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Cardiovascular disease is a significant cause of morbidity and mortality after renal transplantation. Pretransplant screening in a subset of these patients for occult coronary artery disease (CAD) may improve outcome. The objective of this study was to examine the outcome of 600 patients after renal transplantation for end-stage renal disease. Prospective outcome data were collected on 600 consecutive patients who had renal transplantation between 1996 and 1998 at our institution at 42 +/- 12 months after surgery. Stress single-photon emission computed tomographic (SPECT) myocardial perfusion imaging was performed in 174 patients before surgery, 136 (78%) of whom had diabetes mellitus. There were a total of 59 events: 17 cardiac deaths, 14 nonfatal myocardial infarctions, and 28 noncardiac deaths. There were 12 cardiac events and 11 noncardiac deaths among those who had SPECT myocardial perfusion imaging. In a multivariate analysis that included important risk factors, age (p = 0.03 and 0.003, respectively) and diabetes (p = 0.02 and 0.005, respectively) were the predictors of total events and cardiac events in patients who did not undergo stress SPECT perfusion imaging. In the subgroup who had stress perfusion imaging, an abnormal perfusion SPECT study was the only predictor of cardiac events (p = 0.006). The 42-month cardiac event-free survival rate was 97% in patients with normal SPECT images and 85% in patients with abnormal SPECT images (RR 5.04, 95% confidence interval 1.4 to 17.6, p = 0.006). Thus, there is a 2.8% event rate per year after renal transplantation, and approximately 50% of these events are noncardiac. In high-risk patients (most of whom had diabetes) with preoperative stress perfusion imaging, those with normal images had significantly lower cardiac events than those with abnormal images. These results have important implications in patient screening and postoperative management. [ABSTRACT FROM AUTHOR]

This study compared qualitative assessment of exercise thallium imaging to quantitative assessment in predicting outcome in 713 patients with 78% prevalence of coronary artery disease by coronary angiography; during a mean follow-up of 52 months, there were 106 hard cardiac events (death or nonfatal myocardial infarction). The qualitative method provided important prognostic information; however, unlike the quantitative technique, less patients were assigned to either the low- or high-risk group and proportionally more patients into the intermediate-risk group, which may limit the clinical usefulness of the technique. [ABSTRACT FROM AUTHOR]

The ECG findings during sudden collapse (syncope or sudden death) in severe aortic stenosis (AS) are not well defined. We conducted a comprehensive review of the literature for ECG data during sudden collapse in patients with AS and provided a case report of our own. There were 37 published cases of syncope or sudden death in patients with severe AS which were documented by ECG. Brady- or ventricular arrhythmias were documented in 34 cases (92%). Bradyarrhythmia (n = 24; 71%) was more common at the time of collapse than ventricular tachyarrhythmia (n = 10; 29%). There was slowing of the sinus rate before bradyarrhythmia in the vast majority of patients with bradyarrhythmia but not in those presenting with ventricular tachyarrhythmia (75% vs 0%; p <0.001). ECG evidence of ischemia (ST-segment depression or elevation) was present in most patients with bradyarrhythmia but not in those with ventricular tachyarrhythmia (75% vs 0%; p = 0.011). In conclusion, our findings suggest that left ventricular baroreceptor activation plays a dominant role in the pathophysiology of sudden collapse in patients with severe AS and suggest that ischemia may play a role as well., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD). Little is known about prevalence of silent ischemia in developing nations. We compared prevalence of silent ischemia in DM to a control group by exercise myocardial perfusion imaging (MPI) and electrocardiogram (ECG) in developing nations. The prospective multinational Ischemia Assessment with Exercise imaging in Asymptomatic Diabetes study recruited participants at 12 sites in Asia, Africa, and Latin America. DM participants were age- and gender-matched 2:1 to non-DM individuals with ≥1 CAD risk factor. Subjects underwent exercise tests that were interpreted in core labs in blinded fashion. The study included 392 DM and 205 control participants. Among participants with diagnostic ECGs, a similar proportion of DM and controls had ischemic ECG (15% vs 12%, p = 0.5). A significantly higher proportion of DM group had MPI abnormalities compared with controls (26% vs 14%, p <0.001). In participants with ischemia on MPI, only 17% had ischemic ECG, whereas in those without ischemia on MPI, 10% had ischemic ECG. In a multivariable model, DM was independently associated with abnormal MPI (odds ratio 2.1, 95% confidence interval 1.3-3.5, p = 0.004). Women were less likely to have ischemia by MPI than men (10% vs 30%, p <0.001) and concordance between ECG and MPI was much worse in women. In conclusion, in this large prospective study, asymptomatic DM participants had (1) more ischemia by exercise MPI than ECG, (2) more ischemia by MPI but not ECG than control group, and (3) ischemia by MPI was less in women than men., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) ≤2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 ± 4 vs 11 ± 4, p = 0.009) and lower HRR (22 ± 16 vs 32 ± 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events., (Copyright © 2013. Published by Elsevier Inc.)

