Multicentre, prospective, randomized trial of 4 vs. 6 French catheters in 410 patients undergoing coronary angiography.

The aim of this study was to assess the quality of angiograms obtained using 4 Fr catheters compared with 6 Fr catheters, the ease of use of the 4 Fr catheters, and the safety of patient mobilization 1 hr following 4 Fr angiography. Details of catheter performance and procedural details were recorded at the time of the angiogram. The angiographic images were scored on the quality and completeness of vessel opacification throughout systole and diastole. A total of 410 patients were recruited. There was no difference between 4 and 6 Fr for procedural variables. All angiograms were considered to be of diagnostic quality. The angiographic scores for the right coronary artery and left ventricular injections were no different between 4 and 6 Fr. However, the angiographic scores for the left anterior descending and circumflex arteries were lower with 4 than with 6 Fr (both P < 0.05). Patients who had 4 Fr angiography mobilized safely at 1 hr and reported significantly less discomfort and bruising than 6 Fr patients. Good-quality diagnostic coronary angiograms can be achieved using 4 Fr catheters with the advantage of earlier postprocedural mobilization and reduced discomfort and bruising for the patient.

Normal coronary angiograms: financial victory from the brink of clinical defeat?

OBJECTIVE: To examine the hypothesis that, in patients undergoing coronary angiography for suspected ischaemic heart disease, a normal angiographic result is associated with a fall in consumption of health care resources following the angiogram. DESIGN: Retrospective cost-benefit analysis comparing the 12 month periods before and after coronary angiography. SETTING: Tertiary cardiac referral centre. SUBJECTS: 69 consecutive patients investigated in the financial year 1991-92 whose angiograms were normal. MAIN OUTCOME MEASURES: Drug and hospital admission costs in the 12 month periods before and after angiography; urgent and elective consultations with general practitioner in that time. RESULTS: The mean cost of care per patient in the year before investigation was 656.89 pounds. A highly significant fall in all indices of resource consumption was observed in the year following investigation, the mean resulting difference in the cost of care being 35.15 pounds per month. The cost of coronary angiography would, if this fall were maintained, be recouped in a mean time of 18 months. CONCLUSIONS: Patients suspected on clinical grounds to have coronary atherosclerosis who are found at angiography to have normal coronary arteries are heavy consumers of health care resources. Early investigation for these patients is safe and has beneficial resource consequences in the medium term.

Postmyocardial infarction ventricular septal rupture in the thrombolytic era: two-year experience at a regional centre.

We review the 2-year experience in one cardiology unit of postmyocardial infarction ventricular septal rupture. Between July 1990 and July 1992 there were 23 such patients for whom records were available, 20 of whom underwent surgical repair. The overall mortality was 48%, and the operative mortality was 40%. The mortality in patients who suffered septal rupture within 48 hours of acute myocardial infarction was 82%, while in those in whom rupture was delayed for more than 48 hours the mortality was 17% (P < 0.001). Despite a local thrombolytic rate of 75% in acute myocardial infarction, only 5 out of 23 had received thrombolytic therapy. In this centre, postinfarction septal rupture is a common reason for emergency referral. Survival in those presenting more than 48 hours after infarction is good; in those presenting earlier the prognosis remains poor, despite surgery.

Increased cardiac sympathetic nervous activity in patients with unstable coronary heart disease.

We have evaluated overall and cardiac sympathetic activity in 47 patients undergoing coronary angiography, 27 with stable angina of at least 3 months duration, and 20 with unstable ischaemic symptoms within this period. Cardiac and overall sympathetic activity were assessed using radiotracer noradrenaline kinetic techniques to measure cardiac and total noradrenaline spillover to plasma. Overall sympathetic activity (whole body noradrenaline spillover) was similar in the two groups, whereas cardiac sympathetic activity (cardiac noradrenaline spillover) was strikingly increased in the patients with unstable ischaemic symptoms (102 +/- 23 pmol.min-1 vs 34 +/- 4 pmol.min-1, P < 0.001), as was the cardiac to whole body noradrenaline spillover ratio (0.043 +/- 0.008 vs 0.021 +/- 0.005, P < 0.01). Coronary sinus bloodflow (50 +/- 4 ml.min-1 vs 38 +/- 4 ml.min-1, P < 0.05) and coronary sinus noradrenaline concentration (2.60 +/- 0.38 nmol.l-1 vs 1.41 +/- 0.17 nmol.l-1, P < 0.01) were also increased in the patients with unstable ischemic syndromes. Left ventricular ejection fraction was similar in the two groups (63 +/- 2% vs 62 +/- 2%). Patients with unstable ischaemic symptoms within the previous three months have increased cardiac sympathetic nervous activity compared to patients with stable angina. This may in part explain why patients with unstable ischaemic syndromes are at increased risk of sudden cardiac death.

