Quality improvement report: Safety and efficacy of nurse initiated thrombolysis in patients with acute myocardial infarction

ProblemDelay in starting thrombolytic treatment in patients arriving at hospital with chest pain who are diagnosed as having acute myocardial infarction.DesignAudit of “door to needle times” for patients presenting with chest pain and an electrocardiogram on admission that confirmed acute myocardial infarction. A one year period in each of three phases of development was studied.

Background and setting

The goal of the national service framework for coronary heart disease is that by April 2002, 75% of eligible patients should receive thrombolysis within 30 minutes of arriving at hospital. A district general hospital introduced a strategy to improve door to needle times. In phase 1 (1989-95), patients with suspected acute myocardial infarction, referred by general practitioners, were assessed in the coronary care unit; all other patients were seen first in the accident and emergency department. In phase 2 (1995-7), all patients with suspected acute myocardial infarction were transferred directly to a fast track area within the coronary care unit, where nurses assess patients and doctors started treatment.

Key measures for improvement

Median door to needle time in phase 1 of 45 minutes (range 5-300 minutes), with 38% of patients treated within 30 minutes. Median door to needle time in phase 2 of 40 minutes (range 5-180 minutes), with 47% treated within 30 minutes

Strategies for change

In phase 3 (1997-2001), all patients with suspected acute myocardial infarction were transferred directly to the fast track area and assessed by a “coronary care thrombolysis nurse.” If electrocardiography confirmed the diagnosis of acute myocardial infarction, the nurse could initiate thrombolytic therapy (subject to guidelines and exclusions determined by the consultant cardiologists).

Effects of change

Median door to needle time in phase 3 of 15 minutes (range 5-70 minutes), with 80% of patients treated within 30 minutes. Systematic clinical review showed no cases in which a nurse initiated inappropriate thrombolysis.

Lessons learnt

Thrombolysis started by nurses is safe and effective in patients with acute myocardial infarction. It may provide a way by which the national service framework''s targets for door to needle times can be achieved.     

Acute Myocardial Infarction in Doncaster. II—Delays in Admission and Survival

The speed of admission of patients with suspected acute myocardial infarction was observed over a period of 12 months during which a “no refusal” coronary care scheme was functioning, with emphasis on minimizing delay. During the same period the duration of survival of cases diagnosed as coronary thrombosis by the coroner''s pathologist was measured. Comparison of the two series shows that 75% to 80% of the coroner''s cases had died before the median time of notification of the general practitioner by those patients referred to hospital.We argue that the provision of mobile coronary care on request from general practitioners is unlikely to have an appreciable effect in preventing deaths from acute myocardial infarction outside hospital.     

Relation between Serum Cholesterol and Triglyceride Concentration and Haemoglobin Values in Non-anaemic Healthy Persons

In a study of 2,458 healthy non-anaemic subjects a positive correlation was found between haemoglobin levels and serum cholesterol and triglyceride levels. This may be due to simple changes in plasma volume, which may increase when the haemoglobin concentration decreases. Such an association between plasma lipid levels and haemoglobin values might be of importance in the aetiology of coronary heart disease, as a high haemoglobin value is known to be a “risk factor” in myocardial infarction.     

Sudden Death in Hospital after Discharge from Coronary Care Unit

In a group of 339 patients with acute myocardial infarction treated in a coronary care unit, 273 left the unit while improving and were expected to leave hospital alive; 23 had a cardiac arrest or died suddenly while still in hospital—17 died immediately or after temporary resuscitation and six were resuscitated to leave hospital alive. Ventricular fibrillation was found in 13 of the 20 patients attended by the cardiac arrest team. The incidents were scattered from the 4th to the 24th day after the onset of infarction. Risk factors in these “late sudden death” patients were compared with the 250 patients who left the unit while improving and did not die or suffer cardiac arrest. The patients susceptible to late sudden death were characterized early in their hospital course by the findings of severe, predominantly anterior infarction, left ventricular failure, persistent sinus tachycardia, and frequent ventricular arrhythmias. It is suggested that such patients be chosen for prolonged observation in a second-stage coronary care unit.     