Left bundle branch block (LBBB) causes an abnormal pattern of cardiac activation and affects regional myocardial function. Although recognition of LBBB on the surface electrocardiogram is straightforward, dissecting its effect on patient treatment and outcome can be more challenging. The altered pattern of cardiac activation in LBBB causes electrical and mechanical ventricular dyssynchrony, influences ischemia detection on the surface electrocardiogram, and affects stress testing and imaging modalities dependent on wall motion and thickening. Restoration of synchrony by biventricular pacing can improve symptoms and longevity in carefully selected patients. The diagnostic, prognostic, and therapeutic implications of LBBB across this spectrum are discussed in this review., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We previously reported that ranolazine improves exercise myocardial perfusion. Ranolazine ameliorates myocardial ischemia by augmenting myocardial blood flow; likely by a reduction in the extravascular compression of small vessels. We hypothesized that ranolazine could improve left ventricular (LV) dyssynchrony as assessed by phase analysis of gated single photon emission computed tomographic myocardial perfusion imaging. Patients (n = 32) with known or suspected coronary artery disease and reversible perfusion defects on a clinically indicated stress myocardial perfusion imaging were restudied 4 weeks after ranolazine (500 to 1,000 mg orally twice daily) was added to their conventional treatment in an open-label trial (data previously reported). The LV systolic and diastolic dyssynchrony indexes were obtained using automated phase analysis before and after ranolazine. No significant changes were found in the heart rate or blood pressure (at rest or during stress) after treatment. The perfusion pattern improved in 13 of 18 patients who had undergone exercise testing, but in only 3 of 14 patients who had undergone vasodilator stress testing. No significant changes were seen in the LV ejection fraction or volume after treatment. The systolic and diastolic LV dyssynchrony improved after ranolazine therapy; there was a significant decrease in the systolic phase SD (21 ± 17 vs 18 ± 13, p = 0.04), systolic bandwidth (69 ± 60 vs 53 ± 38, p = 0.03), diastolic SD (29 ± 18 vs 24 ± 15, p = 0.047) and diastolic bandwidth (91 ± 61 vs 72 ± 45, p = 0.02). In conclusion, the present study is the first to show improvements in diastolic and systolic LV synchrony with ranolazine as measured by automated phase analysis of gated single photon emission computed tomographic myocardial perfusion imaging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is a risk factor for incident heart failure (HF) in older adults. However, the extent to which this association is independent of other risk factors remains unclear. Of 5,464 community-dwelling adults ≥65 years old in the Cardiovascular Health Study without baseline HF, 862 had DM (fasting plasma glucose levels ≥126 mg/dl or treatment with insulin or oral hypoglycemic agents). Propensity scores for DM were estimated for each of the 5,464 participants and were used to assemble a cohort of 717 pairs of participants with and without DM who were balanced in 65 baseline characteristics. Incident HF occurred in 31% and 26% of matched participants with and without DM, respectively, during >13 years of follow-up (hazard ratio 1.45 for DM vs no DM, 95% confidence interval [CI] 1.14 to 1.86, p = 0.003). Of the 5,464 participants before matching unadjusted and multivariable-adjusted hazard ratios for incident HF associated with DM were 2.22 (95% CI 1.94 to 2.55, p <0.001) and 1.52 (95% CI 1.30 to 1.78, p <0.001), respectively. All-cause mortality occurred in 57% and 47% of matched participants with and without DM, respectively (hazard ratio 1.35, 95% CI 1.13 to 1.61, p = 0.001). Of matched participants DM-associated hazard ratios for incident peripheral arterial disease, incident acute myocardial infarction, and incident stroke were 2.50 (95% CI 1.45 to 4.32, p = 0.001), 1.37 (95% CI 0.97 to 1.93, p = 0.072), and 1.11 (95% CI 0.81 to 1.51, p = 0.527), respectively. In conclusion, the association of DM with incident HF and all-cause mortality in community-dwelling older adults without HF is independent of major baseline cardiovascular risk factors., (Published by Elsevier Inc.)

