Citations

Background —Quantitative measures of myocardial perfusion defect severity from acute 99m Tc-sestamibi tomographic images (nadir) have correlated closely with collateral and residual antegrade blood flow during acute myocardial infarction. The purpose of this study was to determine whether a viability threshold could be identified from this measure in patients with acute myocardial infarction treated in a homogeneous manner with successful reperfusion therapy. Methods and Results —The study group consisted of 61 patients with acute myocardial infarction with a risk area of >6% LV treated with primary angioplasty between 120 and 240 minutes after symptom onset. All patients were injected with 20 to 30 mCi of 99m Tc-sestamibi before primary angioplasty and imaged after the procedure. Acute myocardium at risk (MAR) and subsequent infarct size (IS) were quantified by a threshold program. Severity (nadir) from the acute image was the lowest ratio of minimal/maximum counts from 5 short-axis slices. Infarct location was anterior in 22 and inferior in 39 patients. MAR was 33±15% LV and IS was 13±15% LV: 23 patients had no infarction despite MAR similar to those with infarction. Receiver-operator characteristic curve analysis identified a nadir value of 0.26 as providing the best separation of patients with and without infarction (sensitivity, 74%; specificity, 74%). This nadir threshold varied by infarct location: anterior defect, 0.21; inferior defect, 0.31. The sensitivity and specificity for absent infarction for these values were anterior, 69% and 67%, and inferior, 88% and 84%, respectively. Conclusions —In a time frame in which the presence of residual blood flow is important, the severity of the acute 99m Tc-sestamibi defect can be used to predict whether infarction will develop despite successful reperfusion.

Background —The prognostic value of tomographic myocardial perfusion imaging with dipyridamole or adenosine in patients with left bundle-branch block has not been established. Methods and Results —The study group consisted of 245 patients with left bundle-branch block who underwent tomographic (single photon emission tomography) myocardial perfusion imaging with thallium-201 (n=173) or technetium-99m sestamibi (n=72) and either dipyridamole (n=153) or adenosine (n=92) stress. Patients were prospectively classified into two groups. Patients were classified as “high risk” if they had (1) a large severe fixed defect (n=28), (2) a large reversible defect (n=36), or (3) cardiac enlargement and either increased pulmonary uptake (thallium) or a decreased resting ejection fraction (sestamibi) (n=20). The remaining 161 patients (66% of the study group) were at “low risk.” Follow-up was 99% complete at 3±1.4 years. Three-year overall survival was 57% in the high-risk group compared with 87% in the low-risk group ( P <.0001). Survival free of cardiac death/nonfatal myocardial infarction/cardiac transplantation was 55% in the high-risk group and 93% in the low-risk group ( P <.0001). The presence of a high-risk scan had significant incremental prognostic value after adjustment for age, sex, diabetes, and previous myocardial infarction ( P <.0001). Patients with a low-risk scan had an overall survival that was not significantly different from that of a US age-matched population ( P =.86). Conclusions —Tomographic myocardial perfusion imaging with adenosine or dipyridamole stress provides important prognostic information in patients with left bundle-branch block, which is incremental to clinical assessment.

Background Adventitial gene transfer may serve as a tool to study vascular biology and may have therapeutic potential. We investigated the hypothesis that adenovirus-mediated transfer of the gene for endothelial nitric oxide synthase (eNOS) to the adventitia would alter vascular reactivity. Methods and Results Rabbit carotid arteries were surgically isolated and adenoviral vectors encoding eNOS (AdeNOS) or β-galactosidase instilled into the periarterial sheath at a concentration of 1×10 10 pfu/mL. Arteries were harvested 4 days later for immunostaining, NOS enzymatic assay, measurement of cGMP, and vasomotor studies. Transgene expression in the adventitia was confirmed by histochemistry for β-galactosidase and immunostaining for eNOS with a monoclonal antibody. Calcium-dependent NOS enzymatic activity and cGMP levels were significantly greater in the AdeNOS-transduced arteries. Maximal contractions to phenylephrine (10 −5 mol/L) were diminished in the AdeNOS-transduced arteries (4.6±0.2 versus 5.6±0.2 g; P <.05), but in the presence of the eNOS inhibitor N G -monomethyl- l -arginine (3×10 −4 mol/L) there was no difference between the two groups (7.1±0.2 versus 7.5±0.3 g; P =NS). Relaxations to calcium ionophore obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (−log EC 50 , 7.77±0.08 versus 7.45±0.07; P <.02). Conclusions We conclude that eNOS gene transfer to the adventitia alters vascular reactivity, as demonstrated by diminished contractile responses to phenylephrine and enhanced relaxations to calcium ionophore. This may represent a therapeutic strategy for vascular diseases characterized by decreased bioavailability of NO.

