Differentiation of ischemic from nonischemic cardiomyopathy with positron emission tomography

This study was undertaken to determine whether positron emission tomography (PET) performed after the intravenous injection of 11C-palmitate permits differentiation of patients with ischemic from those with nonischemic dilated cardiomyopathy. PET was performed after intravenous injection of 11C-palmitate in 10 patients with ischemic and in 10 with nonischemic dilated cardiomyopathy. Regions of homogeneously severely depressed accumulation of 11C-palmitate, representing 15% or more of the expected myocardial cross-sectional area, were observed in 8 of 10 patients with ischemic but in none of 10 patients with nonischemic cardiomyopathy. Patients with nonischemic cardiomyopathy had marked spatial heterogeneity of the accumulation of palmitate throughout the left ventricular myocardium, whereas most tomographic sections from patients with ischemic cardiomyopathy accumulated 11C-palmitate more homogeneously in regions exclusive of discrete defects indicative of remote infarction. Thus, a larger number of discrete noncontiguous regions (17 +/- 5 compared with 12 +/- 4, p less than 0.001) and greater reduction of average 11C-palmitate content (59 +/- 6 compared with 64 +/- 10% maximal myocardial radioactivity, p less than 0.05) were seen in the tomographic reconstructions from patients with nonischemic than in those from patients with ischemic cardiomyopathy. These findings support the hypothesis that multiple myocardial infarctions underlie the process seen as dilated cardiomyopathy in patients with coronary artery disease. Our findings indicate that PET permits differentiation of patients with ischemic from those with nonischemic cardiomyopathy.     

Distinguishing ischemic cardiomyopathy from nonischemic dilated cardiomyopathy with coronary echocardiography.

Transthoracic echocardiographic examination of the proximal left coronary system was performed in 59 patients who had dilated cardiomyopathy to determine if this technique could distinguish between ischemic and nonischemic dilated cardiomyopathy. With use of annular array transducers (3.5 or 5 MHz) and digital image processing, echocardiographic visualization of the coronary arteries was successful in 55 (93%) of 59 patients. As assessed by coronary angiography, 32 subjects had ischemic cardiomyopathy and 27 had nonischemic cardiomyopathy. Twenty-seven (84%) of the 32 patients who had coronary artery disease and 24 (89%) of the 27 patients with nonischemic cardiomyopathy were correctly identified. The accuracy of coronary echocardiography was 86% in the entire study group and 93% when patients with inadequate studies were excluded. All subjects who had ischemic cardiomyopathy had evidence of disease by coronary echocardiography or segmental wall motion abnormalities. Multivariate analysis permitted correct classification of 93% of all subjects based on the results of the coronary echocardiogram, evaluation of segmental wall motion and a history of prior myocardial infarction. The correct diagnosis was made in 86% when the results of coronary echocardiography were excluded from analysis using all other echocardiographic and clinical variables. Transthoracic coronary echocardiography can be performed with a high degree of success in patients with dilated ventricles and the technique can reliably distinguish between ischemic and nonischemic dilated cardiomyopathy.     

Detection of coronary artery disease with positron emission tomography and rubidium 82.

Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.     

Progression of coronary artery disease in non-ischemic dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is traditionally divided into ischemic and non-ischemic etiologies. We review data from clinical trials that suggest some patients in the latter subgroup develop ischemic complications including fatal myocardial infarction. However, the reasons for and magnitude of the effect are not known. Prospective screening studies and improved endpoint adjudication in clinical trials may be required to better delineate the degree to which the phenomenon occurs. Risk factor modification strategies should be applied to the non-ischemic DCM cohort, especially with continued improvements in survival rates in patients with heart failure.     