The effect of heart rate (HR) on left ventricular (LV) mechanical dyssynchrony has not been studied by phase analysis of myocardial perfusion imaging and has yielded conflicting results by echocardiography. We measured indexes of LV dyssynchrony by automated analysis of gated single-photon emission computed tomography in 140 patients with end-stage renal disease (ESRD) and 133 subjects with normal renal function (control group). Patients with abnormal perfusion pattern or QRS duration >120 ms were excluded. HR at time of acquisition of gated images was recorded. LV ejection fraction (EF), volumes, mass, and 2 indexes of dyssynchrony, phase SD and bandwidth, were derived. Almost 50% of patients in each group had an abnormal LVEF (<50%). HR at rest ranged from 48 to 113 beats/min (75 ± 13). Patients with abnormal LVEF had a higher phase SD (30 ± 13° vs 22 ± 11° and 28 ± 16° vs 15 ± 6° for the ESRD and control groups, respectively, p <0.001 each) and higher histographic bandwidth (88 ± 44° vs 62 ± 33° and 80 ± 49° vs 43 ± 14° for the ESRD and control groups, p <0.001 each). Patients with ESRD and normal LVEF had higher SD and bandwidth than the control group (22 ± 11° vs 15 ± 6° and 62 ± 33° vs 43 ± 14°, respectively, p <0.001 each). The control and ESRD groups were divided into tertiles based on HR. The phase SD and bandwidth were similar in the first (slowest HR) and third (highest HR) tertiles in every group (p = NS). There were no significant correlations between phase SD or bandwidth and HR in either group. In conclusion, within the HR range examined in this cross-sectional study, there was no relation between HR at rest and LV dyssynchrony., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The presence and degree of left ventricular (LV) dyssynchrony in patients with end-stage renal disease (ESRD) has not been well studied. We hypothesized that these patients would be more likely to have mechanical dyssynchrony than a control cohort. The indexes of LV mechanical dyssynchrony were measured by automated analysis of gated single photon emission computed tomography myocardial perfusion imaging in 290 patients with ESRD and 109 control patients. Only patients with normal myocardial perfusion imaging findings and a narrow QRS duration were included. The following variables were derived: LV ejection fraction (EF), volume, mass, and 2 indexes of dyssynchrony, the standard deviation and bandwidth. The standard deviation and bandwidth were significantly greater in those with ESRD (23° ± 13° vs 15° ± 6° and 65° ± 40° vs 42° ± 14°, respectively, p <0.001 for each). The LV volumes and LV mass were significantly lower and LVEF significantly greater in the control group than in the patients with ESRD (p <0.001 for each). The subgroup of 217 patients with ESRD and normal LVEF also had a significantly greater standard deviation and bandwidth than did the control group (21° ± 12° and 57° ± 35°, p <0.001 for each). However, their values were lower than those of the 73 patients with ESRD and a LVEF <50% (30° ± 13° and 90° ± 45°, p <0.001 for each). Finally, 25 patients (9%) with ESRD and none of the control group had a standard deviation >43° (p = 0.01). In conclusion, patients with ESRD had significantly more mechanical dyssynchrony than did the control group, even in absence of electrical dyssynchrony and abnormal LV perfusion or function., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Adenosine and regadenoson cause an increase in heart rate (HR) during myocardial perfusion imaging (MPI). It has been shown that patients with diabetes mellitus have a blunted HR response due to cardiac autonomic dysfunction. It is not known whether the HR response is related to hyperglycemia and the metabolic syndrome (MS). HR changes were assessed in 2,000 patients (643 with diabetes mellitus [DM]) in the Adenoscan Versus Regadenoson Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and ADVANCE MPI 2) trials in relation to MS status and blood sugar level on the day of MPI. The HR response was lower in patients with MS (32.43 +/- 0.52% vs 36.15 +/- 0.71%, p <0.001). An increase in the number of features of MS was associated with a stepwise decrease in the HR response (-0.92% per MS criterion, p <0.05), irrespective of the presence of DM. Increasing blood sugar levels resulted in blunting of the HR response even after controlling for DM and MS (0.60 +/- 0.08% per 10 mg/dl, p <0.001). MS was independently related to the HR response on top of DM, renal function, left ventricular function, gender, age, baseline HR, blood pressure, and beta-blocker use. The overall model was highly associated with the HR response (p <0.001) and able to explain 30% of its variation. In conclusion, the HR response to adenosine and regadenoson is blunted in patients with hyperglycemia and in those with MS. These results suggest that factors that precede the development of DM may be associated with cardiac autonomic neuropathy and may help explain the contribution of hyperglycemia and MS to cardiovascular risk., (Copyright 2010 Elsevier Inc. All rights reserved.)