Background 99m Tc sestamibi is a recently developed radioisotope that has been used to measure myocardium at risk and infarct size. The relation between these measurements and subsequent patient outcome has not yet been demonstrated. Methods and Results Two hundred seventy-four consecutive patients with acute myocardial infarction underwent tomographic 99m Tc sestamibi imaging on arrival at the hospital (to measure myocardium at risk before reperfusion therapy) and at hospital discharge (to measure the amount of salvaged myocardium and final infarct size). Defect size on the sestamibi images was quantified using a threshold value of 60% of peak counts from the circumferential count profile curves generated for five representative slices of the left ventricle. Patients were followed after hospital discharge to evaluate the association between final infarct size and subsequent mortality. The median defect size measured was 27% of the left ventricle at presentation to the hospital (range, 0% to 77%) and was 12% of the left ventricle at hospital discharge (range, 0% to 68%). Almost one half of the patients had a final infarct size of ≤10%. The median amount of myocardium salvaged was 9% (range, −31% to 75%). During a median duration of follow-up of 12 months, there were 10 deaths (7 cardiac and 3 noncardiac) and 1 resuscitated out-of-hospital cardiac arrest. There was a significant association between infarct size and overall mortality (χ 2 =8.66, P =.003) and cardiac mortality (χ 2 =11.89, P <.001). Two-year mortality was 7% for patients whose infarct size was ≥12% versus 0% for patients whose infarct size was <12%. There also was a significant association between myocardium at risk and cardiac mortality (χ 2 =6.87, P =.009). There was no association between myocardium at risk and overall mortality or between amount of myocardium salvaged and either overall mortality or cardiac mortality. Conclusions Larger infarct size measured by 99m Tc sestamibi imaging after acute myocardial infarction is associated with increased mortality risk during short-term follow-up.

Abstract—Adrenal zona glomerulosa (ZG) cells do not contain nitric oxide (NO) synthase (NOS). We conferred endothelial NOS activity onto adrenal ZG cells through transduction with a recombinant adenovirus encoding the endothelial NOS gene (AdeNOS) to determine the effect of endogenous NO on aldosterone synthesis. A 135-kDa protein band immunoreactive to anti–endothelial NOS antibody was observed in Western blots of AdeNOS-transduced ZG cells but not in control cells or cells transduced with adenovirus encoding the β-galactosidase gene (AdβGal). Nitrate/nitrite production in AdeNOS-transduced ZG cells increased from 0.15±0.01 to 0.27±0.01 μmol/L after stimulation with 1 nmol/L angiotensin II. The treatment of AdeNOS-transduced cells with 30 μmol/Ll-nitro-arginine decreased angiotensin II–stimulated nitrite production from 0.27±0.01 to 0.17±0.01 μmol/L. Basal and angiotensin II–stimulated nitrite production was not increased in AdβGal-transduced or control cells. AdeNOS-transduced cells demonstrated diaminofluorescein-2 diacetate fluorescence, which was blocked by pretreatment withl-nitro-arginine. Angiotensin II–stimulated aldosterone synthesis decreased from 5123±177 pg/mL in AdβGal-transduced ZG cells to 72±27 pg/mL in AdeNOS-transduced cells. Treatment with the NOS inhibitor thiocitrulline (30 μmol/L) increased angiotensin II–stimulated aldosterone synthesis to 2158±45 pg/mL after AdeNOS transduction. These data demonstrate that adenovirus-mediated gene transfer of eNOS in ZG cells results in the expression of active endothelial NOS enzyme and that this endogenous NO production by ZG cells decreases aldosterone synthesis.