Establishment of a Novel Murine Model of Ischemic Cardiomyopathy with Multiple Diffuse Coronary Lesions

Objectives

Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit.

Methods and Results

In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the “modified HypoE mouse”, was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β.

Conclusion

Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background.     

Acute Myocardial Infarction in Doncaster. I—Estimating Size of Coronary Care Unit

A “no refusal” coronary care service (for one year) was offered to a selected sample of 10 general practices (total list 74,657). The patients were admitted to a three-bedded unit in Doncaster Royal Infirmary and data were collected to enable estimation of the size of unit necessary to serve the whole population in the area (census estimate 268,560; total G.P. list 315,811). This estimation was based on:1. The frequency of admission to hospital of suspected acute myocardial infarction in one year, estimated at 978 from the total population.2. The average duration of stay in the unit, which was 2·45 days.3. The distribution of observed occupancy was approximately Poissonian.From these the average expected bed occupancy was calculated as 6·56 and reference to probability tables gave the frequency of overload for different numbers of beds provided. The incidence of acute myocardial infarction in the area is estimated at 275 per 100,000 per annum, on calculations based on the practice list size, and at 323 per 100,000 per annum, on calculations based on census figures.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

Myocardial Infarction and Deep-vein Thrombosis

In a study of 52 patients admitted into the coronary intensive care unit the incidence of deep-vein thrombosis was measured with the ¹²⁵I-fibrinogen test. Of these patients 31 were eventually confirmed to be suffering from acute myocardial infarction. This preliminary study showed that in patients with a confirmed infarct who were not treated with anticoagulants the incidence of deep-vein thrombosis was 38% and in those treated it was 5·5%. In patients who were “severely ill” from whatever the cause there was a high incidence of deep-vein thrombosis (68%).     

Hematocrit and Coronary Heart Disease

Hematocrit values of patients with acute myocardial infarction have been reported by some workers to be higher than those found in controls; this has been denied by others. In these reported studies important postural, postprandial, age and stress effects have not been considered. In the present investigation hematocrits of healthy and coronary subjects were determined under the same “standard basal” conditions, in the morning hours, fasting or after a light breakfast, and in sitting position; patients studied had no acute illness or distress. A mean hematocrit of 49.1 ± 2.4% was observed in 66 men with chronic coronary disease and of 46.8 ± 3.2% in 68 healthy controls of the same age and sex, the difference being highly significant. The increased hematocrit and plasma viscosity in coronary patients creates significantly higher whole blood viscosity than that observed in healthy controls. This hemodynamic factor may be responsible for the development of clinical symptoms of coronary heart disease and possibly of the basic vascular disease itself.     

The changing pattern of ischemic heart disease

Male and female death rates from all the major forms of cardiovascular disease were approximately equal until about 1920. Since that time the male:female ratio in fatal ischemic heart disease (IHD) has risen dramatically, but some closely related diseases such as cerebrovascular disease and uncomplicated angina pectoris have maintained sex ratios close to unity. It is difficult to reconcile this divergent trend in the sex ratio of IHD with a simple stenotic-thrombotic view of myocardial infarction (MI) and it is suggested that the modern epidemic of MI in men may be the result of a disorder of muscle metabolism (“vulnerable myocardium”) superimposed on a relatively stable background of stenotic-thrombotic arterial disease. The proposed mechanism would also help to explain the selective action of some modern “coronary risk factors” (such as cigarette smoking and physical inactivity) which increase the risk of MI but have little or no effect on the risk of developing cerebrovascular disease or uncomplicated angina pectoris.     

