E. B. Raftery

Fibrinogen, factor VII clotting activity and coronary artery disease severity

To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease.

Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle.

Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment. Hypertension was present in nine (26%) but only three (9%) had electrocardiographic left ventricular hypertrophy. Echocardiography showed ventricular hypertrophy in 12 (48%) and increased left ventricular mass in 17 (68%) patients. Holter monitoring detected important ventricular arrhythmias in 14 patients. Thallium-201 scanning showed evidence for coronary heart disease in eight patients. Systolic time intervals were normal except when there was coexistent ischaemic heart disease. A comparison between 19 acromegalic patients with no other detectable cause of heart disease and 22 age matched controls showed appreciably abnormal left ventricular diastolic function in the group with acromegaly. The abnormalities shown did not correlate with left ventricular mass or wall thickness. There was no difference in diastolic function between patients with active acromegaly and those with treated acromegaly. Hypertensive acromegalic patients had worse diastolic function than hypertensive controls, suggesting that hypertension may further impair the left ventricular diastolic abnormality in acromegaly. This is the first study to find evidence of subclinical cardiac diastolic dysfunction in acromegaly and it supports the suggestion that there is a specific disease of heart muscle in acromegaly.

VERAPAMIL IN CHRONIC STABLE ANGINA: A Controlled Study with Computerised Multistage Treadmill Exercise

Abstract The efficacy of verapamil (360 mg daily) in the treatment of patients with chronic stable angina pectoris was compared with placebo. 28 patients were studied in a placebo-controlled double-blind crossover trial of 2 weeks each and afterwards on long-term verapamil. Exercise tests were performed at the end of the placebo period, and after 2 weeks and 4 weeks on verapamil. On placebo, angina developed in all 28 patients during treadmill tests; the mean exercise time was 6·6 min (SEM ±0·5 min). The mean exercise time increased to 9·2 (±0·8) min at 2 weeks, and 11·2 (±0·8) min at 4 weeks on verapamil. In 15 and 20 patients out of the 28 angina did not develop during treadmill exercise at 2 and 4 weeks respectively. Trinitrin consumption also decreased. There was a significant improvement in ST-segment changes. Constipation (in 7 patients) and reversible PR-interval prolongation (in 2 patients) were the only side effects. No patient had clinical signs of heart-failure. Thus verapamil (360 mg daily) may be useful in the management of chronic stable angina.

Combined therapy with verapamil and propranolol in chronic stable angina

The comparative efficacy of verapamil (360 mg daily) and propranolol (240 mg daily) was evaluated with computerized treadmill exercise in 22 patients with chronic stable angina in a placebo-controlled double-blind crossover study with 4 weeks on each active phase. Fourteen of these patients still had angina despite active drug therapy and they were further treated with a combination of verapamil (360 mg) and propranolol (120 mg) for 4 weeks. The mean exercise time for these patients taking placebo was 4.8 +/- 0.22 minutes (mean +/- standard error of the mean) and this increased to 6.8 +/- 0.64 minutes with propranolol and 8.0 +/- 0.5 minutes with verapamil. A further increase to 10.1 +/- 0.88 minutes was observed with the combination of both drugs and seven patients became symptom-free. S-T segment criteria improved with both drugs, and combination therapy produced a further reduction in peak S-T depression. Electrocardiographic ambulatory monitoring showed no evidence of conduction defects and mean hourly heart rates were similar to those seen with propranolol alone. Left ventricular function indexes were not significantly different from those obtained with propranolol. Combination therapy with verapamil and propranolol appears to be efficacious in the treatment of selected patients with severe chronic stable angina. The patients need to be carefully monitored for adverse effects.

Ambulatory ST segment monitoring. Problems, pitfalls, solutions, and clinical application.

The introduction of frequency modulated recording systems for ambulatory electrocardiographic monitoring (Oxford Medilog mark 2 and Cardiodyne cassette recorders) prompted comparison with a conventional direct recording type of recorder (Oxford Medilog mark 1). The recordings obtained by the frequency modulated recorders were very much superior to those obtained by the direct recording type of recorder. The direct recording suffered from poor low frequency response, phase shift, and cable motions artefacts. Correction of these problems with careful attention to electrode application enabled stable graphs to be obtained over 24 hours. The clinical applications were explored by comparing the results of exercie tests with a computer assisted system with frequency modulated ambulatory monitoring in 30 patients. A range of ST deviations from pure ST depressions throughout 24 hours, pure ST elevation, and a combination of ST elevation and depression were seen, suggesting a spectrum of changes hitherto unsuspected in these patients. Painless ST changes were approximately twice as common as those associated with pain. These findings indicate a valuable role for ST segment monitoring in ischaemic heart disease, particularly with the availability of high fidelity modulated tracings which do not distort ST segments.