The objectives of the present study were to determine whether sodium-lithium countertransport contributes to predicting the probability of having hypertension and to determine whether it does so after other predictor traits have been considered. We used logistic regression to model the relation between sodium-lithium countertransport and the probability of having hypertension, estimated by the prevalence of hypertension among 172 men and 252 women, aged 47-89 years, from the Caucasian population of Rochester, Minn. When sodium-lithium countertransport was the only predictor trait considered, it made a statistically significant contribution to prediction both in men (model chi(2)1df = 20.50, p < 0.001) and in women (model chi(2)1df = 16.69, p < 0.001). For each standard deviation increase in sodium-lithium counter-transport, the expected odds of having hypertension increased 2.25 times in men (95% confidence interval [CI], 1.44-3.51) and 1.77 times in women (95% CI, 1.32-2.37). When sodium-lithium countertransport was not considered, the other traits identified as predictors were age, body mass index, and plasma apolipoprotein CII and CII squared; plasma apolipoprotein AI was an additional predictor in women but not in men. When sodium-lithium countertransport was added to models that included the other predictors, it improved prediction both in men (increase in model chi(2)1df = 12.29, p < 0.001) and in women (increase in model chi(2)1df = 4.86, p < 0.027). Based on these complete models, when the other predictors remained at their mean values, each standard deviation increase in sodium-lithium countertransport increased the expected odds of having hypertension 2.06 times in men (95% CI, 1.31-3.22) and 1.48 times in women (95% CI, 1.04-2.21). These results establish that sodium-lithium countertransport provides information that is helpful in predicting the probability of having hypertension and is not reflected in other identified predictor traits.

BACKGROUND In acute myocardial infarction, residual flow to the infarct zone either through antegrade flow in the infarct-related coronary artery or collateral flow from the non-infarct-related arteries is often present before reperfusion therapy. The purpose of this study was to assess the influence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before successful direct angioplasty on infarct size and myocardial salvage in patients with acute evolving myocardial infarction. METHODS AND RESULTS Sixty patients with acute evolving myocardial infarction underwent direct successful angioplasty without prior thrombolytic therapy. The myocardium at risk of infarction, the final infarct size, and myocardial salvage were measured by tomographic perfusion imaging with 99mTc sestamibi. Antegrade flow in the infarct-related artery before intervention was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study group classification. Collateral flow to the infarct zone before angioplasty was also graded (0 through 3, 0 being no collateral flow). The presence of even minimal antegrade flow before angioplasty (TIMI grade 1) in the infarct-related artery compared with absent flow was associated with a significant reduction in final infarct size (9 +/- 17% versus 23 +/- 19% of left ventricle, P = .02) and a significant increase in myocardial salvage (23 +/- 16% versus 14 +/- 13% of left ventricle, P = .05) after angioplasty. When antegrade flow in the infarct-related artery was absent before angioplasty, the presence of collateral flow before angioplasty resulted in a significantly smaller final infarct size (P = .01) and more myocardial salvage (P = .05) after angioplasty. Both antegrade infarct-related artery flow and collateral flow to the infarct zone had significant independent ability to predict infarct size after angioplasty. When collateral grade and TIMI grade were added to provide an estimate of residual flow, a model including residual flow, myocardium at risk, and the interaction of residual flow and infarct site explained 83% of the variability in infarct size after angioplasty. CONCLUSIONS The presence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before direct angioplasty in acute evolving infarction results in a smaller infarct size after direct successful angioplasty.

