S. Richard Underwood

Management of acute myocardial infarction in patients presenting with ST-segment elevation

Summary: initial diagnosis of acute myocar-dial infarction •History of chest pain/discomfort.•ST-segment elevations or (presumed) new leftbundle-branch block on admission ECG. RepeatedECG recordings often needed.•Elevated markers of myocardial necrosis (CK-MB,troponins). One should not wait for the results toinitiate reperfusion treatment!•2D echocardiography and perfusion scintigraphyhelpful to rule out acute myocardial infarction. Relief of pain, breathlessness and anxiety Relief of pain is of paramount importance, not onlyfor humane reasons but because the pain is associ-ated with sympathetic activation which causesvasoconstriction and increases the workload of theheart. Intravenous opioids—morphine or, whereavailable, diamorphine—are the analgesics mostcommonly used in this context (e.g. 4 to 8 mgmorphine with additional doses of 2 mg at intervalsof 5 min until the pain is relieved); intramuscularinjections should be avoided. Repeated dosesmay be necessary. Side effects include nausea andvomiting, hypotension with bradycardia, andrespiratory depression. Antiemetics may be admin-istered concurrently with opioids. The hypotensionand bradycardia will usually respond to atropine,and respiratory depression to naloxone, whichshould always be available. If opioids fail to relievethe pain after repeated administration, intra-venous beta-blockers or nitrates are sometimeseffective. Oxygen (2– 4l.min

Magnetic resonance imaging during dobutamine stress in coronary artery disease

Cine magnetic resonance imaging (MRI) provides a tomographic method of assessing regional ventricular function in any desired plane. It has not been possible to obtain adequate images during dynamic exercise, and this has limited its value in patients with coronary artery disease (CAD). Therefore, an infusion of dobutamine was used to study 25 patients with exertional chest pain and abnormal exercise electrocardiograms. Areas of abnormal wall motion were compared with areas of abnormal myocardial perfusion imaged by dobutamine thallium emission tomography and with coronary arteriography. Twenty-two patients had significant CAD. Twenty-one (96%) of these patients had reversible myocardial ischemia shown by dobutamine thallium tomography, and 20 (91%) had reversible wall motion abnormalities shown by dobutamine MRI. Comparison of abnormal segments of perfusion and wall motion showed 96% agreement at rest, 90% agreement during stress, and 91% agreement for the assessment of functional reversibility. The normalized magnetic resonance signal intensity of the ischemic segments showed a small but significant reduction when compared with that of normal segments (-67 units [9.2%]; p less than 0.05). Dobutamine infusion was well-tolerated, despite causing chest discomfort in 24 patients (96%). Nine patients (36%) developed a minor dysrhythmia that was usually ventricular premature complexes, but this did not limit infusion, and other side effects were mild. The short plasma half-life of dobutamine makes it ideal as a stress agent for imaging techniques (such as MRI), and these results suggest that it is more effective in the provocation of wall motion abnormalities than is dipyridamole in patients with CAD.

Effects of Age, Gender, Obesity, and Diabetes on the Efficacy and Safety of the Selective A2A Agonist Regadenoson Versus Adenosine in Myocardial Perfusion Imaging: Integrated ADVANCE-MPI Trial Results

OBJECTIVES To compare the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson stress myocardial perfusion imaging, and to assess the noninferiority of regadenoson to adenosine for the detection of reversible myocardial perfusion defects. BACKGROUND Previous reports have shown that a fixed unit bolus of regadenoson is safe and noninferior to adenosine for the detection of reversible perfusion defects by radionuclide imaging. METHODS Using a database of 2,015 patients, we evaluated the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson compared to adenosine. RESULTS For detection of ischemia relative to adenosine, noninferiority was demonstrated for all patients (agreement rate difference 0%, 95% CI -6.2% to +6.8%). The average agreement rate between adenosine-adenosine and adenosine-regadenoson were 0.62 +/- 0.03 and 0.63 +/- 0.02. Detection of ischemia was also comparable in specific subgroups. Agreement was less for both agents in women versus men with moderate and large areas of ischemia. Compared to adenosine, regadenoson had a lower combined symptom score and less chest pain, flushing, and throat, neck, or jaw pain, but more headache and gastrointestinal discomfort. This was true in nearly all subgroups. Regadenoson patients reported feeling more comfortable (1.7 +/- .02 vs. 1.9 +/- 0.03, p < 0.001). Based on the overall tolerability score, women felt less comfortable than men with both stress agents. Image quality was rated good or excellent in 92% for both agents. CONCLUSIONS Regadenoson can be safely administered as a fixed unit bolus and is as efficacious as adenosine in detecting ischemia regardless of age, gender, body mass index, and diabetes. Regadenoson is better tolerated overall and across various subgroups.