Noradrenaline kinetics and coronary haemodynamics during acute beta 1-adrenoceptor blockade in man.

1. To investigate the effects of acute beta 1-adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 micrograms min-1 kg-1) in 10 patients undergoing diagnostic cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 7 days. 2. Coronary haemodynamics were measured in these 10 patients plus two others. Compared with saline placebo, metoprolol administration was associated with decreases in heart rate (68 +/- 2 to 59 +/- 3 beats/min, P < 0.001) and coronary sinus blood flow (86 +/- 8 to 68 +/- 6 ml/min, P < 0.001) and an increase in calculated coronary vascular resistance (1.42 +/- 0.19 to 1.75 +/- 0.22 mmHg min ml-1, P < 0.001). Arterial and femoral venous noradrenaline concentrations, whole-body noradrenaline clearance and whole-body noradrenaline spillover to arterial plasma did not change. In contrast, cardiac noradrenaline spillover (33.7 +/- 5.1 to 20.2 +/- 4.3 pmol/min, P < 0.05) and cardiac noradrenaline clearance (31 +/- 3 to 23 +/- 3 ml/min, P < 0.001) were significantly decreased during metoprolol administration. 3. These results may be explained by inhibition of pre-junctional facilitatory beta-adrenoceptors, which we hypothesize may be predominantly of the beta 1-subtype in the heart and of the beta 2-subtype in the periphery.

Coronary venous noradrenaline during coronary angioplasty.

Coronary venous and arterial noradrenaline concentrations were measured during percutaneous transluminal coronary angioplasty in 14 patients. Coronary venous noradrenaline did not increase significantly during balloon inflation but was increased during early reperfusion in patients undergoing left anterior descending angioplasty (n = 8), from 157 +/- 38 pg/ml to 295 +/- 94 pg/ml (P less than 0.05). Coronary blood flow, measured by thermodilution in 7 further patients during left anterior descending angioplasty, was 69 +/- 9 ml/min, decreased to 80 +/- 3% of basal flow during balloon inflation (P less than 0.01) and increased to 135 +/- 5% during early reperfusion (P less than 0.01). It was estimated using these results that cardiac spillover of noradrenaline did not change during occlusion of the left anterior descending artery, but increased almost 3-fold during early reperfusion. During the period of balloon inflations, there was a modest increase in overall sympathetic tone, as assessed by total noradrenaline spillover to plasma (400 +/- 77 ng/min to 473 +/- 87 ng/min, P less than 0.01). These results, suggesting an increase in release of noradrenaline during early reperfusion following brief occlusion of the left anterior descending artery, may be relevant to the genesis of reperfusion arrhythmias.

Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.

Cardiac and whole-body [3H]noradrenaline kinetics during adrenaline infusion in man.

