K M Fox

Chest pain in women : clinical, investigative, and prognostic features

Abstract Objective: To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. Design: Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. Setting: Cardiothoracic centre Subjects: Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. Main outcome measures: Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. Results: Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P<0.001). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P=0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P<0.001 and 76% v 95%, P<0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. Conclusions: In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.

Morphology of ambulatory ST segment changes in patients with varying severity of coronary artery disease. Investigation of the frequency of nocturnal ischaemia and coronary spasm.

The frequency and magnitude of objectively determined myocardial ischaemia during normal daily activities of patients with varying severity of coronary artery disease are unknown. Furthermore, the incidence of nocturnal resting myocardial ischaemia and frequency of coronary spasm in patients with normal coronary arteries and chest pain are also not known. One hundred consecutive patients with chest pain referred for coronary angiography were therefore investigated with exercise testing and ambulatory ST segment monitoring. Fifty two of 74 patients with significant coronary artery disease and six of 26 with no significant coronary narrowing had episodes of ST segment change during 48 hours of ambulatory monitoring. Two patients, one with normal coronary arteries and localised spasm and one with three vessel disease, had episodes of ST segment elevation, whereas all other patients had episodes of ST segment depression. The frequency, duration, and magnitude of ST segment changes were greater in patients with more severe types of coronary artery disease. Thus more than six episodes of ST segment change per day occurred in patients with two or three vessel disease or left main stem stenosis and in the only patient with coronary spasm and normal coronary arteries. Nocturnal ischaemia occurred in 15% of patients with coronary artery disease and was almost an invariable indicator of two or three vessel coronary artery disease or left main stem stenosis. Episodes of ST segment change occurred most commonly during the morning hours and least commonly during the night, in parallel with changes in basal hourly heart rates. The heart rate at the onset of ST segment change tended to be lower in patients with coronary artery disease than in those with normal coronary arteries. The duration of exercise to ST segment depression tended to be shorter in patients with more severe disease, but it could not predict patients with nocturnal myocardial ischaemia, left main stem stenosis, or coronary spasm, whereas ambulatory ST segment monitoring was able to identify most of these patients.

The effects of nifedipine on acute experimental myocardial ischemia and infarction in dogs.

We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m (81mKr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 μg/kg, and another five received 1.0 μg/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 μg/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 μg/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man. Circ Res 44: 16-23, 1979

Myocardial ischaemia in patients with frequent angina pectoris.

One hundred patients with angina pectoris underwent 16-point electrocardiographic (ECG) mapping of the left hemithorax during a standardised exercise test. Forty-five patients had maximum ST-segment depression at position V5, while 35 had no ECG signs of ischaemia at this position. In 20 V5 was on the edge of the precordial area, which showed less severe ST-depression than the central positions. An Oxford ECG recorder and highspeed analyser were modified and used in 50 of the patients with daily angina for recording ST-segment changes over 24 hours. Serial 24-hour ambulatory recordings from the edge of the precordial area of ischaemia identified during exercise detected a mean of only 14 +/- SD 3% of the episodes of ST-segment changes recorded from the centre of the same area. Only 16 +/- 2% of the episodes detected by ECG were accompanied by chest pain. More episodes occurred between 4 am and 6 am than at any other time during the night. This study shows the importance of recording ECG evidence of ischaemia from the precordial position showing maximum changes during exercise. ECG evidence of ischaemia occurs more frequently than anginal pain. These objective measurements add important information to the frequency of chest pain reported by patients with ischaemic heart disease.

MECHANISMS OF NOCTURNAL ANGINA PECTORIS: IMPORTANCE OF INCREASED MYOCARDIAL OXYGEN DEMAND IN PATIENTS WITH SEVERE CORONARY ARTERY DISEASE

Changes in heart rate before and throughout episodes of ST-segment depression were recorded during ambulatory electrocardiographic monitoring in five patients with daytime and nocturnal resting angina and six patients with daytime angina only, who all had severe obstructive coronary disease. In 16 of 17 nocturnal episodes and in all the daytime episodes the heart rate increased before the onset of ST-segment depression. There were no significant differences in the sequence and magnitude of changes in daytime, nocturnal, painful, or painless episodes. The maximum heart rate during individual episodes preceded the maximum ST-segment depression by a mean 80.7 s and in the majority of episodes the heart rate returned to baseline before the ST segment. Thus, in severe coronary artery disease the mechanisms producing nocturnal resting ischaemia were apparently similar to those during daytime exertion; increased myocardial oxygen demand not coronary spasm seemed responsible for most of the episodes of nocturnal ischaemia.

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients.

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.

Effect of partial agonist activity in beta blockers in severe angina pectoris: a double blind comparison of pindolol and atenolol.

The use of beta adrenoceptor blockade in the treatment of rest angina is controversial, and the effects on severe angina of partial agonist activity in beta blockers are unknown. Eight patients with effort angina and seven with effort and nocturnal angina and severe coronary artery disease were studied initially when they were not taking any antianginal drugs. Pindolol 5 mg thrice daily (with partial agonist activity) and atenolol 100 mg daily (without partial agonist activity) were given for five days each in a double blind randomised manner. Diaries of angina were kept and treadmill exercise testing and ambulatory ST monitoring performed during the last 48 hours of each period of treatment. Daytime and nocturnal resting heart rates and the frequency of angina were significantly reduced by atenolol compared with pindolol (p less than 0.01). The duration of exercise was significantly increased and the frequency, duration, and magnitude of daytime and nocturnal episodes of ST segment depression on ambulatory monitoring were reduced by atenolol. Reduction in resting heart rate is important in the treatment of both effort and nocturnal angina. Partial agonist activity in beta adrenoceptor antagonists may be deleterious in patients with severe angina pectoris.

