Zuo Xiang He

Identification of Patients at Increased Risk of First Unheralded Acute Myocardial Infarction by Electron-Beam Computed Tomography

BACKGROUND There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS. METHODS AND RESULTS We conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32+/-7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53+/-8 versus 52+/-9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group). CONCLUSIONS Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.

Severity of Coronary Artery Calcification by Electron Beam Computed Tomography Predicts Silent Myocardial Ischemia

BACKGROUND Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. METHODS AND RESULTS Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS <10 had an abnormal SPECT compared with 2.6% of those with scores from 11 to 100, 11.3% of those with scores from 101 to 399, and 46% of those with scores >/=400 (P<0.0001). CACS predicted an abnormal SPECT regardless of subject age or sex. CONCLUSIONS CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: Relation to rest-redistribution Tl-201 tomography and dobutamine stress echocardiography

OBJECTIVES The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy. BACKGROUND Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later. RESULTS Global wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Assessment of Myocardial Viability With 99mTc Sestamibi in Patients Undergoing Cardiac Transplantation A Scintigraphic/Pathological Study

BACKGROUND 99mTc sestamibi and 201 Tl are tracers that allow equivalent detection of myocardial infarction. However, because sestamibi does not undergo as much time-dependent redistribution as does 201Tl, it has been considered suboptimal for the detection of myocardial viability. METHODS AND RESULTS Fifteen consecutive patients with ischemic cardiomyopathy who underwent orthotopic cardiac transplantation received an intravenous injection of 99mTc sestamibi at 1 to 6 hours before transplantation. Rotational tomography of the excised, intact, native hearts was performed to quantify the extent of myocardial hypoperfusion. The hearts were then sliced and reimaged on a gamma camera, followed by pathological quantification of the extent and severity of scarred and normal myocardium. Samples of normally and abnormally perfused myocardium underwent gamma well counting to determine tissue radioactivity and were examined under light microscopy for delineation of myocardial structure after trichrome staining. The mean extent of scintigraphic scar quantified through the use of rotational tomography was 45 +/- 14% of the left ventricle and correlated closely with pathological scar size (r = .89), despite a slight overestimation. Scintigraphic scar size determined with planar imaging of the individual myocardial slices also correlated closely with pathological scar size (r = .88). A good correlation existed between tissue 99mTc sestamibi activity determined through well counting and histological evidence of myocardial viability (r = .89). Most hypokinetic and 40% of akinetic/dyskinetic myocardial segments contained scintigraphically and histologically normal myocardium. CONCLUSIONS 99mTc sestamibi scintigraphy can be used to accurately quantify the extent of myocardial scarring. Furthermore, the relative sestamibi activity in perfusion defects, measured several hours after administration, is a good indicator of myocardial viability determined with microscopy.

Intensive Medical Therapy Versus Coronary Angioplasty for Suppression of Myocardial Ischemia in Survivors of Acute Myocardial Infarction A Prospective, Randomized Pilot Study

BACKGROUND Patients who have inducible ischemia after acute myocardial infarction (AMI) generally undergo coronary angiography with the intent to revascularize. Whether this approach is superior to intensive treatment with anti-ischemic medications is unknown. METHODS AND RESULTS We performed a prospective, randomized pilot study comparing intensive medical therapy with coronary angioplasty (PTCA) for suppression of myocardial ischemia in 44 stable survivors of AMI. Myocardial ischemia was quantified with adenosine 201Tl tomography (SPECT) performed 4.5+/-2.9 days after AMI. All patients at baseline had a large total (>/=20%) and ischemic (>/=10%) left ventricular perfusion defect size (PDS). SPECT was repeated at 43+/-26 days after therapy was optimized. The total stress-induced PDS was comparably reduced with medical therapy (from 38+/-13% to 26+/-16%; P<0.0001) and PTCA (from 35+/-12% to 20+/-16%; P<0.0001). The reduction in ischemic PDS was also similar (P=NS) in both groups. Cardiac events occurred in 7 of 44 patients over 12+/-5 months. Patients who remained clinically stable had a greater reduction in ischemic PDS (-13+/-9%) than those who had a recurrent cardiac event (-5+/-7%; P<0.02). Event-free survival was superior in the 24 patients who had a significant (>/=9%) reduction in PDS (96%) compared with those who did not (65%; P=0.009). CONCLUSIONS In this small pilot study, intensive medical therapy and PTCA were comparable at suppressing ischemia in stable patients after AMI. Sequential imaging with adenosine SPECT can track changes in PDS after anti-ischemic therapies and thereby predict subsequent outcome. Corroboration of these preliminary findings in a larger cardiac-event trial is warranted.