Isolated Aortocoronary Bypass Operations in Patients Over 70 Years of Age: A Comparison With Results in Patients 50 to 59 Years Old

The early and late morbidity, mortality and beneficial effects of isolated aortocoronary bypass operations in a group of 35 patients 70 years old or older were compared with those factors in patients 50 to 59 years old. The patients in both groups were matched according to the year in which the operation was done and the number of vessels bypassed. Left ventricular function, estimated by the angiographically calculated ejection fraction, was not statistically different in the two groups. Cardiac index, while adequate in both groups, was significantly lower in the older age group. Comparisons were made of “early” events, such as perioperative myocardial infarction, perioperative death and length of post-operative hospital stay; and of “late” events, including myocardial infarction, angina pectoris, congestive heart failure and death, which occurred after patients were discharged from the hospital. The mean length of follow-up of patients was similar in both groups.In comparing early events in the two groups, there was no statistically significant difference in the incidence of perioperative myocardial infarction, perioperative mortality or mean length of postoperative hospital stays. With regard to late events, there was no statistically significant difference in the incidences of myocardial infarction, angina pectoris or mortality.     

Ischaemic Heart Disease: A Secondary Prevention Trial Using Clofibrate

A trial is reported of the effects of giving clofibrate to prevent progression of pre-existing ischaemic heart disease. There were two groups randomly distributed between clofibrate (350 patients) and placebo (367 patients) regimens. The trial lasted about six years and was conducted in 19 hospitals in Scotland. The criteria of acceptance into the trial were precise and were monitored by one observer. The standards of diagnosis of events were defined and all protocols and electrocardiograms were read blind by one observer.Three categories of patients were admissible to the trial: (1) patients with one myocardial infarction (W.H.O. E.C.G. criteria) between 8 and 16 weeks before the start of the trial; (2) patients with angina of a duration of 3 to 24 months, provided their E.C.G. showed signs of myocardial ischaemia at rest or after exercise; and (3) patients with one recent myocardial infarction and pre-existing angina as defined above.There were fewer deaths in patients with angina (categories 2 and 3 above) treated with clofibrate than in those on placebo. The mortality in the former group was reduced by 62%, and this is a statistically significant difference. Clofibrate did not have any statistically significant effect in reducing the rate of non-fatal infarction in patients with angina or in those with myocardial infarction and pre-existing angina, though a beneficial trend was evident when both subgroups were combined (a 44% reduction compared with the placebo group). There was a significant reduction in all events (fatal and non-fatal) in patients with angina (“all anginas”) in the clofibrate-treated group; the rate was reduced by 53%.Clofibrate did not alter the overall mortality or morbidity rates in patients admitted to the trial with recent myocardial infarction without preceding angina of more than three months'' duration. In one subgroup there was a statistically significant adverse effect in the clofibrate-treated group. The lack of any overall effect in patients with myocardial infarction might be related to the unexpectedly low mortality rate (2·97%) in the placebo group; it is usually in the region of 4-9% per annum after first myocardial infarction.In patients categorized as “all anginas” there was significant reduction in events whether the initial serum cholesterol level was high (greater than 260 mg/100 ml) or normal. Clofibrate seemed to have a small but not significant beneficial effect in patients with myocardial infarction with initially high serum cholesterol levels, but was of no value in those with initially normal serum cholesterol levels. There was no significant relationship between the response or lack of response of serum cholesterol to clofibrate and the incidence of events either in patients with angina or in those with infarction.The main conclusion of this trial is that clofibrate had a beneficial effect in reducing mortality and, to a lesser extent, morbidity in patients who presented with angina (“all anginas”). This effect was independent of initial serum cholesterol levels or the extent to which serum cholesterol was lowered. The drug had no significant overall effect on prognosis in patients with myocardial infarction alone.     