Myocardial infarct (MI) size is a well-established prognostic marker but the association of serum markers with MI size, as measured by myocardial perfusion imaging (MPI), has not been well studied in patients with hypertrophic cardiomyopathy (HC) after alcohol septal ablation (ASA). Creatine kinase (CK), CK-MB, troponin I, and brain natriuretic peptide were measured before and at multiple points after ASA in patients with HC and were correlated with MI size measured by MPI. MPI at rest was performed in 54 patients with HC at a median of 2 days after ASA. CK, CK-MB, and troponin I increased after ASA to peak levels at 12 hours and their cumulative levels (area under the curve) showed significant correlation with size of MI by MPI (r = 0.544, 0.408, and 0.477, p <0.001, 0.003, and 0.001, respectively). The best marker was level of CK at 12 hours (r = 0.609, p <0.0001) after ASA. Brain natriuretic peptide level did not change significantly after ASA (p = 1.0) and only weakly correlated with MI size by MPI (r = 0.130, p = 0.007). In conclusion, CK, CK-MB, and troponin I measured at 12 hours, at peak, and as the area under the curve correlated well with infarct size, but CK level at 12 hours was the best marker. CK continues to be a useful marker of MI size despite the introduction of newer, more specific markers, especially when infarct onset is known with certainty as in patients with HC undergoing ASA., (Copyright 2010 Elsevier Inc. All rights reserved.)

Regadenoson is a selective A(2A) receptor agonist that was recently approved by the Food and Drug Administration for vasodilator stress myocardial perfusion imaging. Because the drug is cleared by renal excretion, its safety in patients with end-stage renal disease (ESRD) needs to be determined. We studied 277 consecutive patients with ESRD who had undergone regadenoson stress gated single photon emission computed tomography myocardial perfusion imaging and compared their side effect profile and safety outcome to those of 134 patients with normal kidney function. The ESRD group included 164 men (59%) and the control group included 73 men (54%; p = NS). The patients with ESRD were younger than the controls (52 +/- 11 years vs 61 +/- 12 years; p <0.001). The myocardial perfusion imaging findings were abnormal in 53 patients (19%) with ESRD and in 24 patients in the control group (18%; p = NS). The left ventricular ejection fraction was 57 +/- 12% in the ESRD group and 64 +/- 12% in the control group (p <0.001). The changes in heart rate and systolic blood pressure (from baseline to peak stress) were 20 +/- 12 beats/min versus 22 +/- 13 beats/min and -11 +/- 24 mm Hg versus -12 +/- 23 mm Hg in the ESRD and control groups, respectively (p = NS for both). Very few patients in either group reported symptoms during the stress test. No medication-related hospitalizations, serious events, or death occurred in either group within 30 days of the study. In conclusion, this is the first study to document the safety of regadenoson in a large number of patients with ESRD. The drug was well tolerated, and the hemodynamic and side effect profiles were similar to those of patients with normal renal function.

This study examined the relation between heart rate (HR) response to adenosine and outcome in patients with end-stage renal disease (ESRD). The usual HR increase during adenosine infusion was caused by direct sympathetic stimulation. It was hypothesized that a blunted HR response, which was probably caused by sympathetic denervation, would be associated with a worse outcome in patients with ESRD. One hundred thirty-nine patients with ESRD being evaluated for renal transplantation who underwent coronary angiography and adenosine gated single-photon emission computed tomographic myocardial perfusion imaging were followed up for all-cause mortality. Percentage of change in HR (%DeltaHR) was calculated as [(peak HR during adenosine infusion - HR at rest)/HR at rest] * 100. A control group of 54 patients (normal renal function and no diabetes) was included for comparison of HR responses. Mean age of patients was 54 +/- 9 years, 30% were women, and 68% had type-2 diabetes mellitus. %DeltaHR was 19.2 +/- 18% in patients with ESRD versus 33 +/- 25% in the control group (p <0.0001). At a mean follow-up of 3.4 +/- 1.5 years, 50 patients (36%) with ESRD died. %DeltaHR was lower in nonsurvivors than survivors (12.6 +/- 14% vs 23 +/- 19%; p = 0.0017). Patients with %DeltaHR less than the median value were more likely to have lower left ventricular ejection fraction and larger end-diastolic volume (p <0.05 for each). In a multivariate logistic regression model, %DeltaHR alone was an independent predictor of all-cause mortality (adjusted odds ratio 5.5, 95% confidence interval 2.3 to 12.9, p = 0.0001). In conclusion, patients with ESRD had a blunted HR response to adenosine, and degree of blunting was strongly associated with all-cause mortality.