BACKGROUND Experimental animal studies have demonstrated that myocardium at risk, residual collateral flow, and duration of coronary artery occlusion are important determinants of final infarct size. The present study examined these variables in patients with acute myocardial infarction in relation to final infarct size. METHODS AND RESULTS Myocardium at risk was assessed with hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc sestamibi) in 89 patients with first-time myocardial infarction (anterior, 48 patients; inferior, 41 patients). All patients had successful reperfusion therapy with either intravenous thrombolysis (32 patients) or primary coronary angioplasty (57 patients) within 24 hours of the onset of chest pain (4.7 +/- 3.9 hours; range, 0.5-21.5 hours) documented by coronary angiography. 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1-6 hours later. Myocardium at risk was quantitated for each patient and expressed as a percentage of the left ventricle: 35 +/- 19%; range, 2-73%. Collateral flow was estimated by both invasive and noninvasive methods. Fifty-three patients with TIMI grade 0 or I flow who underwent primary coronary angioplasty had collateral flow graded angiographically (0-3) before the first balloon inflation. All patients had collateral flow estimated noninvasively from the acute sestamibi short-axis profile curve by three methods that assess the severity of the perfusion defect. Each of these three methods was significantly associated with angiographic collateral grade. Final infarct size was determined at hospital discharge by a second sestamibi study (17 +/- 17%; range, 0-59%). Myocardium at risk (r = 0.61, p less than 0.0001), angiographic collateral grade (p = 0.0003), and radionuclide estimates of collateral flow (r = 0.69-0.70, all p less than 0.0001) were all significantly associated with final infarct size. The time to reperfusion therapy was not significantly associated with final infarct size by univariate analysis (r = 0.18, p = 0.10). Two multivariate models were constructed to determine which variables were independently associated with final infarct size. In the invasive model, myocardium at risk, angiographic collateral grade with an interaction term for infarct location, and time to reperfusion were all independently significant and accounted for 70% of the variability in final infarct size. The noninvasive model, which substituted a radionuclide estimate of collateral flow for angiographic collateral grade, showed nearly identical results, accounting for 68% of the variability in infarct size in patients where the infarct artery was known to be occluded. When all patients were included (patients with and without acute angiography), the noninvasive model accounted for 59% of the variability in infarct size. CONCLUSIONS Myocardium at risk, collateral flow, and duration of coronary occlusion are each independently associated with final infarct size and account for most of its variability. Ideally, all three parameters should be examined in evaluation of the efficacy of new treatment strategies for acute myocardial infarction.

BACKGROUND Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

BACKGROUND Prior studies based on autopsy data suggest that infarction of more than 40% of the left ventricle necessitates cardiogenic shock and death. METHODS AND RESULTS Technetium-99m Sestamibi tomography was used prospectively to measure infarct size at discharge in 166 patients with acute myocardial infarction. Patients with previous myocardial infarction or revascularization were excluded from the trial. Sixteen patients were identified with final infarct sizes > 40% of the left ventricle despite acute reperfusion therapy. These 16 patients (13 men) had a mean age of 63 +/- 10 years; 44% had a previous history of angina. Ten patients had emergent coronary angioplasty only (mean time to percutaneous transluminal coronary angioplasty [PTCA], 6.0 +/- 3.0 hours); 6 had thrombolysis (mean time to tissue plasminogen activator, 4.0 +/- 1.5 hours), of which 2 had rescue PTCA (5 and 3 hours from onset of pain). Of 15 patients who had angiograms after therapy, 15 had open infarct-related arteries. The left anterior descending artery was the infarct-related artery in 14 (9 proximal and 5 distal lesions). Half the patients had only single-vessel disease. Infarct size measured 50 +/- 7% of the left ventricle (range, 42% to 68%). Ejection fraction by radionuclide angiogram was 0.33 +/- 0.09 and 0.38 +/- 0.07 at discharge and 6 weeks, respectively. Hospital complications included shock (1 patient), pulmonary edema (2), angina (3), symptomatic nonsustained ventricular tachycardia (1), transient complete heart block (2), and transient bifascicular block (1). At follow-up (13 +/- 9 months), the patient with shock had died, but the remaining 15 patients were asymptomatic (1 had late PTCA for angina). CONCLUSIONS In the interventional and thrombolytic era, patients with large residual myocardial infarctions can survive without heart failure.