Pulmonary artery distensibility and blood flow patterns: A magnetic resonance study of normal subjects and of patients with pulmonary arterial hypertension

Abstract Pulmonary artery distensibility was studied with spin-echo magnetic resonance imaging in 20 normal subjects of variable age and in four patients with pulmonary arterial hypertension. The distensibility was found to be significantly lower (8%) in patients with pulmonary arterial hypertension than it was in normal subjects (23%). No age-related difference occurred. Magnetic resonance velocity mapping of the pulmonary artery blood flow was performed in 26 normal subjects—11 had mapping in the mid pulmonary artery, 15 had mapping in the distal pulmonary artery, and mapping in the four patients with pulmonary arterial hypertension was in the mid pulmonary artery. The pulmonary artery flow volume was compared with aortic flow and left ventricular stroke volume and a very good correlation was found. A retrograde flow of 2% occurred in the normal subjects serving to close the pulmonic valve. Antegrade plug flow occurred in most normal subjects but varied among individuals. There were also other variations in the flow pattern among normal individuals. All patients with pulmonary arterial hypertension had a markedly irregular ante- and retrograde flow and a large retrograde flow (average 26%). Magnetic resonance imaging offers a noninvasive way to evaluate pulmonary arterial hypertension as well as to quantitate pulmonary and aortic flows in, for example, left-to-right shunts.

Dobutamine thallium myocardial perfusion tomography

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Type 1 Diabetes Mellitus on the Gender Difference in Coronary Artery Calcification

OBJECTIVES To examine whether the gender difference in coronary artery calcification, a measure of atherosclerotic plaque burden, is lost in type 1 diabetic patients, and whether abnormalities in established coronary heart disease risk factors explain this. BACKGROUND Type 1 diabetes abolishes the gender difference in coronary heart disease mortality because it is associated with a greater elevation of coronary disease risk in women than men. The pathophysiological basis of this is not understood. METHODS Coronary artery calcification and coronary risk factors were compared in 199 type 1 diabetic patients and 201 nondiabetic participants of similar age (30 to 55 years) and gender (50% female) distribution. Only one subject had a history of coronary disease. Calcification was measured with electron beam computed tomography. RESULTS In nondiabetic participants there was a large gender difference in calcification prevalence (men 54%, women 21%, odds ratio 4.5, p < 0.001), half of which was explained by established risk factors (odds ratio after adjustment = 2.2). Diabetes was associated with a greatly increased prevalence of calcification in women (47%), but not men (52%), so that the gender difference in calcification was lost (p = 0.002 for the greater effect of diabetes on calcification in women than men). On adjustment for risk factors, diabetes remained associated with a threefold higher odds ratio of calcification in women than men (p = 0.02). CONCLUSIONS In type 1 diabetes coronary artery calcification is greatly increased in women and the gender difference in calcification is lost. Little of this is explained by known coronary risk factors.