Positron emission tomography in coronary artery disease

PURPOSE OF REVIEW: Mortality and coronary events are dramatically reduced in coronary artery disease by intense lifestyle and pharmacologic management without further improvement by revascularization procedures, thereby requiring definitive noninvasive diagnostic imaging. Consequently, this review summarizes the evidence supporting cardiac positron emission tomography as a definitive, noninvasive, 'one-stop' test for routine management of coronary artery disease that is well validated in the scientific literature and illustrated by clinical cases. RECENT FINDINGS: Substantial evidence documents accuracy of positron emission tomography for identifying early or advanced coronary artery disease, quantifying its severity, risk stratification, deciding on revascularization procedures, following progression or regression and for evaluating coronary endothelial function as the basis for preventive treatment. Recent technology like positron emission tomography-computed tomography, however, requires advanced knowledge, training and attention to technical details to avoid common artifactual results and to provide definitive conclusions illustrated in this review. SUMMARY: Cardiac positron emission tomography, done correctly with attention to technical details, provides definitive noninvasive assessment of early or advanced coronary atherosclerosis as the basis for invasive procedures or for lifelong intense risk factor management, demonstrates progression or regression of disease, predicts clinical outcomes and serves as the primary definitive noninvasive guide for managing coronary artery disease.     

Systemic inflammation in nonischemic dilated cardiomyopathy

We investigated links between inflammatory systemic activation and clinical presentation of nonischemic dilated cardiomyopathy (NIDC). Thirty-one consecutive patients with NIDC (age 57 ± 10 years, left ventricular ejection fraction 32% ± 7%) were enrolled in the study: subjects with ischemic heart disease, valvular heart disease, congenital malformations, pulmonary, renal, inflammatory, or metabolic diseases were excluded. All patients underwent physical examination, electrocardiography, chest radiology, echocardiography, and coronary angiography. Plasma levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fibrinogen were ascertained. New York Heart Association (NYHA) functional class was significantly correlated with concentrations of fibrinogen (r = 0.42, P < 0.05) and CRP (r = 0.52, P < 0.01), and with ESR (r = 0.46, P < 0.05). Left ventricular ejection fraction was inversely related to fibrinogen (r = −0.41, P < 0.05) and ln CRP (r = −0.46, P < 0.05). Correlations between NYHA class and markers of inflammation remained significant also after correction for age, sex, and cardiovascular risk factors. Ongoing treatment with statins was associated with reduced CRP levels. Inflammatory markers are increased in patients with NIDC proportionally with severity of symptoms and systolic impairment. Systemic inflammation might be related to deterioration of NYHA class.     

Left atrial deformation and nonischemic dilated cardiomyopathy

Background

Left ventricular filling pressure (LVFP) is raised by the compromised contraction and impaired ventricular compliance in dilated hearts with systolic dysfunction. Timely recognition and staging of this condition are important for planning of the treatment strategy and making the prognosis. Two-dimensional speckle- tracking echocardiography (2D-STE) has recently enabled the quantification of left atrial (LA) myocardial deformation dynamics. In this study, echocardiographic indicators of increased LVFP and NT-pro-BNP were compared with LA strain measured by 2D-STE.

Methods

A total of 49 nonischemic dilated cardiomyopathy (DCMP) patients were included in the study. All patients underwent standard 2D echocardiography. In the 2D-STE analysis of the LA, global longitudinal LA strain during ventricular systole (GLAs-res) and strain during late diastole (GLAs-pump) were obtained. NT-pro-BNP levels were measured. The patients were divided into two groups—normal (group 1) and increased (group 2) LVFP—according to E/A ratio, E velocity, and E/E’ ratio.

Results

LAVi-max, LAVi-min, and NT-pro-BNP were higher in group 2, whereas LAtotalEF, LAactiveEF, GLAs-res, and GLAs-pump were lower. In univariate analysis, a good negative correlation was seen between GLAs-res vs. NT-pro-BNP, GLAs-res vs. LAVi-max, and GLAs-res vs. E/E’ ratio; a good negative correlation was present between GLAs-pump vs. NT-pro-BNP, GLAs-pump vs. LAVi-max, and GLAs-pump vs. E/E’ ratio. LAVi-max, LAactiveEF, NT-pro-BNP, GLas-res, and GLAs-pump were studied by logistic regression analysis. GLAs-res (p?=?0.009, OR?=?0.593, 95?% CI 0.4–0.877), NT-pro-BNP (p?=?0.028, OR?=?1.027, 95?% CI 1.003–1.052), and LAactiveEF (p?=?0.022, OR?=?0.001, 95?% CI 0.001–0.024) were found to be independent predictors of increased LVFP.

