Randomized Trial of Primary PCI with or without RoutineManual Thrombectomy

During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.

Comparison of left ventricular performance in healthy young women and men during exercise.

BACKGROUND: Previous studies show sex-related differences in left ventricular (LV) response to exercise. It is not clear, however, whether these differences are also seen in younger healthy subjects. METHODS AND RESULTS: This study examined the changes in LV performance during dynamic upright exercise in 11 healthy men and 19 healthy young women according to the Bruce protocol and an individualized ramp protocol. There were no significant differences between the two protocols for either men or women in heart rate, blood pressure, LV ejection fraction (EF) (measured by ambulatory nuclear detector), and measured oxygen consumption. The peak oxygen consumption was higher in men than in women (44 +/- 13 vs 36 +/- 9 ml/kg/min; p < 0.05), but the peak heart rate, systolic blood pressure, and EF were similar. The change in EF (from rest to exercise) was 19% +/- 8% in men and 19% +/- 11% in women with the Bruce protocol (difference not significant) and 26% +/- 9% in men and 19% +/- 6% in women with the ramp protocol (difference not significant). At peak exercise, both men and women showed an increase in end-diastolic volume (29% +/- 14% vs 23% +/- 11%; difference not significant) and a decrease in end-systolic volume (41% +/- 15% vs 43% +/- 21%) (difference not significant). The increase in cardiac output during exercise was due to an increase in heart rate and stroke volume in both men and women. At submaximal exercise, however, the decrease in end-systolic volume was less in women than in men (p < 0.05). CONCLUSIONS: There are no sex-related differences in compensatory mechanism during dynamic exercise in healthy subjects. The changes in contractility and LV volume are not affected by the exercise protocol.

Results of adenosine single photon emission computed tomography thallium-201 imaging in hemodynamic nonresponders.

Systolic blood pressure typically decreases during adenosine infusion because of stimulation of A2b receptors, resulting in systemic vasodilation. This study examined the results of adenosine single photon emission computed tomography (SPECT) thallium-201 imaging in patients who did not show such a decrease in blood pressure during peak adenosine effect (nonresponders). The 102 nonresponders and 341 responders had no significant differences in age, gender, history of diabetes mellitus, hypertension, or previous myocardial infarction. The extent of coronary artery disease (CAD) by angiography was also similar. The sensitivity of SPECT thallium-201 imaging in patients with one-vessel disease was 82% in nonresponders and 84% in responders (p value not significant [NS]); in patients with multivessel disease, it was 90% in nonresponders and 94% in responders (p = NS) and for all CAD, it was 87% in non-responders and 91% in responders (p = NS). Thus lack of hemodynamic systemic response during adenosine infusion does not affect sensitivity for detecting CAD.

Impact on exercise single-photon emission computed tomographic thallium imaging on patient management and outcome.

BACKGROUND: Stress perfusion imaging is useful in risk stratification of patients with known or suspected coronary artery disease. In the current era of managed health care, there is a need to provide data on patient outcome. METHODS AND RESULTS: This study examined the impact of exercise single-photon emission computed tomographic (SPECT) thallium imaging on patient management (the subsequent need for coronary angiography and revascularization) and outcome (the occurrence of hard cardiac events defined as cardiac death or nonfatal acute myocardial infarction) in 2700 patients who were being evaluated for diagnostic purposes. None of the patients had previous coronary angiography, coronary revascularization, or Q-wave myocardial infarction. The SPECT images were normal in 2027 patients (group 1) and abnormal in 673 patients (group 2). Within 6 months after thallium imaging 53 patients in group 1 (3%) and 242 patients in group 2 (36%) underwent coronary angiography (p = 0.0001). The patients who underwent coronary angiography had higher pretest probability of coronary disease (group 1) or more perfusion defects (group 2) than patients who did not (p = 0.0001 each). Coronary revascularization within 3 months of coronary angiography was performed in 1 of the 53 patients (2%) in group 1 and in 87 of 242 patients (30%) in group 2 (p = 0.0001). Among the remaining patients who had coronary angiography but were medically treated there were no hard cardiac events in group 1 but there were 15 events in group 2 (p = 0.02). CONCLUSIONS: The results of exercise SPECT thallium imaging are important in patient management and outcome. Coronary angiography, coronary revascularization and events are rare in patients with normal exercise SPECT thallium images.