A significant proportion of patients with myocardial infarction are missed upon initial presentation to the emergency department. The 12-lead electrocardiogram (ECG) has a low sensitivity for the detection of acute myocardial infarction, especially if the culprit lesion is in the left circumflex artery (LCA). This study was designed to evaluate the benefit of adding 3 posterior chest leads on top of the 12-lead ECG to detect ischemia resulting from LC disease, using a model of temporary balloon occlusion to produce ischemia. We studied 53 consecutive patients who underwent clinically indicated coronary interventions. At the time of coronary angiography, the balloon was inflated to produce complete occlusion of the proximal LCA. We recorded and analyzed the changes noted on the 15-lead ECG, which included 3 posterior leads in addition to the standard 12 leads. In response to acute occlusion of the LCA, the posterior chest leads showed more ST elevation than the other leads, and more patients had ST elevation in the posterior leads than in any other lead. The 15-lead ECG was able to detect>or=0.5 mm (74% vs 38%, p<0.0001) and >or=1 mm (62% vs 34%, p<0.0001) ST elevation in any 2 contiguous leads more frequently than the 12-lead ECG. In conclusion, the 15-lead ECG identified more patients with posterior myocardial wall ischemia because of temporary balloon occlusion of the LC than the 12-lead ECG. This information may enhance the detection of posterior MI in the emergency department and potentially facilitate early institution of reperfusion therapy.

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. This study examined the prognostic power of stress myocardial perfusion imaging (MPI) in 150 patients with ESRD (mean age 53 +/- 9 years; 30% women; 66% with diabetes mellitus) being evaluated for renal transplantation with known coronary anatomy using angiography. Baseline data in addition to perfusion and angiographic parameters were compared between survivors and nonsurvivors. All-cause mortality was defined as the outcome measure. An abnormal MPI result was present in 85% of patients, 30% had left ventricular (LV) ejection fraction (EF) < or =40%, and 40% had multivessel coronary artery disease using angiography. At a mean follow-up of 3.4 +/- 1.5 years, 53 patients died (35%). LVEF < or =40%, LV dilatation (LV end-diastolic volume >90 ml), and diabetes mellitus were associated with higher mortality (all p <0.05). Both total perfusion defect size and mean number of narrowed coronary arteries using angiography were significantly higher in those who died (p <0.05). In a multivariate model, abnormal MPI results (low LVEF or abnormal perfusion) and diabetes alone were independent predictors of death, whereas number of narrowed arteries using coronary angiography was not. Thus, MPI was a strong predictor of all-cause mortality in patients with ESRD. In conclusion, abnormal MPI results independently predicted worse survival and provided more powerful prognostic data than coronary angiography.

Adenosine infusion, as is used in stress single photon-emission computed tomographic (SPECT) imaging, produces an increase in heart rate (HR) and a decrease in blood pressure (BP). The increase in HR is most likely due to direct sympathetic stimulation rather than a reflex to the decrease in BP. In this study, it was hypothesized that the HR response to adenosine is different in patients with versus without diabetes mellitus (DM) in the setting of normal SPECT imaging results. We studied 60 patients with DM (53% women, mean age 62 +/- 10 years) and 60 controls (50% women, mean age 61 +/- 12 years) (p = NS). All patients underwent adenosine SPECT imaging (140 mug/kg/min for 5 minutes) for clinical indications and had normal perfusion and systolic left ventricular function. HR and BP were measured at baseline and during adenosine infusion. HR ratio was defined as peak HR divided by baseline HR and the change as peak HR minus baseline HR. The change in HR (17 +/- 12 vs 22 +/- 14 beats/min, p = 0.034) and the ratio (1.24 +/- 0.20 vs 1.33 +/- 0.25, p = 0.048) were significantly lower in patients with DM compared with those without DM. The baseline and change in mean BP were not significantly different between the 2 groups. In a stepwise regression analysis model, DM was identified as a predictor of the change in HR (p = 0.022). In conclusion, HR response to adenosine infusion is diminished in patients with DM with normal SPECT imaging results. This is likely due to cardiovascular autonomic neuropathy and may carry important prognostic information.