1. To investigate the possible role of adrenaline as a modulator of noradrenaline release from the sympathetic nervous system, the responses of cardiac and whole-body noradrenaline kinetics to intravenous infusions of adrenaline (30 ng min-1 kg-1) and matching saline placebo were determined at rest and during supine bicycle exercise in 16 patients undergoing cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 72 h. 2. At rest and compared with placebo, infusion of adrenaline was associated with a small increase in arterial plasma noradrenaline from 211 +/- 29 pg/ml to 245 +/- 29 pg/ml (P less than 0.05). Increases in whole-body noradrenaline spillover to arterial plasma were larger (from 282 +/- 40 ng min-1 m-2 to 358 +/- 41 ng min-1 m-2, P less than 0.01) and there was a trend towards an increase in whole-body noradrenaline clearance. Cardiac noradrenaline clearance was modestly increased during adrenaline infusion, but cardiac noradrenaline spillover was not altered despite increases in heart rate and coronary sinus plasma flow. Adrenaline infusion was associated with symptomatic myocardial ischaemia in four of 14 patients with coronary heart disease. 3. Supine bicycle exercise was associated with significant increases in peripheral noradrenaline concentrations and in cardiac and whole-body noradrenaline spillover. The increases on exercise were not significantly different for these variables during saline and adrenaline infusions. 4. Infusion of adrenaline to produce 'physiological' increases in plasma adrenaline concentration was associated with an increase in total noradrenaline release, as assessed by whole-body noradrenaline spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of sympathoneural activity in clinical research.

The assessment of autonomic nervous activity is a frequent and challenging goal of clinical research. The diverse current approaches are reviewed. Direct recording from the sympathetic input to muscle has the advantage of excellent time resolution and directness, but gives no information on the sympathetic input to the internal organs. Plasma noradrenaline concentration has limitations of specificity, some of which are overcome by single isotope radiotracer kinetic techniques. Other chemical markers are less satisfactory. End organ responses are generally limited to cardiovascular and cutaneous autonomic assessment, but sophisticated information is obtainable using power spectral analysis of heart rate variability. Assessment of receptor systems, of first and second messengers and radionuclide imaging of adrenergic nerves all give complimentary information. It is likely that a combination of these diverse techniques will advance understanding of the role of the autonomic nervous system in many disease states.

Plasma noradrenaline as an index of sympathetic tone in coronary arterial disease: the confounding influence of clearance of noradrenaline.

Kinetics of [3H]noradrenaline in the plasma were compared with plasma noradrenaline concentration in assessing overall sympathetic activity in six groups totalling 118 subjects. Arterial plasma noradrenaline in 21 control subjects was 204 +/- 14 pg/ml, similar to 20 patients with stable angina not treated with beta-blockers (194 +/- 25 pg/ml) and to 31 patients with stable angina treated with beta-blockers (232 +/- 19 pg/ml). Plasma noradrenaline was increased in 17 patients with unstable angina (366 +/- 50 pg/ml, P less than 0.01), in 14 patients with recent acute myocardial infarction (460 +/- 44 pg/ml, P less than 0.001) and in 15 patients with treated cardiac failure (582 +/- 78 pg/ml, P less than 0.001). Whole body clearance of noradrenaline from plasma was, however, reduced in each of the last three groups compared to controls by 20% (P less than 0.05), by 34% (P less than 0.01) and by 31% (P less than 0.01), respectively. In the 31 patients with stable angina on beta-blockers, clearance of noradrenaline was also reduced by 20% (P less than 0.05). Whole body noradrenaline spillover, a potentially more accurate measure of overall sympathetic activity than concentration of noradrenaline in plasma, was 235 +/- 20 ng min-1 m-2 in controls, was similar in subjects with stable angina (no beta-blockers; 260 +/- 34 ng min-1 m-2, beta-blockers; 200 +/- 17 ng min-1 m-2), but was increased in patients with unstable angina (310 +/- 27 ng min-1 m-2, P less than 0.05), with recent acute myocardial infarction (346 +/- 40 ng min-1 m-2, P less than 0.05) or with heart failure (438 +/- 65 ng min-1 m-2, P less than 0.01). Overall sympathetic activity is unchanged in stable angina, but is progressively increased in patients with unstable angina, recent myocardial infarction or heart failure. Plasma concentration of noradrenaline fails accurately to reflect this as a result of decreased clearance of noradrenaline in these patients. The results show the potential limitations of measurement of noradrenaline in the plasma as an index of overall sympathetic activity and the importance of assessing clearance.

Selective enhancement of the cardiac sympathetic response to exercise by anginal chest pain in humans.