Circadian variation of ventricular arrhythmia recurrences after cardioverter-defibrillator implantation in patients with healed myocardial infarcts.

Past studies using Holter monitoring and retrospective reviews of death certificates have documented peak occurrence of sudden death and nonsustained ventricular tachycardia (VT) in the morning hours. We used the Ventritex Cadence device (Ventritex, Sunnyvale, California) which documents the date and time of all stored arrhythmias leading to device therapy to evaluate the circadian pattern of sustained ventricular arrhythmia recurrence. Mean follow-up after defibrillator implantation was 628 +/- 285 days. All 390 patients had at least 1 episode (range 1 to 43) of sustained VT documented from analysis of the stored electrograms associated with an arrhythmia event. Stored electrograms were available for review and analysis in 3,041 device detections; 349 stored events were excluded because they did not fulfill the diagnostic criteria for VT or failed to document the onset of the ventricular arrhythmia at the beginning of the recorded event of the arrhythmia episode. Criteria for the diagnosis of VT or ventricular fibrillation were met in 2,692 arrhythmia episodes occurring in 390 patients. There was circadian variation for ventricular arrhythmia recurrence for the whole patient group with the data fit to the sinusoidal density function: f(t) = 126 - 51 x cos (-57 + 2 pi t/24) - 25 x sin (63 + 2 pi t/12) (p < 0.0001). Ventricular arrhythmia occurrence rate was lowest between 2:00 and 3:00 A.M., and highest between 10:00 and 11:00 A.M. In addition, the same circadian pattern was demonstrated regardless of patient age, gender, left ventricular ejection fraction (< 35% or > or = 35%), and VT cycle length (< 300 or > or = 300 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between diastolic left ventricular function and myocardial blood volume during adenosine-induced coronary hyperemia.

Adenosine infusion is accompanied by increases in coronary blood flow and myocardial blood volume. Myocardial blood volume may produce changes in diastolic left ventricular (LV) performance by increasing myocardial turgor. Diastolic dysfunction may also be the result of myocardial ischemia. The relation between changes in LV mass and diastolic function has not been previously investigated. This study examined the relation between changes in LV mass during adenosine-induced coronary hyperemia and LV diastolic function. Serial two-dimensional and Doppler echocardiographic measurements were made before, during, and after adenosine infusion (140 micrograms/min for 6 min) in 21 patients with (group 1) and 10 patients without (group 2) coronary artery disease (CAD). The LV mass and transmitral diastolic filling indexes were determined from digitized images from apical four-chamber view. Adenosine infusion produced a greater increase in LV mass in group 2 than in group 1 (29% +/- 11% vs 9% +/- 6%, p < 0.0002). The ratio of transmitral early (E) to atrial (A) filling velocity (E/A) increased 10% +/- 16% in group 2 and decreased 8% +/- 20% in group 1 (p < 0.02), and the velocity time integral of early filling increased 11% +/- 52% in group 2 and decreased 20% +/- 31% in group 1 (p < 0.04). There was a correlation between the change in E/A ratio and the LV mass (r = 0.53, p < 0.003). Thus adenosine infusion caused a greater increase in LV mass in normal subjects than in patients with CAD. There were also changes in Doppler-derived indexes of diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent and incremental prognostic value of exercise thallium single-photon emission computed tomographic imaging in women.

BACKGROUND: This study examined the independent and incremental prognostic value of exercise thallium single-photon emission computed tomographic imaging in 212 women who also underwent coronary angiography. METHODS AND RESULTS: The left ventricular ejection fraction was normal (65% +/- 15%). During a mean follow-up of 40 months, 27 women had events (cardiac death or nonfatal myocardial infarction). Univariate Cox survival analysis showed several variables to be different between patients with events and those without events: age, exercise heart rate, the extent of coronary artery disease, reversible thallium defects, number of segments with reversible abnormality, and size of perfusion abnormality. Multivariate survival analysis showed that a large perfusion abnormality and age were the independent predictors of events. Actuarial life-table analysis showed that women with a large thallium abnormality (> or = 15% of the myocardium) had significantly worse event-free survival rates than had women with no or small abnormalities (Mantel-Cox statistic = 16; p = 0.0001). CONCLUSIONS: Thus exercise thallium-201 single-photon emission computed tomographic imaging provides independent and incremental prognostic information to clinical, exercise, and coronary angiographic results in women. The presence of a larger thallium abnormality identifies women at high risk of cardiac events.