Comparison of Doppler derived haemodynamic variables and simultaneous high fidelity pressure measurements in severe pulmonary hypertension.

OBJECTIVE--To assess relations between right ventricular pressure measured with a high fidelity transducer tipped catheter and the characteristics of tricuspid regurgitation recorded with Doppler echocardiography. DESIGN--A prospective non-randomised study of patients with severe pulmonary hypertension referred for consideration of lung transplantation. SETTING--A tertiary referral centre for cardiac and pulmonary disease, with facilities for invasive and non-invasive investigation, and assessment for heart and heart-lung transplantation. PATIENTS--10 patients with severe pulmonary hypertension being considered for lung transplantation. ENDPOINTS--Peak right ventricular, pulmonary artery, and right atrial pressures; peak positive and negative right ventricular dP/dt; peak Doppler right ventricular-right atrial pressure drop; Doppler derived peak positive and negative right ventricular dP/dt; and time intervals of Q to peak right ventricular pressure and to peak positive and negative right ventricular dP/dt. RESULTS--The mean (SD) pulmonary artery systolic pressure was 109 (29) mm Hg. The peak Doppler right ventricular-right atrial pressure drop underestimated peak right ventricular pressure by 38 (21) mm Hg, and by 21 (18) mm Hg when the Doppler value was added to the measured right atrial pressure (P values < 0.05). This discrepancy was greater for higher pulmonary artery pressures. The timing of peak right ventricular pressure differed, with the Doppler value consistently shorter (mean difference 16 ms, P < 0.05). Values of peak positive and negative right ventricular dP/dt and the time intervals Q-peak positive right ventricular dP/dt and pulmonary closure to the end of the pressure pulse differed between the two techniques in individual patients, but not in a consistent or predictable way. CONCLUSIONS--Doppler echocardiography significantly underestimates the peak right ventricular pressure and the time interval to peak right ventricular pressure in pulmonary hypertension, particularly when severe. These differences may be related to orifice geometry. Digitisation of Doppler records of tricuspid regurgitation provides useful semiquantitative estimates of absolute values and timing of peak positive and negative right ventricular dP/dt. Clinically significant differences may exist, however, and must be considered in individual patients.

Lack of effect of warfarin on the restenosis rate or on clinical outcome after balloon coronary angioplasty.

Between September 1985 and April 1987, 110 consecutive patients who had successful coronary angioplasty were included in a randomised prospective controlled evaluation of the effects of warfarin on restenosis. The warfarin (n = 56) and the control (n = 54) groups were not different in terms of age, sex, previous coronary bypass surgery or coronary balloon angioplasty, severity of symptoms, and frequency of multivessel disease or of total coronary occlusions. Warfarin was started on the day of the procedure and the dosage was adjusted to maintain the thromboplastin international normalised ratio greater than or equal to 2.5. One hundred and five (96%) of the patients were given verapamil and other antianginal drugs were prescribed as needed. Low molecular weight dextran and heparin were given during the procedure and heparin was continued for 24 hours in all patients. One hundred and eight (98%) of patients were followed up clinically after a median of five months (range 1-20). Eighty five (77%) had follow up angiography at five months. In the warfarin group symptoms improved in 46 (85%) patients by at least 1 angina class and 31 (57%) were symptom free; the exercise test remained positive in 20 (36%) patients and the angiographic restenosis rate was 25% per lesion and 29% per patient. There were no major bleeding complications. In the control group 46 (85%) patients were improved by at least 1 angina class and 31 (57%) were symptom free; the exercise test was positive in 11 (21%) patients and the angiographic restenosis rate was 33% per lesion and 37% per patient. Although the incidence of angiographic restenosis tended to be lower with warfarin, none of these differences was significant. These data suggest that the combination of verapamil and warfarin, in the absence of aspirin, is not significantly better than verapamil alone in preventing symptom recurrence or angiographic restenosis after coronary angioplasty.

Medical treatment of patients with severe exertional and rest angina: double blind comparison of beta blocker, calcium antagonist, and nitrate.

The role of medical treatment of patients who had resting nocturnal angina as well as exertional angina was investigate. The effects of atenolol 100 mg a day, nifedipine 20 mg three times a day, and isosorbide mononitrate 40 mg twice a day were investigated in a double blind, triple dummy randomised study. Nine patients with coronary artery disease, early positive exercise tests, and transient daytime and nocturnal ambulatory ST segment changes were initially assessed off all antianginal medication. They were then treated with each drug for three five day periods. Angina diaries were reviewed and maximal treadmill exercise tests and 48 hour ambulatory ST segment monitoring were performed at the end of each treatment period. Resting and exercise heart rate and blood pressure were significantly lower on atenolol than on either isosorbide mononitrate or nifedipine. The duration of exercise to 1 mm ST segment depression was significantly greater on atenolol than on isosorbide mononitrate. Only one patient had an improvement in exercise tolerance on nifedipine that was greater than the improvement on atenolol; this patient had single vessel disease. The total number and duration of episodes of ST segment change during ambulatory monitoring were significantly lower with atenolol than on either isosorbide mononitrate or nifedipine. Nocturnal ST segment changes were abolished in six patients on atenolol, in six patients on nifedipine, and in five patients on isosorbide mononitrate. When nocturnal ST segment changes occurred, their frequency was reduced with all three drugs. Pain was abolished in four patients on atenolol and pain relief was significantly better on atenolol than on isosorbide mononitrate. There was no significant difference in pain relief between isosorbide mononitrate and nifedipine. Thus beta receptor blockade with atenolol was the most effective means of reducing myocardial ischaemia both during exercise and at rest at night without causing deterioration in any patient. Nocturnal myocardial ischaemia in patients with severe coronary artery disease can be effectively treated with beta receptor antagonists and vasodilators.