Myocardial infarction size: measurement and modification

The majority of in-hospital deaths from acute myocardial infarction occur as a result of the “power failure” syndrome (severe congestive heart failure and cardiogenic shock), which results from extensive loss of myocardium. The death of myocardial cells is sequential over many hours. Surrounding the central zone of necrosis in an acute myocardial infarction is a zone of ischemic myocardium whose fate might be altered by interventions during the early phase of the infarction. ST-segment mapping, serial measurement of the serum concentration of creatine phosphokinase and myocardial imaging by means of radionuclides are being developed for the noninvasive assessment of infarct size in animals and humans. A number of interventions appear to limit infarct size in animals. There have been relatively few studies in humans to date, but preliminary results suggest that infarct size might be limited by certain interventions. The research has provided important practical benefits in terms of understanding the course of acute myocardial infarction and the potential effects of conventional therapies. For the present, interventions designed to limit infarct size remain in the realm of clinical research; routine clinical use would be inappropriate.     

Plasma Pentraxin 3 Levels Do Not Predict Coronary Events but Reflect Metabolic Disorders in Patients with Coronary Artery Disease in the CARE Trial

Chronic inflammation closely associates with obesity, metabolic syndrome, diabetes mellitus, and atherosclerosis. Evidence indicates that the immunomodulator pentraxin 3 (PTX3) may serve as a biomarker of these cardiometabolic disorders, but whether PTX3 predicts cardiovascular complications is unknown. We examined the association of plasma PTX3 levels with recurrent coronary events via a prospective, nested, case-control design in the CARE trial. Among 4159 patients who had a prior myocardial infarction 3 to 20 months before enrollment and also had total cholesterol levels <240 mg/dL and LDL cholesterol levels between 115 and 175 mg/dL, we measured plasma PTX3 levels at baseline by high-sensitivity ELISA in 413 cases with recurrent myocardial infarction or coronary death during a 5-year follow-up period, and in 366 sex- and age-matched controls. Cases with recurrent coronary events and controls had similar PTX3 levels, and PTX3 did not predict recurrent coronary events — a finding that contrasts with that of C-reactive protein (CRP) and serum amyloid A (SAA) in this cohort. We then associated PTX3 levels with metabolic disorders. Low plasma PTX3 levels correlated with high body-mass index, waist circumference, and triglycerides; and with low HDL cholesterol. Overall, PTX3 levels correlated inversely with the number of metabolic syndrome components. PTX3 levels also correlated inversely with apoCIII and tissue plasminogen activator, but did not associate with CRP. Although the study further links low PTX3 levels with various features associated with metabolic syndrome, the results do not indicate that PTX3 can predict recurrent coronary events among MI survivors.     

Respiratory Insufficiency in Acute Myocardial Infarction

Arterial blood gases and pH were assessed in 115 patients who had suffered a myocardial infarction, with or without complicating cardiogenic shock or cardiac standstill. In 11 of the 78 uncomplicated cases and in 16 of the 37 complicated cases, the arterial O₂ tension was much lower than would be expected on the basis of a three-fold drop in cardiac output, indicating considerable right to left shunting. The death rate in the patients with uncomplicated myocardial infarction was 32% and that of the complicated cases 65%. In both groups it was greatest when the arterial pH was low, indicating that correction of the acidosis is essential. In many instances administration of 100% oxygen is inadequate to restore the oxygen tension to normal levels, and controlled ventilation may be necessary to maintain adequate alveolar ventilation. The findings indicate the necessity for repeated assessment of the arterial blood gas tensions and pH in any patient who has suffered a myocardial infarction. If the management of such patients is designed to provide adequate oxygenation, to maintain adequate alveolar ventilation and to correct the acid-base disturbances, the patient may be tided over the stage of “cardiac pump failure”.     

Studies of Male Survivors of Myocardial Infarction: XII. Relation of Serum Lipids and Lipoproteins to Survival Over a 10-Year Period

The relation of serum cholesterol and standard S_t lipoproteins to survival over a 10-year period was studied in a “good risk” group of 120 men, aged 31 to 83, who had survived myocardial infarction by at least three months. All subjects were free of other disorders that might affect survival and were not receiving therapy to alter their serum lipids.Ten-year survival from time of entry into the study was 35%. Age had no important influence on survival. Neither the level of the serum cholesterol nor of the lipoprotein fractions related to survival. Mode of coronary death, whether infarctional or sudden, was also unrelated to serum cholesterol.Although the incidence and age of onset of CHD is influenced by serum lipid levels, survival subsequent to infarction is not. Apparently serum lipids affect the rate of atherogenesis in the long silent preclinical stage, but in the short clinical stage other factors determine survival. This suggests that therapy to lower serum lipids, based on a specific diagnosis of the type of hyperlipoproteinemia, should be started early in life before clinical disease occurs.     