Adenosine combined with dynamic exercise for myocardial perfusion imaging

OBJECTIVES This study investigated whether combining exercise with adenosine would reduce the adverse effects of adenosine vasodilation. BACKGROUND Adenosine vasodilation is effective for perfusion imaging but causes frequent unpleasant noncardiac adverse effects, high noncardiac tracer uptake and occasional arrhythmias. METHODS Of 500 consecutive patients referred for thallium-201 myocardial perfusion imaging, 407 were randomized to three study groups: 6 min of adenosine infusion alone; 6 min of adenosine with submaximal exercise; or symptom-limited exercise with continuous adenosine. Minimal detectable differences are presented; a significance level of 0.05 with a power of 80% is assumed. RESULTS There was no difference among the three groups in sensitivity and specificity (overall 96% and 78%, minimal detectable differences 5.5% and 11%, respectively) for detection of coronary artery disease or stenosis in individual coronary arteries. There was a trend toward improved sensitivity in the combined exercise groups compared with that in the adenosine-only group (98% vs. 93%, p = 0.07, minimal detectable difference 6%). Noncardiac side effects were reduced by 43% in the exercise groups (p < 0.0001), and major arrhythmias were reduced by 90% (p < 0.0001). There was no effect on minor arrhythmias (25% vs. 22%, p = 0.6, minimal detectable difference 12%). The heart/background ratios were higher in the exercise groups (all p < 0.02). Each ratio was correlated with the exercise level achieved (all p < 0.001). The reversibility score increased with exercise (p = 0.04), as did the number of patients and segments with reversible defects (both p = 0.03). CONCLUSIONS Combining exercise with adenosine infusion reduced the noncardiac side effects of vasodilation and major arrhythmias while improving redistribution and heart/background ratios. These findings may be clinically important. Although maximal exercise with adenosine infusion produced optimal results, the improvement over the submaximal exercise protocol was minor, and this has the advantage of being simple and achievable within the normal 6-min duration of the adenosine infusion.

Quantitation of antegrade and retrograde blood flow in the human aorta by magnetic resonance velocity mapping

Magnetic resonance velocity mapping was used in 24 normal subjects to study two-dimensional velocity profiles in the proximal and mid-ascending aorta, and to quantify both forward and reverse flow. The aortic flow measurements were validated by comparison with left ventricular stroke volume in all subjects and by comparison with pulmonary flow measurements in 12. Agreement was good with standard errors of the estimate of 7.8 and 7.1 ml, and correlation coefficients of 0.93 and 0.95, respectively. Systolic velocity maps were similar in the proximal aorta and the mid-ascending aorta, with maximum early systolic flow along the left posterior wall. Toward the end of systole and throughout diastole, a channel of reverse flow developed in the same region in the mid-ascending aorta, but in the proximal aorta it split to enter the sinuses of Valsalva, predominantly the left and the right coronary sinuses. Mean percentage ratio of retrograde-to-antegrade flow was 6.3%, with the majority of retrograde flow occurring in early diastole. The findings suggest that the retrograde flow is related to coronary artery flow and it is possible that aortic disease, which is known to influence aortic flow patterns, may also influence coronary flow.

Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy.

BACKGROUND AND PURPOSE To evaluate radiation-induced defects in myocardial perfusion imaging in early breast cancer patients treated with modern technique radiotherapy. PATIENTS AND METHODS Twenty-four patients with left-breast tumours and 12 control patients with right-breast tumours, relapse-free since treatment for primary disease, who had undergone radiotherapy at least 5 years previously and with no history of ischaemic heart disease prior to radiotherapy underwent study. In left-breast patients, at least 1 cm of heart was required to have been in the treatment field. Patients underwent cardiac assessment and single photon emission computerized tomography myocardial perfusion imaging. RESULTS Myocardial perfusion tracer uptake was abnormal in 17 (70.8%) left-breast and two (16.7%) right-breast patients (P = 0.002). Of the 17 abnormal scans in left-breast patients, abnormalities were confined to the cardiac apex in 16 patients, and perfusion defects were reversible (n = 7), fixed (n = 7) or mixed (n = 3). Reversible perfusion defects that were not confined to the cardiac apex were observed in two right-breast patients. Left ventricular ejection fraction was normal in all 33 patients in whom it was measured, and no myocardial perfusion abnormalities were judged to require treatment or follow-up. CONCLUSIONS In this selected study population modern technique radiotherapy to the left breast was associated with a significantly greater number of myocardial perfusion abnormalities than radiotherapy to the right breast. These abnormalities were both reversible and irreversible, suggesting that radiotherapy can lead to both myocardial damage and to epicardial coronary disease. With a minimum of 5 years follow-up since treatment, no abnormalities were considered to be clinically significant.

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

Background—The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results—A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ⩽0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69–0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65–0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). Conclusions—In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.