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Biomedical subjects

A D Timmis

Publications and source records attributed to A D Timmis.

At least 91 records · Page 5Linked to original sources
PubMed1993

Assessment of Holter ST monitoring for risk stratification in patients with acute myocardial infarction treated by thrombolysis.

OBJECTIVES: To evaluate the role of Holter ST monitoring for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment. There is now a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). Preliminary evidence indicates that Holter ST monitoring may be of prognostic value in patients with acute myocardial infarction, but there are limited data available in patients treated by thrombolysis. METHODS: Prospective observational study of 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis. All underwent 48 hour Holter ST monitoring early after thrombolysis (mean 83, range 48-180 hours) and were followed up for eight (range three to 12) months. RESULTS: Recurrent ischaemic events occurred in 45 patients (fatal reinfarction 17, non-fatal reinfarction 12, unstable angina 16). Also four patients died as a result of progressive heart failure, and a further 15 patients required revascularisation. Analysis of the Holter data showed that 32% of patients had at least one episode of isolated ST depression (> or = 0.1 mV) and 41% either ST depression or elevation (> or = 0.2 mV). Ischaemic episodes were silent in 95% of cases. Event free survival analysis showed a significant association between Holter findings and recurrent ischaemic events (ST depression: p = 0.009; ST depression or elevation: p = 0.002). The association remained significant when the end point was restricted to fatal or non-fatal reinfarction (ST depression: p = 0.005; ST depression or elevation p = 0.001), the period of greatest risk for patients with an abnormal recording occurred early after investigation. An abnormal Holter recording identified patients at risk of early (within 30 days) reinfarction with 79% sensitivity and 60% specificity. Although positive predictive accuracy was low (11%), a normal Holter recording was associated with 98% negative predictive accuracy. CONCLUSIONS: In patients treated by thrombolysis, ST change on Holter monitoring may be useful for identifying patients at increased risk of recurrent ischaemic events, and in particular early reinfarction.

Adult↗
PubMed1993

Reassessment of treadmill stress testing for risk stratification in patients with acute myocardial infarction treated by thrombolysis.

OBJECTIVES: To evaluate the role of a treadmill stress test for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment; there is a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). The treadmill stress continues to be recommended for risk stratification after acute myocardial infarction even though its value has never been formally reassessed in the thrombolytic era. METHODS: Prospective observational study in which 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis underwent an early treadmill stress test and were followed up for 10 (range 6-12) months. RESULTS: Recurrent ischaemic events occurred in 41 patients (unstable angina 15, reinfarction 21, death five) and a further 21 required revascularisation. Both ST depression at a low workload and low exercise tolerance (< 7 metabolic equivalents of the task (METS) were predictive of recurrent events, with respective hazard ratios of 1.93 (95% confidence interval (95% CI) 1.17-3.20; p < 0.01)) and 1.67 (95% CI 1.0-2.78; p < 0.05). These variables identified 50% and 70% of patients who subsequently sustained a recurrent ischaemic event, but the corresponding values for positive predictive accuracy were only 26% and 21%. Thus they are of limited value as a screening measure for identifying patients likely to benefit from invasive investigation and revascularisation. None of the other variables (ST elevation, haemodynamic responses, ventricular extrasystoles, angina) was significantly associated with recurrent ischaemic events. CONCLUSIONS: The treadmill stress test is of limited value for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis.

Adult↗
PubMed1993

Holter ST monitoring early after acute myocardial infarction: mechanisms of ischaemia in patients treated by thrombolysis.

OBJECTIVE: To investigate the mechanisms of Holter ST shift in patients with acute myocardial infarction treated by thrombolysis. DESIGN: Prospective observational study. SETTING: A London district general hospital. SUBJECTS: The study group consisted of 94 patients with acute myocardial infarction treated by thrombolysis. INTERVENTIONS: All underwent early 48 hour Holter ST monitoring and elective coronary arteriography. MAIN OUTCOME MEASURES: Relation of Holter ST shift to multivessel coronary disease, coronary patency, collateralisation, and morphology of the infarct related lesion. RESULTS: There was a trend towards an increased prevalence of Holter ST shift in patients with patency of the infarct related artery and those with multivessel disease. This was only significant in patients with three vessel disease, a significantly higher proportion of whom had > 3 episodes of ST shift (41% v 14%; p = 0.02) or a total duration of ST shift > 1 hour (35% v 13%; p = 0.04) than those with less extensive coronary disease. Holter ST shift occurred in a significantly higher proportion of patients with complex lesion morphology (Ambrose type 2 or 3) compared with those with lesions of Ambrose morphology type 1 or 2 (60% v 33%; p = 0.05). CONCLUSION: Holter ST shift detected early after thrombolysis is an ischaemic phenomenon with a complex pathophysiology. It reflects both remote ischaemia in patients with multivessel disease, and dynamic ischaemic processes related to complex lesion morphology in those with a patent infarct related artery.