Protein Kinase C ε Expression in Platelets from Patients with Acute Myocardial Infarction

Objective

Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C ε (PKCε) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKCε in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKCε with a pathophysiological role in the disease.

Methods and Results

We therefore studied platelet PKCε expression from 24 patients with myocardial infarction, 24 patients with stable coronary artery disease and 24 healthy subjects. Indeed, platelets from myocardial infarction patients expressed PKCε with a significant frequency as compared to both stable coronary artery disease and healthy subjects. PKCε returned negative during patient follow-up. The forced expression of PKCε in normal donor platelets significantly increased their response to adenosine diphosphate-induced activation and adhesion to subendothelial collagen.

Conclusions

Our data suggest that platelet generations produced before the acute event retain PKCε-mRNA that is not down-regulated during terminal megakaryocyte differentiation. Results are discussed in the perspective of peri-infarctual megakaryocytopoiesis as a critical component of myocardial infarction pathophysiology.     

STEMI or non-STEMI: that is the question

Acute coronary syndromes are usually classified on the basis of the presence or absence of ST elevation on the ECG: ST-elevation myocardial infarction or non-ST-elevation myocardial infarction (NSTEMI)patients with acute myocardial infarction (AMI) need immediate therapy, without unnecessary delay and primary percutaneous coronary intervention (PPCI) should preferably be performed within 90 min after first medical contact. However, in AMI patients without ST-segment elevation (pre) hospital triage for immediate transfer to the catheterisation laboratory may be difficult. Moreover, initial diagnosis and risk stratification take place at busy emergency departments and chest pain units with additional risk of ‘PPCI delay’. Optimal timing of angiography and revascularisation remains a challenge. We describe a patient with NSTEMI who was scheduled for early coronary angiography within 24 h but retrospectively should have been sent to the cath lab immediately because he had a significant amount of myocardium at risk, undetected by non-invasive parameters.     

Myocardial Revascularization in High-Risk Coronary Patients

It is recognized that postoperative mortality, infarction and the need for inotropic support are increased following myocardial revascularization in highrisk patients. Operations were carried out in 57 such patients in whom one or more of the following factors were present: ventricular dysfunction—ejection fraction less than 0.4 (17), unstable (8) or preinfarction angina (29), evolving infarction (8), recent infarction (less than two weeks before) (5) and refractory ventricular tachyarrhythmia (4). Combined risk factors were present in nine patients. The following principles were utilized to minimize ischemic injury: (1) avoidance of prebypass hypertension and hypotension, (2) avoidance of extreme hemodilution, (3) avoidance of ventricular fibrillation, (4) maintenance of beating empty heart, when possible, (5) the limiting of ischemic periods to less than 12 minutes (hypothermia 32°C) and (6) repaying myocardial oxygen debt with total (vented) bypass, when necessary. The following results were obtained: inotropic support was required in five patients (9 percent), “new” postoperative infarction occurred in five patients (9 percent) and one patient died (2 percent). These results are comparable to those reported in good-risk patients, and indicate that optimal myocardial protection will allow safe revascularization in a high-risk patient.     

Independence of the Sodium and Potassium Conductance Channels: A Kinetic Argument

Tightly coupled models for the sodium and potassium conductance changes, in which the potassium “on” process is intimately related to the sodium “on” and “off” processes, are studied. It is shown that such coupled models are incapable of simultaneously showing the observed effects of conditioning potentials on sodium inactivation and on the translation of the potassium conductance in time. It is concluded that the primary mechanisms for the sodium and potassium channels are probably independent.