Serial changes in left ventricular function after coronary artery bypass: implications in viability assessment.

Improvement in left ventricular (LV) performance after coronary artery bypass surgery remains the gold standard in myocardial viability assessment. The time-related changes, however, are not well known. This study examined the LV ejection fraction (EF) by gated blood pool imaging early (6 +/- 4 days) and late (62 +/- 24 days) after surgery in patients with normal preoperative EF (group 1, n = 12) and those with LV dysfunction (group 2, n = 15). There were no changes in the clinical status between the early and late studies, and all patients had normal sinus rhythm. Group 1 had no significant change in EF (preoperatively 62%, early postoperatively 64%, late postoperatively 63%; p = NS). In group 2, EF was 26% +/- 8% preoperatively; 30% +/- 10% early postoperatively; and 34% +/- 8% late postoperatively (p < 0.05). Postoperatively there was > or = 5% improvement in EF in 4 patients early and 11 patients late (p < 0.05). Patients who showed early improvement continued to do so in the late study but, additionally, 7 patients showed improvement only in the late study. Thus the timing of EF measurement after surgery is important in patients with LV dysfunction but not in patients with normal LV function. Early assessment may underestimate the prevalence and degree of recovery.

Prognostic implications of normal exercise tomographic thallium images in patients with angiographic evidence of significant coronary artery disease.

This study examines the prognostic implications of normal exercise tomographic thallium images in medically treated patients with angiographic evidence of coronary artery disease (CAD). There were 97 patients aged 60 +/- 10 years; 52 had 1-, 30 had 2-, and 15 had 3-vessel CAD (> or = 50% diameter stenosis). The exercise test was submaximal in 51 patients (53%); ST-segment depression during exercise occurred in 20 patients (21%), and angina during exercise occurred in 23 patients (24%). Most patients (71%) were receiving antianginal therapy. During a mean follow-up of 32 months, only 3 patients had cardiac events: 2 died of cardiac causes and 1 had nonfatal myocardial infarction (event rate 1.1%/year). None of those 3 patients had positive ST response during exercise. Thus, medically treated patients with CAD (including those with multivessel CAD) have a benign prognosis in the presence of normal exercise thallium images. These results have important implications in patient management and cost of health delivery.

Prognostic significance of silent ischemia.

This study examined the prognostic predictors in 521 patients with angiographic evidence of coronary artery disease (CAD). All patients underwent exercise single-photon emission computed tomographic thallium imaging. The patients were divided into those with symptomatic ischemia defined as reversible thallium defects, S-T segment depression (or both) and angina during exercise (n = 210, group 1), and silent ischemia defined as thallium defects or ST segment depression (or both) but no angina during exercise (n = 311, group 2). During a mean follow-up of 24 +/- 21 months, there were 30 cardiac events (death or nonfatal myocardial infarction). The extent of CAD (2.0 +/- 0.8 diseased vessels in group 1 and 2.1 +/- 0.8 diseased vessels in group 2), the left ventricular ejection fraction, the extent of perfusion abnormality (21% +/- 11% in group 1 and 24% +/- 12% in group 2), and the peak heart rate and double product were similar in the two groups. Survival analysis showed no significant difference in the event-free survival in patients with symptomatic or silent ischemia. The 2-year event-free survival rate was 95% in group 1 and 94% in group 2 (difference not significant). The extent of perfusion abnormality and history of diabetes mellitus were the most important predictors of events. Thus the prognosis of medically treated patients with CAD is comparable in those patients with silent or symptomatic ischemia and is dependent on the extent of myocardium at risk rather than presence or absence of angina pectoris during exercise.

Prognostic value of adenosine single-photon emission computed tomographic thallium imaging in medically treated patients with angiographic evidence of coronary artery disease.