Conclusion

2D-STE-based LA function is impaired in patients with nonischemic DCMP. LA reservoir and pump function parameters together with NT-pro-BNP levels might be useful in estimating LVFP in this patient group.     

Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography.

OBJECTIVE. The aim of this study was to determine the prognostic significance of perfusion-metabolism imaging in patients undergoing positron emission tomography for myocardial viability assessment. BACKGROUND. Positron emission tomography using nitrogen-13 ammonia and 18fluorodeoxyglucose to assess myocardial blood flow and metabolism has been shown to predict improvement in wall motion after coronary artery revascularization. The prognostic implications of metabolic imaging in patients with advanced coronary artery disease have not been investigated. METHODS. Eighty-two patients with advanced coronary artery disease and impaired left ventricular function underwent positron emission tomographic imaging between August 1988 and March 1990 to assess myocardial viability before coronary artery revascularization. RESULTS. Forty patients underwent successful revascularization. Patients who exhibited evidence of metabolically compromised myocardium by positron emission tomography (decreased blood flow with preserved metabolism) who did not undergo subsequent revascularization were more likely to experience a myocardial infarction, death, cardiac arrest or late revascularization due to development of new symptoms than were the other patient groups (p less than 0.01). Concordantly decreased flow and metabolism in segments of previous infarction did not affect outcome in patients with or without subsequent revascularization. Those with a compromised myocardium who did undergo revascularization were more likely to experience an improvement in functional class than were patients with preoperative positron emission tomographic findings of concordant decrease in flow and metabolism. CONCLUSIONS. Positron emission tomographic myocardial viability imaging appears to identify patients at increased risk of having an adverse cardiac event or death. Patients with impaired left ventricular function and positron emission tomographic evidence for jeopardized myocardium appear to have the most benefit from a revascularization procedure.     

Regional heterogeneity of function in nonischemic dilated cardiomyopathy

OBJECTIVE: To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS: MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS: DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS: A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.     

Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease

The diagnostic performance of rubidium-82 (Rb-82) positron emission tomography (PET) and thallium-201 (TI-201) single-photon emission-computed tomography (SPECT) for detecting coronary artery disease was investigated in 81 patients (52 men, 29 women). PET studies using 60 mCi of Rb-82 were performed at baseline and after intravenous infusion of 0.56 mg/kg dipyridamole in conjunction with handgrip stress. TI-201 SPECT was performed after dipyridamole-handgrip stress and, in a subset of patients, after treadmill exercise. Sensitivity, specificity and overall diagnostic accuracy were assessed using both visually and quantitatively interpreted coronary angiograms. The overall sensitivity, specificity and accuracy of PET for detection of coronary artery disease (>50% diameter stenosis) were 84,88 and 85%, respectively. In comparison, the performance of SPECT revealed a sensitivity of 84%, specificity of 53% (p < 0.05 vs PET) and accuracy of 79%. Similar results were obtained using either visual or quantitative angiographic criteria for severity of coronary artery disease. In 43 patients without prior myocardial infarction, the sensitivity for detection of disease was 71 and 73%, respectively, similar for both PET and SPECT. There was no significant difference in diagnostic performance between imaging modalities when 2 different modes of stress (exercise treadmill vs intravenous dipyridamole plus handgrip) were used with SPECT imaging. Thus, Rb-82 PET provides improved specificity compared with TI-201 SPECT for identifying coronary artery disease, most likely due to the higher photon energy of Rb-82 and attenuation correction provided by PET. However, post-test referral cannot be entirely excluded as a potential explanation for the lower specificity of TI-201 SPECT.     