SUPERIORITY OF 24-HOUR MEASUREMENT OF BLOOD PRESSURE OVER CLINIC VALUES IN DETERMINING PROGNOSIS IN HYPERTENSION

Long-term recordings of blood pressure in an individual could logically be expected to have greater prognostic power than values recorded in the clinic in view of the known inaccuracies and variability of the latter. This feature has been shown to be true in a large series investigated by Perloff and colleagues1. Specific components of the 24h profile may have greater prognostic power than others, ‘basal’ blood pressure (generally equated with night-time resting values) has been thought by some2 to have greater predictive value than that recorded during less standardised activity at other times of day. A further hypothesis is that high intrinsic blood pressure variability may play an independent role in determining cardiovascular pathology when measured either as a global index3 or as a specific component such as the slope of the early morning rise in pressure4.

Synergistic value of simultaneous stress dobutamine sestamibi single-photon-emission computerized tomography and echocardiography in the detection of coronary artery disease

The relative value of exercise electrocardiography, simultaneous dobutamine technetium 99m-sestamibi (MIBI) single-photon-emission computerized tomography (SPECT), and echocardiography were evaluated for the diagnosis of coronary artery disease in patients with chest pain. Sixty-one consecutive patients underwent exercise electrocardiography and simultaneous graded dobutamine echocardiography and MIBI imaging. All patients underwent coronary arteriography. The exercise electrocardiogram was found to be a poor predictor of coronary artery disease (p not significant). Individually, MIBI SPECT and echocardiography were significantly predictive of coronary artery disease (p < 0.001). According to logistic regression analysis, the combined imaging modalities significantly increased the prediction of coronary artery disease for any vessel (p < 0.001), for multiple vessels (p < 0.001), and for the left anterior descending (p < 0.001), for right coronary artery (p < 0.001), and for left circumflex arteries (p < 0.01), compared with either MIBI SPECT or echocardiography alone. The results suggest a synergism in the detection of coronary artery disease when MIBI SPECT and echocardiography are combined during dobutamine stress.

Nifedipine tablets for systemic hypertension: A study using continuous ambulatory intraarterial recording

The action of nifedipine tablets was examined in 17 patients with essential hypertension focusing particularly on the profile of blood pressure (BP) reduction over 24 hours resulting from both twice-daily and once-daily therapy (dose range 40 to 120 mg daily). This new formulation of nifedipine has a more prolonged and lower peak plasma level than an equivalent dose of nifedipine capsules. Our patients were fully ambulant and studied by continuous intraarterial recording techniques. BP responses during isometric and dynamic exercise testing were also observed. Within-patient comparisons of consecutive mean hourly systolic and diastolic BP showed a highly significant effect from twice-daily therapy (p less than 0.001) for nearly the entire day. Also, significantly lower BP was maintained during isometric and dynamic exercise. Mean hourly heart rates were not significantly altered. The profile of action of the single morning dose was initially similar, but its efficacy diminished from 6 P.M. to 8 A.M. on the following day. Side effects were not unduly troublesome and did not cause any patient withdrawals. Four patients developed mild ankle edema. Two others had facial flushing. Nifedipine given twice daily in tablet form, therefore, is an effective antihypertensive drug capable of lowering BP consistently over 24 hours in ambulant patients and during formal exercise testing. We suggest that this agent may be useful as initial therapy for systemic hypertension, although the tablets are not as yet widely available.

Effects of chronic congestive heart failure secondary to coronary artery disease on the circadian rhythm of blood pressure and heart rate

In 20 subjects with chronic congestive heart failure due to coronary artery disease, the 24-hour variability of ambulatory intraarterial blood pressure (BP) was studied using an improved Oxford Medilog system, and correlated with left ventricular function at rest. The mean radionuclide ejection fraction was 27% (range 10 to 42), the mean pulmonary arterial wedge pressure was 18 mm Hg (5 to 37) and the mean cardiac index was 2.8 liters/min/m2 (2 to 3.8). The 24-hour systolic BP and heart rate (HR) variability indexes were less than those of 22 normal volunteers (p less than 0.05) and were strongly correlated (p less than 0.05) with ejection fraction at rest and pulmonary arterial wedge pressure. Stepwise regression showed that a combination of the mean nocturnal HR and the standard deviation of the hourly mean systolic BP values accounted for 67% of the variability in ejection fraction between patients. Similarly, 73% of the variation in pulmonary wedge pressure was explained by combining the 24-hour mean HR and the mean nocturnal HR.

Randomized double-blind comparison of verapamil and nifedipine in chronic stable angina

A randomized double-blind crossover trial was performed in 32 patients with chronic stable angina to compare the antianginal actions of verapamil (120 mg 3 times daily) and nifedipine (20 mg 3 times daily). Efficacy was assessed using objective end points obtained by computer-assisted exercise testing and 24 hour ambulatory monitoring for S-T segment shift. Twenty-eight patients completed the trial. The mean exercise time to produce angina improved from 5.7 +/- 0.3 minutes (mean +/- standard error of the mean) in patients on placebo, to 7.9 +/- 0.5 minutes in those on nifedipine and 10.0 +/- 0.7 minutes in those on verapamil. Similar improvement was seen in all other objective variables. Generally verapamil produced mild bradycardia and nifedipine mild tachycardia. Four patients complained of palpitations and angina after ingestion of nifedipine and were identified by ambulatory monitoring to have tachycardia and persistent S-T depression. These opposite effects on heart rate may explain the differences in efficacy between these 2 potent calcium ion antagonists.