 0.5 mg daily, and six patients 1 mg daily. Cilazapril accumulation for the 0.5 mg group averaged 77%, but steady state concentrations for the 1 mg group were less than double those of the 0.5 mg group. ACE inhibition profiles at steady state were similar for both groups, and they differed from first dose data only in a somewhat lower inhibition at 24 h. 5. Historical comparison of the first-dose data with those for healthy young volunteers at identical dosage revealed only minor differences in kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermal effects of stationary "hot tip" laser coronary probes: an in vitro assessment.

Percutaneous laser thermal probe angioplasty requires sufficient laser probe flexibility to access the coronary tree. This may entail a loss of axial strength and the resultant slow advancement may lead to unwanted heating of the normal coronary artery proximal to the lesion. To assess the lateral thermal effects of stationary coronary laser probes, laser thermal energy (50-150 J) was delivered to 25 coronary artery segments (diameter 1.9-4.0 mm) in a perfused cadaver heart preparation using a 1.7 mm tip probe. Adherence to the vessel wall occurred in 19 segments, endothelial charring in 8 segments, and perforation in 3 segments. Endothelial charring was seen in 8 of 13 nonperfused segments but in 0 of 12 segments perfused at 60 ml/minute (P less than 0.01). In all three perforations the vessel to probe diameter ratio was less than 1.6:1, perfusion was absent, and traction to dislodge the adherent probe was necessary. Lateral wall damage is a complication of stationary laser probes: smaller-tipped probes which are advanced rapidly at the time of energy delivery may enhance the safety margins of coronary laser thermal probe angioplasty.

Experience with flecainide for the treatment of cardiac arrhythmias in children.

We treated 22 children, aged 3 days to 16 years 6 months (median 11 years 1 month), with flecainide for a variety of arrhythmias where a Class I agent was indicated. In 16, conventional antiarrhythmic treatment had failed. Structural heart disease was present in nine. The arrhythmia was paroxysmal re-entry atrioventricular tachycardia in nine; paroxysmal atrial tachycardia, flutter or fibrillation in five; paroxysmal ventricular tachycardia in five and frequent ventricular extrasystoles (with couplets) in three. Sinus rhythm was achieved in all four children who received flecainide during tachycardia (three received intravenous flecainide, one oral). During follow-up of 3-24 months (median 12 months), arrhythmia control was obtained in 13 children (59%). Combination therapy was used in seven of these; with digoxin in four and a beta blocker in three. Flecainide doses used in this study ranged from 1-11 mg kg-1 day-1 (median 4 mg kg-1 day-1), 25-297 mg m-2 day-1 (median 113 mg m-2 day-1). The median, pre-dose flecainide concentration in those responding to therapy was 225 micrograms l-1 and in those failing to respond was 417 micrograms l-1. An arrhythmogenic effect occurred in one child.

Fetal complete heart block.

In a series of over 6000 patients referred for fetal echocardiography during an eight year period, 37 fetuses were found to have complete heart block. There were 16 cases of isolated heart block and 21 cases associated with structural heart disease. All mothers of fetuses with isolated complete heart block had evidence of circulating syndrome Sjögren A antibody (Ro). Only one mother had clinical evidence of connective tissue disease. In the 21 cases associated with structural heart disease there were 17 cases of atrioventricular septal defect, one case of secundum atrial and perimembranous ventricular septal defects, two cases of tetralogy of Fallot, and one case of pulmonary stenosis. All fetuses with atrioventricular septal defects and complete heart block had left atrial isomerism. Additional abnormalities of the great arteries were often found in this group; these were double outlet right ventricle, transposition of the great arteries, pulmonary atresia, coarctation of aorta, and stenosis of the pulmonary or aortic valves. Intrauterine congestive heart failure was a feature of four cases in the group with isolated complete heart block and 11 cases of the group with associated structural heart disease. The outcome in the fetuses with isolated complete heart block was better than in those with heart disease: 12 of the 16 fetuses are alive, two of them have a pacemaker. But only three of the group of 21 fetuses with cardiac malformation are alive, and two of them have a pacemaker.

Obstetric importance, diagnosis, and management of fetal tachycardias.

During 1980-7, 23 pregnancies of 22-38 weeks' duration were investigated for fetal tachycardia. Twelve were cases of supraventricular tachycardia, eight of atrial flutter, and three cases in which the rhythm varied between supraventricular tachycardia and atrial flutter. In 11 cases the fetus had developed non-immune fetal hydrops before referral; 12 cases were non-hydropic at referral but one of this group of fetuses became hydropic during treatment. No relation was found between the rate or type of arrhythmia and the presence or absence of intrauterine heart failure. One non-hydropic infant was delivered electively prematurely. Maternal antiarrhythmic treatment was instituted in the remaining 22 cases. Conversion of the arrhythmia was achieved with digoxin alone in five cases and with a combination of digoxin and verapamil in nine. Control of the arrhythmia was achieved in seven of the 10 non-hydropic fetuses, and all were delivered at term with no deaths. Of the 12 hydropic fetuses, control was achieved in seven. Only three of the hydropic fetuses were delivered close to term. There were two deaths, both in the hydropic group. Of the whole group, five neonates suffered severe complications of prematurity. In this series the main benefit of treatment appeared to be in prolonging gestation of those hydropic fetuses in which conversion was achieved.

Mianserin and trazodone for cardiac patients with depression.

In a placebo controlled double-blind cross-over study, the cardiovascular and antidepressant effects of three weeks' treatment with mianserin (30-80 mg daily) and trazodone (150-400 mg daily) were studied in depressed patients who had co-existant cardiac disease. In 14 of the 16 patients, no haemodynamic deterioration occurred with either drug. Two patients withdrew from the study. One with coronary artery disease, whose concomitant medication included a calcium-antagonist and a beta-adrenoceptor blocker and who developed severe postural hypotension after his first dose of trazodone while the other had an increased frequency of transient cerebral ischaemic attacks with both mianserin and trazodone, but not with placebo. Mianserin and trazodone are comparable for both antidepressant efficacy and paucity of cardiovascular effects. Although unwanted effects were generally mild, the incidence of dizziness was greater in those patients receiving trazodone. Caution is advised, however, when prescribing either drug to patients with transient cerebral ischaemic attacks or those with coronary artery disease receiving medication.