Adult↗
PubMed1993

Myocardial ischaemia and angina in the early post-infarction period: a comparison with patients with stable coronary artery disease.

OBJECTIVE: To evaluate Holter and treadmill responses in patients with stable angina or recent myocardial infarction in order to compare the mechanisms of ischaemia and its symptomatic expression in these two groups. PATIENTS: 75 patients with ischaemic ST segment depression on both a treadmill stress test and ambulatory Holter monitoring. Group A comprised 35 patients with stable angina, and group B comprised 40 patients in the early period after infarction. SETTING: The coronary care unit and cardiology department of a district general hospital. DESIGN: A prospective, between group, comparative study. RESULTS: Treadmill test showed demand driven ischaemia in both groups. Although ST depression occurred at comparable rate-pressure products and workloads, it was associated with angina in 80% of group A compared with only 40% of group B (p < 0.005). During Holter monitoring, ST depression was associated with an attenuated increase in rate in group A and almost no increase in rate in group B (18.2% v 3.7%; p < 0.005), suggesting that reductions in myocardial oxygen delivery were contributing to the ischaemic episodes, particularly in group B. Ischaemic episodes were more commonly silent during Holter monitoring, particularly patients in group B, only two of whom experienced angina in association with ST depression. Spectral and non-spectral measures of heart rate variability were significantly reduced in group B compared with group A. Patients with silent exertional ischaemia in group A had significantly less heart rate variability than patients who experienced angina but this difference was not seen in group B. CONCLUSION: In stable angina, myocardial ischaemia is usually painful and demand driven, whereas in the early period after infarction silent, supply driven ischaemia predominates. The failure of myocardial ischaemia to provoke symptoms in some patients with stable angina may be related to autonomic dysfunction affecting the sensory supply to the heart. In the early period after infarction despite clear evidence of autonomic dysfunction, other mechanisms must also be important as there was no tendency for the reduction in heart rate variability to be exaggerated in the subgroup with silent exertional ischaemia.

Angina Pectoris↗
PubMed1992

Clinical impact of introducing thrombolytic and aspirin therapy into the management policy of a coronary care unit.

PURPOSE: To evaluate the impact of introducing thrombolytic and aspirin therapy into the management policy of a coronary care unit, with particular reference to its effects on the hospital course of nonselected patients with acute myocardial infarction. End points chosen were the utilization of thrombolytic and aspirin therapy, hospital mortality, discharge diuretic requirements, and the incidence of ventricular fibrillation and cardiogenic shock. PATIENTS AND METHODS: A total of 336 patients with acute myocardial infarction were studied, comprising consecutive admissions to the coronary care unit over two separate 12-month periods: January to December 1986 (n = 158) and September 1989 to August 1990 (n = 178), before and after thrombolytic and aspirin therapy had been introduced into the management policy of the unit. RESULTS: Thrombolytic and aspirin therapy was given to 87% and 93%, respectively, of all patients in the 1989/1990 cohort. This high treatment rate led to substantial improvements in morbidity and mortality. Thus, comparison of the 1986 and 1989/1990 cohorts showed reductions in hospital mortality (24% to 11%, p less than 0.005), ventricular fibrillation (22% to 13%, p = 0.05), and cardiogenic shock (20% to 6%, p less than 0.001), particularly in patients aged over 60. Reductions in the incidence of lesser degrees of heart failure are reflected in the proportions of patients discharged with diuretic requirements, which declined from 43% in 1986 to 22% in 1989/1990 (p less than 0.001). The duration of hospital stay for patients who survived showed no change between 1986 and 1989/1990, but time spent in the coronary care unit decreased from 3.1 +/- 1.8 to 2.1 +/- 1.4 days (p less than 0.001). CONCLUSION: The great majority of nonselected patients with acute myocardial infarction are candidates for thrombolytic and aspirin therapy, which can be given safely, leading to profound reductions in mortality and the incidence of major complications, particularly in the older age group.

Age Factors↗
PubMed1992

Calcitonin gene-related peptide: a haemodynamic study of a novel vasodilator in patients with severe chronic heart failure.

The haemodynamic and neurohumeral response to a novel vasodilator calcitonin gene-related peptide was assessed in 11 patients with severe chronic heart failure. To assess tolerance, a continuous 48-h infusion (n = 6) was compared with a regimen of two successive 8-h infusions (n = 5). Haemodynamic response profiles were similar for both regimens, though the continuous infusion was poorly tolerated. Reductions in afterload reflected by changes in systemic vascular resistance and systemic blood pressure led to increases in cardiac index of at least 24%. Increments in heart rate accounted for much of the increase in cardiac output, there being no significant change in stroke volume index. The response was maintained over the 48-h study period with no tachyphylaxis. Renin and angiotensin levels increased significantly after 24 h. Calcitonin gene-related peptide exerts a favourable haemodynamic response in patients with severe heart failure. The dose used in this study, however, caused troublesome side-effects, particularly when given by continuous infusion. Further studies are required to establish the therapeutic range of this new peptide.