Alcohol septal ablation (ASA) as a treatment for obstructive hypertrophic cardiomyopathy produces septal infarction. There is a concern that such infarcts could be detrimental. Changes in the size of these infarcts by serial perfusion testing have not been studied. We performed resting serial-gated single-photon emission computed tomographic myocardial perfusion imaging in 30 patients (age 51+/-17 years, 57% were women) who had ASA between September 2003 and March 2007 before, 2+/-0.8 days (early), and 8.4+/-6.9 months (late) after ASA. Patients were also followed clinically and with serial 2-dimensional echocardiography. New York Heart Association class decreased from 3.50+/-0.51 before to 1.14+/-0.36 (p<0.0001) 3 months after ASA. The left ventricular (LV) outflow gradient (by Doppler echocardiography) decreased from 63+/-32 mm Hg before to 28+/-23 mm Hg after ASA (p<0.005). None of the patients had perfusion defects at rest before ASA. After ASA, perfusion defect size, involving the basal septum, decreased from 9.4+/-5.8% early to 5.2+/-4.2% of LV myocardium late after ASA (p<0.001). There were no changes in LV size and ejection fraction after ASA. In conclusion, ASA produces small basal ventricular septal infarcts (resting perfusion abnormality) involving<10% of the LV myocardium (including ventricular septum). There is a significant reduction in the perfusion abnormality late after ASA without an increase in LV outflow obstruction or recurrence of symptoms.

Cardiovascular disease is the major cause of mortality in patients with end-stage renal disease (ESRD). This study examined the all-cause mortality in 3,698 patients with ESRD evaluated for kidney transplantation at our institution from 2001 to 2004. Mean age for the cohort was 48+/-12 years, and 42% were women. Stress myocardial perfusion imaging was done in 2,207 patients (60%) and coronary angiography in 260 patients (7%). There were 622 deaths (17%) during a mean follow-up period of 30+/-15 months. The presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (p=0.6) except in patients with 3-vessel disease (p=0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging, with 2.7% mortality increase for each 1% ejection fraction decrease. In conclusion, left ventricular ejection fraction is a strong predictor of survival in patients with ESRD awaiting renal transplantation. Strategies to improve cardiac function or earlier renal transplantation deserve further studies.

Most patients with ST depression during adenosine infusion have reversible perfusion defects by single-photon emission computed tomographic (SPECT) perfusion images. Occasionally ST depression is observed in the setting of normal perfusion images. The outcome of such patients is controversial. We identified 65 patients who underwent gated SPECT perfusion imaging with adenosine as the stress agent. These patients were selected based on the following criteria: none had previous myocardial infarction or coronary revascularization, all were in sinus rhythm, and none had left bundle branch block. The 65 patients had normal SPECT images but ischemic ST response (>or=1 mm ST depression). There were 52 women and 13 men who were 66 +/- 13 years of age. History of diabetes mellitus was present in 16 patients (25%) and hypertension in 48 patients (74%). At a mean follow-up of 24 months, there were no cardiac deaths or myocardial infarctions, and there were 6 coronary revascularization procedures (2 coronary artery bypass graftings and 4 coronary stentings of 1-vessel coronary disease). One patient died of cancer. In conclusion, patients with no previous myocardial infarction or coronary revascularization who have normal SPECT images have a benign outcome despite the presence of ST depression (0% for death or myocardial infarction and 4.6%/year for coronary revascularization). Balanced ischemia could not be a common cause for discordant perfusion and ST response.

This study showed that the mean left ventricular ejection fraction, end-diastolic volume, end-systolic volume, and muscle mass are comparable in patients with type 2 diabetes mellitus to gender-matched patients who do not have diabetes mellitus, but abnormal ejection fraction is more common in men, although not in women, with diabetes mellitus than without. The ejection fraction was higher and the volumes and muscle mass were lower in women than men in the presence or absence of diabetes mellitus.