Assessment of coronary artery disease severity by positron emission tomography. Comparison with quantitative arteriography in 193 patients

To assess the accuracy of positron emission tomography (PET) for evaluation of coronary artery disease (CAD), cardiac PET perfusion images were obtained at rest and with dipyridamole-handgrip stress in 193 patients undergoing coronary arteriography. PET images were reviewed by two independent readers blinded to clinical data. Subjective defect severity scores were assigned to each myocardial region on a 0 (normal) to 5 (severe) scale. Results were compared with arteriographic stenosis severity expressed as stenosis flow reserve (SFR), with continuous values ranging from 0 (total occlusion) to 5 (normal), calculated from quantitative arteriographic dimensions using automated detection of the vessel borders. There were 115 patients with significant CAD (SFR less than 3), 37 patients with mild CAD (3 less than or equal to SFR less than 4), and 41 patients with essentially normal coronaries (SFR greater than or equal to 4). With increasingly severe impairment of stenosis flow reserve, subjective PET defect severity increased. Despite wide scatter, a PET score of 2 or more was highly predictive of significant flow reserve impairment (SFR less than 3). For each patient, the score of the most severe PET defect correlated with the SFR of that patient's most severe stenosis (rs = 0.77 +/- 0.06). For each of 243 stenoses, PET defect score correlated with the SFR of the corresponding artery (rs = 0.63 +/- 0.08). PET defect location closely matched the region supplied by the diseased artery, and readers agreed whether the most severe PET defect was less than or more than 2 for 89% of patients.     

Clinical variables predicting inappropriate use of implantable cardioverter-defibrillator in patients with coronary heart disease or nonischemic dilated cardiomyopathy

Inappropriate therapy is a common clinical problem in recipients of implantable cardioverter-defibrillators (ICDs). The present study evaluated whether clinical characteristics could predict inappropriate ICD therapy due to atrial tachyarrhythmias in a series of 260 patients.     

Prediction of reversible ischemia after coronary artery bypass grafting by positron emission tomography.

Metabolic imaging using positron emission tomography (PET) facilitates the identification of ischemic but viable myocardium. In this study, the predictive value of PET for identifying improvement in regional function after coronary artery bypass grafting (CABG) was assessed. PET perfusion and metabolic imagings using N-13 ammonia and F-18 deoxyglucose (FDG) were performed before and 5-7 weeks after CABG in 25 patients with coronary artery disease. Each of the 5 myocardial segments of the left ventricle was categorized as normal, ischemic and infarcted based on the findings of perfusion and PET metabolic images. Among 58 hypoperfused segments, abnormal perfusion in 17 of 25 ischemic segments was correctly predicted to be reversible (68% prediction accuracy), and that in 25 of 33 infarcted segments were correctly predicted to be irreversible (76% prediction accuracy) (p < 0.001). Similarly, among 53 asynergy segments assessed by radionuclide ventriculography, abnormal wall motion in 21 of 27 asynergy segments was correctly predicted to be reversible (78% prediction accuracy), and that in 21 of 26 PET viable segments was correctly predicted to be irreversible (81% prediction accuracy) (p < 0.001). Thus, preoperative metabolic imaging using PET appears to be useful for predicting responses to CABG.     

Utility of positron emission tomography in predicting improved left ventricular ejection fraction after coronary artery bypass grafting among patients with ischemic cardiomyopathy

The objective of this study was to determine whether preoperative estimates of regional myocardial uptake of (18)-F-fluorodeoxyglucose (FDG) could predict postoperative improvement in ejection fraction in patients undergoing coronary artery bypass grafting (CABG) for ischemic cardiomyopathy. 20 consecutive patients [left ventricular ejection fraction (LVEF) /=5% change noted in 7 patients (group 1) and <5% noted in 10 patients (group 2). No preoperative or perioperative clinical variable could predict those with improved ventricular function. The relative amount of FDG uptake in the anterior wall was higher in group 1 compared with group 2 (93 +/- 9 vs. 81 +/- 13%; p < 0.05) and correlated with the change in LVEF post-CABG (r = 0.50; p < 0.05). >88% of FDG uptake in the LAD region had a positive predictive accuracy of 67% and negative predictive accuracy of 88% for improved LVEF postbypass. Late follow-up estimates of LVEF (median of 10 months) showed that early changes in function were sustained. In summary, among patients with severe coronary artery disease and depressed LVEF, ventricular function may improve early postrevascularization. PET estimates of relative FDG uptake in the anterior wall help predict those individuals who are likely to have the greatest increment in LVEF.