Aged↗
PubMed1992

Streptokinase induced defibrination assessed by thrombin time: effects on residual coronary stenosis and left ventricular ejection fraction.

OBJECTIVE: To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital. DESIGN: Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction. SETTING: The coronary care unit of a district general hospital. PATIENTS: 44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3-9) days later. MAIN OUTCOME MEASURES: Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35). RESULTS: Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = -0.43, p < 0.005) and left ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or = 31 seconds (p < 0.01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables. CONCLUSIONS: Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.

Aged↗
PubMed1991

The perception of angina in diabetes: relation to somatic pain threshold and autonomic function.

Silent ischemia is common in diabetic patients with coronary heart disease. These patients may also have more subtle alteration in the perception of angina as reflected by prolongation of anginal perceptual threshold--the time from onset of 0.1 mV ST segment depression to the onset of chest pain during treadmill exercise. Silent ischemia may be associated with a generalized hyposensitivity to pain, although the pathophysiologic mechanism is obscure. The purpose of the present study was to determine whether diabetic patients with prolonged anginal perceptual thresholds are also hyposensitive to painful stimuli and to investigate whether this is associated with autonomic neuropathy. Nineteen diabetic and 25 nondiabetic patients with exertional angina were exercised on a treadmill to measure anginal perceptual threshold. Somatic pain threshold was measured by calf sphygmomanometry. The cuff was inflated rapidly until pain occurred, and six repeat inflations were done to test reproducibility. Because there was no significant difference between measurements (coefficient of variation = 0.156) the mean value for each patient provided a measure of somatic pain threshold. The diabetic group had a longer anginal perceptual threshold (138 +/- 64 seconds vs 34 +/- 51 seconds, p less than 0.001), which correlated positively with the somatic pain threshold (r = 0.5, p = 0.03); patients with more prolonged anginal perceptual thresholds tended to have higher somatic pain thresholds. In the diabetic group anginal perceptual (r = -0.3, p = NS) and somatic pain (r = -0.4, p = 0.05) thresholds tended to increase as the ratio of peak to minimal heart rate during the Valsalva maneuver fell below 1.21, but these variables were unrelated in the nondiabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1991

Irregular coronary lesion morphology after thrombolysis predicts early clinical instability.

After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗
PubMed1991

Pulmonary microvascular permeability in patients with severe mitral stenosis.

Patients with rheumatic mitral stenosis often have no pulmonary oedema despite considerably increased pulmonary venous pressure. Pulmonary microvascular permeability was measured non-invasively by a previously validated method of double isotope scintigraphy with indium-113m and technetium-99m. This permits calculation of an index reflecting transferrin efflux and thus, indirectly, the microvascular permeability. Fifteen patients with severe mitral stenosis (defined as valve area less than 1.0 cm2) were compared with a control group of 11 patients with mild coronary artery disease. The permeability index was significantly lower in patients with mitral stenosis than in the control group. Furthermore, the extent of reduction of the permeability index correlated with the severity of mitral stenosis as reflected by the Gorlin valve area. This finding may account for the relative resistance of these patients to pulmonary oedema despite chronic pulmonary venous hypertension.

Adult↗
PubMed1991

Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury.

OBJECTIVE: To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN: Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING: The coronary care unit of a district general hospital. PATIENTS: 39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS: Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS: Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS: Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting.

Aged↗
PubMed1991

Aging, autonomic function, and the perception of angina.

OBJECTIVE: To determine the effects of age and autonomic function on the perception of angina. DESIGN: Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques. SETTING: Cardiology departments of a district general hospital and a post-graduate teaching centre. SUBJECTS: 82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18). MAIN OUTCOME MEASURES: Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release. RESULTS: Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold. CONCLUSIONS: In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function.

Adult↗
PubMed1991

Deterioration in left ventricular performance during early coronary angioplasty after thrombolysis. Evidence for myocardial salvage.

To investigate the effects of controlled coronary artery reocclusion after successful thrombolysis, we studied 15 patients during early elective angioplasty of the patent infarct-related artery. Eight patients underwent left anterior descending artery dilation, and the other 7 had right coronary artery dilation. In 13 cases, ST-segment elevation developed during balloon occlusion. In all 15 cases, intravenous digital subtraction left ventriculography during balloon inflation showed that the ejection fraction decreased at least 5% (mean decrease, from 60% to 47%), despite preexisting Q waves overlying the infarct territory in 5 patients. Balloon inflation resulted in decreased apical segmental shortening in all 8 patients who underwent left anterior descending artery dilation; likewise, balloon inflation produced impairment of inferior-wall contraction in all 7 patients who had right coronary artery dilation. In this setting, a deterioration in left ventricular performance indicates that the restoration of coronary patency with thrombolysis has resulted in myocardial salvage. In patients with Q waves, such deterioration suggests that this electrocardiographic abnormality does not necessarily indicate a completed infarction.

Journal Article↗