Cardiac and whole body [3H]norepinephrine kinetics were used to evaluate the response of overall and cardiac sympathetic activity to supine bicycle exercise in 31 patients with coronary artery disease (CAD) and in nine normal control subjects (group 1). Of the 31 patients with CAD, 20 developed evidence of myocardial ischemia during exercise (group 2), typical angina occurring in 20 of 20 and ischemic ST segment changes in 13 of 20, whereas 11 patients developed no evidence of ischemia (no chest pain or electrocardiographic changes) (group 3). Exercise resulted in increased total and cardiac NE spillover in all groups of patients. Basal cardiac NE spillover was similar in the three groups (group 1, 5 +/- 1 ng/min; group 2, 8 +/- 1 ng/min; group 3, 7 +/- 2 ng/min; p = NS), but during exercise, cardiac NE spillover was greater in patients who developed angina (group 2, 30 +/- 5 ng/min) than in those who did not (group 1, 17 +/- 2 ng/min; group 3, 17 +/- 2 ng/min; p less than 0.05). The increases in total NE spillover were similar in the three groups. Supine bicycle exercise increases cardiac and overall sympathetic tone in normal control subjects and in patients with CAD. The occurrence of angina selectively enhances the cardiac sympathetic response to exercise. In the absence of angina, patients with CAD and control subjects without CAD have similar sympathetic responses to exercise.

Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia.

Radiotracer kinetics were used to evaluate the activity of the sympathetic nervous system in 10 patients who had had unstable ischaemic symptoms within the previous 12 weeks and 10 with stable angina. Patients with recent unstable angina or angina after recent acute myocardial infarction had higher basal cardiac noradrenaline spillover than patients with stable angina. This represents a selective increase in cardiac sympathetic tone because whole body noradrenaline spillover was not significantly increased in the patients with recent unstable angina. Atrial pacing in 15 patients caused angina in 13 but did not significantly alter cardiac noradrenaline spillover in either patients with stable or unstable angina. The flow of plasma in the coronary sinus increased during pacing but because cardiac noradrenaline extraction decreased cardiac noradrenaline clearance was not significantly altered. Both whole body noradrenaline spillover and clearance were modestly increased by pacing, and arterial noradrenaline concentration was unchanged. Patients with recent symptoms of unstable ischaemia had a sustained and selective increase in cardiac efferent sympathetic tone compared with patients with stable angina, and angina induced by atrial pacing did not cause important cardiac sympathetic activation.

Plasma [3H]noradrenaline kinetics in man: is separation of alumina extracts by high performance liquid chromatography necessary?

1. After an 80 min intravenous infusion of 1-[3H]noradrenaline ([3H]NA) in 19 subjects, the proportion of alumina-extractable 3H due to [3H]NA was 86 +/- 2% in arterial and 78 +/- 2% in venous plasma. [3H]Dihydroxy-phenylethyleneglycol ([3H]DHPG) accounted for 8 +/- 1% in arterial and 13 +/- 1% in venous plasma. [3H]Dihydroxymandelic acid ([3H]DOMA) was not detected. 2. No time-dependent change in the proportion of alumina-extractable 3H due to [3H]NA was seen in either arterial or venous plasma over this period. In venous plasma the proportion of alumina-extractable 3H due to [3H]DHPG increased slightly between 30 and 80 min, from 10 +/- 1% to 13 +/- 1%. 3. The results were unchanged with chronic beta-blockade and with either 1-[2,5,6-3H]NA or 1-[7,8-3H]NA. 4. After [3H]NA infusion in man the radioactivity recovered after alumina extraction is predominantly [3H]NA and thus can be used directly to determine [3H]NA kinetics without the need for metabolite separation.

Incidence of asymptomatic pulmonary embolus following acute myocardial infarction.

In a consecutive series of 150 patients with acute myocardial infarction the incidence of pulmonary embolism in 100 of 116 early survivors was determined by radionuclide lung scanning. No patient had a clinically apparent pulmonary embolus. No scan showed a definite segmental pulmonary embolus. Three scans showed a high probability of subsegmental pulmonary embolus. These results show that pulmonary embolus is now an uncommon and minor problem following myocardial infarction.