BACKGROUND: This study examined the prognostic value of adenosine single-photon emission computed tomographic thallium imaging in medically treated patients with angiographic evidence of coronary artery disease (CAD). METHODS AND RESULTS: Patients who underwent coronary revascularization within 3 months of this study were excluded. There were 177 patients aged 64 +/- 11 years; 74 had one-vessel, 57 had two-vessel, and 46 had three-vessel CAD (> or = 50% diameter stenosis). During a mean follow-up of 22 +/- 13 months, there were 14 events (cardiac death or nonfatal myocardial infarction). Cox survival analysis with important clinical, catheterization, and scintigraphic variables identified the size of perfusion abnormality as the strongest predictor of events (chi 2 = 9). Life-table analysis showed that patients with perfusion defects of 15% or greater of the myocardium had a worse prognosis than had patients with no or smaller defects (Mantel-Cox statistic = 13; p < 0.001). CONCLUSIONS: Thus adenosine single-photo emission computed tomographic thallium imaging provides important prognostic data in medically treated patients with CAD. The extent of thallium abnormality is the most important predictor of events.

Doppler echocardiographic evaluation of the spectrum of left ventricular diastolic dysfunction in essential hypertension.

Left ventricular topography and diastolic and systolic functions were studied in 41 patients with essential hypertension (group 1) and 33 age-matched normal adults (group 2) by Doppler echocardiography. In group 1 54% had LV concentric hypertrophy, 19% had combined concentric hypertrophy and eccentric remodeling, and 27% had concentric remodeling. LV systolic function was within the normal range. In concentric LV remodeling, the EDV was significantly decreased (compared with group 2) (84 +/- 15 vs 130 +/- 38 ml, p < 0.05), whereas the NPFR was normal (2.89 +/- 0.65 vs 3.22 +/- 0.83 sec-1, p = NS). In concentric hypertrophy, LV end-diastolic and end-systolic volumes were normal, but the NPFR was decreased (2.04 +/- 0.59 sec-1). Patients with concentric hypertrophy and eccentric remodeling had the largest end-diastolic (140 +/- 48 ml) and end-systolic (62 +/- 32 ml) volumes and the lowest NPFR (1.67 +/- 0.69 sec-1). The LVMI inversely correlated with the NPFR (r = -0.89, p < 0.0001). Thus LV concentric hypertrophy with or without concentric or eccentric remodeling is seen in patients with systemic hypertension. A decrease in peak filling occurs early in the evolution of hypertensive heart disease and is observed even when systolic performance is still normal.

Study of myocardial infarct remodeling by single-photon emission computed tomographic imaging.

Left ventricular (LV) remodeling after Q-wave anterior acute myocardial infarction (AMI) was examined with single-photon emission computed tomographic thallium imaging. Initial (after adenosine infusion) and 4-hour delayed reinjection images were obtained in 34 patients aged 65 +/- 12 years. Short-axis slices from the delayed images were quantitatively analyzed by measuring the outer and inner diameters, and wall thickness. The results were compared with those in a group of normal subjects. The outer diameter was greater in patients than in normal subjects at the apical, mid- and basal levels (all p < 0.01); the average outer diameter was 16.9 +/- 1.9 mm in patients, and 12.2 +/- 1.3 mm in normal subjects (p < 0.001). Similarly, the inner diameter was greater in patients than in normal subjects at the 3 levels (all p < 0.05); the average inner diameter was 6.5 +/- 1.8 mm in patients, and 4.7 +/- 1.3 mm in normal subjects (p < 0.01). Wall thickness was greater in patients than in normal subjects (5.2 +/- 0.5 vs 3.8 +/- 0.5 mm; p < 0.0001). There were significant correlations between LV dilation and time elapsed (in weeks) since AMI (r = 0.57; p < 0.005), and the size of the perfusion abnormality (r = 0.44; p < 0.03). Thus, LV dilation occurs after Q-wave anterior AMI, and is related to infarct size and duration. These changes can be studied by single-photon emission computed tomographic thallium imaging.

Microbial esterase detection with ultraviolet fluorescence.

A method is presented to identify esterase-synthesizing microbial colonies within mixed culture plates by utilizing induced esterase hydrolysis of nonfluorescent butyryl ester of 7-hydroxy-4-methylcoumarin to the highly fluorescent 7-hydroxy-4 methyl umbelliferone. Microscopy procedures for making esterase loci of fungal mycelia visible with this reaction are described.