Single-photon emission computed tomographic imaging is a useful, noninvasive method to detect coronary artery disease (CAD). We tested the hypothesis that artificial neural network modeling could predict CAD extent better than visual interpretation; 109 patients who underwent stress single-photon emission computed tomography and coronary angiography were selected. Twenty patients who had a <5% probability of CAD were also selected for calculation of normalcy rate. A model was trained for each vessel. Stress images were decreased to 25 points by pixel averaging the polar map. The model output was 1 for vessel stenosis >60% and 0 otherwise. Model sensitivities were 92% (55 of 60) for left anterior descending artery versus 62% (37 of 60) for visual interpretation (p = 0.0002), 69% (20 of 29) for left circumflex artery versus 55% for visual interpretation (p = 0.30), and 94% (45 of 48) for right coronary artery versus 78% for visual interpretation (p = 0.024). Model specificities and normalcy rates were 78% and 85% for the left anterior descending artery, 93% and 100% for the left circumflex artery, and 85% and 90% for the right circumflex artery, respectively. Single-vessel CAD was predicted in 27 of 28 patients (96%) by modeling versus 23 of 28 patients (82%) by visual interpretation (p = 0.11). Multivessel CAD was correctly predicted in 30 of 46 patients (65%) by modeling versus 16 of 46 patients (35%) by visual interpretation (p = 0.004). Thus, artificial neural network models can predict CAD from stress single-photon emission computed tomographic images when using separate models for the 3 major epicardial vessels. Because of their high sensitivity and specificity in detecting extensive CAD, these models have great promise as an aid to correctly identify patients at high risk for CAD.

This study examined the changes in brachial artery diameter and flow velocity in response to intravenous adenosine and compared the results to cuff occlusion and single-photon emission computed tomographic (SPECT) images. The change in diameter was less with adenosine than with cuff occlusion. There was no correlation between the presence of abnormal SPECT images and the responses to adenosine or cuff occlusion in either diameter or flow velocity.

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 +/- 6.7 years) with DM (mean duration 8.2 +/- 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 microg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 microg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (<8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.

It is believed that caffeine attenuates the coronary hyperemic response to adenosine by blocking the A2a receptors. We studied the effect of caffeine on adenosine-induced myocardial hyperemia measured by fractional flow reserve after intracoronary adenosine administration. Fractional flow reserve was not affected by intravenous caffeine infusion at a dose that was comparable to oral consumption.

The role of preoperative stress single-photon emission computed tomographic (SPECT) imaging in patients with end-stage liver disease who underwent liver transplantation is not well established. We reviewed medical records of patients who had liver transplantation at our institution between January 1998 and November 2001. During this time, 339 patients (213 men, aged 51 +/- 11 years) underwent liver transplantation. Of these, 87 patients had preoperative stress SPECT imaging. Diabetes mellitus (30% vs 11%), hypertension (26% vs 12%), and coronary artery disease (15% vs 7%) were more prevalent in those with than without SPECT (p <0.01 each). The stress SPECT perfusion images were normal in 78 patients (91%) and the left ventricular ejection fraction was 72 +/- 10%. SPECT images revealed ascites in 66% and splenomegaly in 83% of patients. There were 35 total deaths (10%) and 5 nonfatal myocardial infarctions over a mean follow-up of 21 +/- 13 months. Most deaths (32 of 35) were noncardiac and sepsis was the most common cause of death. A normal SPECT study had a 99% negative predictive value for perioperative cardiac events. Kaplan-Meier survival curves showed an 87% 2-year cumulative survival rate in the total group. Thus, in patients undergoing liver transplantation, 2-year survival depends on early noncardiac events. A normal stress SPECT study identified patients at a very low risk for early and late cardiac events despite a higher risk profile. SPECT images also revealed unique findings, such as ascites and splenomegaly, which could produce image artifacts and may interfere with accurate image interpretation.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.