Assessment of Myocardial Viability With 99mTc-Sestamibi Tomography Before Coronary Bypass Graft Surgery Correlation With Histopathology and Postoperative Improvement in Cardiac Function

BACKGROUND Assessment of myocardial viability by 99mTc-sestamibi remains controversial. Accordingly, we investigated the use of sestamibi as a marker of myocardial viability, defined by histopathology, and for predicting improvement of myocardial function after coronary artery bypass graft surgery (CABG). METHODS AND RESULTS 99mTc-sestamibi perfusion tomography and radionuclide angiography were performed within 2 days before CABG in 21 patients with > or = 75% stenosis of the left anterior descending coronary artery and resting anterior wall dyssynergy. During CABG, transmural myocardial biopsies were obtained from the dyssynergic anterior wall and from normal myocardial segments to determine the extent of viable myocardium by histopathology. Improvement of regional left ventricular function was evaluated by radionuclide angiography at 6 to 8 weeks after CABG. There was a good correlation (r=.85, P<.001) between the quantified sestamibi activity and the extent of viable myocardium determined morphometrically. Among 21 biopsied dyssynergic myocardial segments, 11 improved their function after CABG and 10 failed to improve. Biopsied segments with improved postoperative function had significantly higher sestamibi activity (81+/-5% versus 49+/-16%, P<.0001) and significantly lower extent of interstitial fibrosis (7+/-4% versus 31+/-21%, P=.0002) than segments that failed to improve. A 55% threshold of 99mTc-sestamibi activity had positive and negative predictive values of 79% and 100%, respectively, for recovery of function after CABG in the biopsied segments. CONCLUSIONS Myocardial 99mTc-sestamibi activity correlates well with the extent of viable myocardium and predicts improvement in regional function after CABG. This lends support to the use of sestamibi as a myocardial viability agent.

Evaluation of left ventricular wall motion, volumes, and ejection fraction by gated myocardial tomography with technetium 99m-labeled tetrofosmin: A comparison with cine magnetic resonance imaging

BackgroundWhether left ventricular function can be assessed accurately by gated single photon emission computed tomography (SPECT) in patients with myocardial infarction and severe perfusion defects is not well known.Methods and ResultsTwenty-five patients with an acute myocardial infarction underwent 99mTc-labeled tetrofosmin (99mTc-tetrofosmin) gated SPECT and cine magnetic resonance imaging (MRI). Wall motion was assessed in 13 left ventricular segments using a 5-point scoring system ranging from 3 (normal) to-1 (dyskinetic). Exact agreement for wall motion scores between gated SPECT and MRI was excellent (92%, kappa=0.82). Furthermore, correlations between the two techniques were also good for end-diastolic volume (r=0.81, P<.0001), end-systolic volume (r=0.92, P<.0001), and ejection fraction (r=0.93, P<.0001).ConclusionIn patients with a recent myocardial infarction, 99mTc-tetrofosmin gated SPECT provides reliable evaluation of global and regional ventricular function and volumes.

Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

OBJECTIVES This study was undertaken to evaluate the ability of myocardial contrast echocardiography (MCE) to guide the targeted delivery of ethanol during nonsurgical septal reduction therapy (NSRT) and to assess the relation between the MCE risk area and infarct size determined by enzymatic and radionuclide methods. BACKGROUND NSRT with intracoronary ethanol is a new promising treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). Proper localization and quantification of the septal infarct before ethanol injection are highly desirable. MCE can provide accurate delineation of the vascular territory of the coronary arteries. METHODS Twenty-nine patients with HOCM and maximal medical therapy underwent NSRT. The left ventricular outflow tract (LVOT) gradient by Doppler echocardiography at baseline was 53 +/- 16 mm Hg (mean +/- SD). Before NSRT, MCE was performed in all patients with intracoronary sonicated albumin (Albunex). Diluted sonicated albumin (Albunex) was selectively injected into the septal perforator arteries during simultaneous transthoracic imaging. Immediately after MCE, ethanol was injected into the same vessel. Plasma total creatine kinase (CK), total CK-MB fraction and CK-MB fraction subforms were measured at baseline and serially for 36 h. RESULTS LVOT gradient decreased to 12 +/- 6 mm Hg (p < 0.001) after NSRT. Accurate mapping of the vascular beds of the septal perforators was successfully attained in all patients by MCE. Furthermore, the MCE risk area correlated well with peak CK (r = 0.79, p < 0.001). Six weeks after NSRT, 23 patients underwent myocardial perfusion studies performed with single-photon emission computed tomography (SPECT). Mean SPECT septal perfusion defect size involved 9.5 +/- 6% of the left ventricle and correlated well with MCE area (r = 0.7), with no statistically significant difference between the risk area estimated by MCE and that by SPECT. CONCLUSIONS Estimation of the size of the septal vascular territory with MCE is accurate, safe and feasible in essentially all patients during NSRT. MCE can delineate the perfusion bed of the septal perforators and can predict the infarct size that follows ethanol injection.

Detection of left anterior descending coronary artery stenosis in patients with left bundle branch block: exercise, adenosine or dobutamine imaging?

OBJECTIVES This study sought to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block. BACKGROUND Patients with left bundle branch block often have septal perfusion defects during exercise perfusion tomography that mimic defects caused by coronary artery disease. These defects appear to be less frequent during pharmacologic stress using adenosine or dipyridamole. Data are scantly on the value of dobutamine tomography in these patients. METHODS We studied 383 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 5-year span. Perfusion tomography was performed in conjunction with exercise in 206 patients, adenosine in 127 and dobutamine in 50. Coronary angiography was performed within 1 month of the nuclear study in 77, 50 and 27 patients, respectively. RESULTS Exercise, adenosine and dobutamine tomography had similar sensitivity and specificity for the detection of > 50% stenosis in the left circumflex (74% and 96%; 50% and 100%; 63% and 91%, respectively) and right coronary arteries (96% and 86%; 82% and 91%; 79% and 100%, respectively) and similar sensitivity for left anterior descending coronary artery stenosis (88%, 79% and 100%, respectively). However, the false-positive rate for septal defects was higher by exercise tomography (26 [46%] of 57) than by pharmacologic methods (5 [10%] of 48, p < 0.001), and there was no significant difference between adenosine (4 [11%] of 35) and dobutamine (1 [8%] of 13, p = 0.7). The specificity and predictive value of a positive test response for left anterior descending coronary artery stenosis were 36% and 51% for exercise compared with 81% and 85% for adenosine (p < or = 0.001) and 80% and 90% for dobutamine (p < 0.05), respectively. CONCLUSIONS In patients with left bundle branch block, pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients.

Relation of the Contractile Reserve of Hibernating Myocardium to Myocardial Structure in Humans

BACKGROUND Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure. METHODS AND RESULTS We evaluated 20 patients with coronary disease (64+/-13 years old, ejection fraction 28+/-7.5%) with DE (up to 40 micrograms . kg(-1). min(-1)), rest-redistribution (201)Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%, P<0.001), higher thallium uptake (69% versus 48%, P=0.03), and less interstitial fibrosis (2% versus 28%, P<0.001). Quantitative angiographic parameters did not predict recovery of function. Segments with DE viability (contractile reserve and/or ischemia) had less fibrosis (2.7% versus 28%, P<0.001), less vimentin and fibronectin (both P<0.01), more glycogen (P=0.016), and higher thallium uptake (64% versus 35.5%, P<0.05) than those without viability. Viable segments by both DE and thallium had less fibrosis (1%) than those viable by 1 of the 2 techniques (9%) or not viable by both (28%, P=0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis (r=-0.83, P<0.01). CONCLUSIONS Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.