Both dobutamine stress echocardiography (DSE) and myocardial perfusion scintigraphy are used to assess myocardial viability. Few studies have compared the data on myocardial viability and ischemia by low and peak dose DSE and myocardial perfusion imaging in the same patients. Fifty-four patients (45 men and 9 women aged 65 +/- 9 years) with ischemic cardiomyopathy (mean ejection fraction 24 +/- 9%) underwent rest 4-hour redistribution thallium-201 single-photon emission computed tomography (SPECT), low and peak dose DSE, and dobutamine sestamibi SPECT. A total of 864 segments were analyzed (16 segments/patient). Wall motion abnormality was present in 796 segments (92%), and contractile reserve during dobutamine infusion was seen in 400 of these segments (50%). Contractile reserve was seen in 331 of 509 hypokinetic segments (65%) and 69 of 287 akinetic/dyskinetic segments (24%) (p <0.001). Contractile reserve was more frequent in segments with normal thallium uptake (64%), reversible thallium defects (42%), or mild to moderate fixed thallium defects (48%) than severely fixed defects (22%) (p <0.05 each). Concordant information about viability by thallium imaging and DSE was obtained in 62% of segments. Dobutamine sestamibi ischemia was seen in 518 of 796 segments (65%) compared with 265 segments (33%) by DSE (p <0.001). Scintigraphic ischemia was noted in 126 of 195 segments (65%) demonstrating biphasic response, 129 of 205 segments (63%) showing sustained improvement, 42 of 70 segments (60%) deteriorating during dobutamine infusion, and 221 of 326 (68%) demonstrating no change (p = NS). Thus, in patients with ischemic cardiomyopathy, contractile reserve is more frequent in hypokinetic segments than akinetic/dyskinetic segments. The number of segments with normal or near-normal thallium uptake or with scintigraphic ischemia is significantly greater than the number of those capable of increasing contractile function or demonstrating an ischemic response during dobutamine echocardiography.

This study shows that in patients with intermediate pretest probability of coronary artery disease stress single-photon emission computed tomography perfusion imaging decreases the rate of coronary angiography and coronary revascularization and is economically a superior strategy to routine coronary angiography.

Myocardial viability assessment is useful in patients with severe coronary artery disease and severe left ventricular dysfunction. Whereas most studies have focused on recovery of regional function, there are emerging data on patient outcome. Review of these data suggests that patients with chronic ischemia, cardiomyopathy, and viable myocardium who are treated medically have a worse, outcome than those treated with coronary revascularization. However, there are no prospective randomized trials. We present perspectives for future studies.

This study examined the prognostic value of single-photon emission computed tomography in angiographically high-risk patients with left main and/or 3-vessel coronary artery disease who were treated medically. Multivariable Cox survival analysis revealed the single-photon emission computed tomography score (based on size of perfusion abnormality, multivessel abnormality, left ventricular dilation, and lung uptake) as the only independent predictor of outcome.

This study showed that quantitative analysis of SPECT perfusion images provide comparable prognostic information to summed stress score in medically treated patients with coronary artery disease.

This study examined the hemodynamic effects of arbutamine, a synthetic catecholamine, in 12 patients with and 7 patients without coronary artery disease. Arbutamine produced a balanced positive inotropic (increase in left ventricular dp/dt) and chronotropic effect (increase in heart rate).

This study examined the predictors of early coronary revascularization in 816 patients with chest pain syndromes who had coronary artery disease by angiography and exercise single-photon emission computed tomography (SPECT) thallium imaging. Multivariate analysis of clinical, stress, nuclear, and catheterization variables revealed the presence of SPECT reversibility as the most powerful predictor (chi-square = 43) of early revascularization.

Previous studies have examined the predictors of outcome in medically treated patients with coronary artery disease (CAD). There is limited information on predictors of outcome after coronary artery bypass grafting (CABG). This study examined the predictors of outcome of 255 patients with CAD, at a mean time of 5 years after CABG for angina pectoris. The 255 patients underwent coronary angiography and stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging after CABG. During a mean follow-up of 41 +/- 28 months after stress testing, there were 34 hard events (24 cardiac deaths and 10 nonfatal myocardial infarctions). The hemodynamics during stress testing, and age and gender were not predictors of events. The SPECT variables of multivessel perfusion abnormality, perfusion deficit size, and increased lung thallium uptake were predictors of death and total events by uni- and multivariate survival analysis. There were 14 events in 45 patients (31%) with multivessel abnormality and increased lung thallium uptake, 14 events in 101 patients (14%) with either multivessel abnormality or increased lung uptake, and 6 events in 109 patients (6%) with neither of these 2 variables (p = 0.0001). The annual mortality and total event rates were 7.5% and 9.5% with both variables, 3.4% and 4.3% with either variable, and 0.6% and 1.7% with neither of the variables (p = 0.01). Thus, stress SPECT perfusion imaging is useful to stratify patients after CABG into low, intermediate, and high risk groups for future cardiac events.

This study examines the prognostic value of simultaneous perfusion and function assessment in 412 patients. The exercise perfusion pattern was a stronger predictor of events (mostly acute nonfatal myocardial infarcts) than resting ejection fraction.