Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Image-based models of T-cell distribution identify a clinically meaningful response to a dendritic cell vaccine in patients with glioblastoma.

BACKGROUND: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity. METHODS: Using an image-based modeling approach, we predicted T-cell abundance from serial MRIs of patients enrolled in the dendritic cell (DC) vaccine clinical trial. T-cell predictions were quantified in both the contrast-enhancing and non-enhancing regions of the imageable tumor, and changes over time were assessed. RESULTS: A subset of patients in a DC vaccine clinical trial, who had previously gone undetected, were identified as treatment responsive and benefited from prolonged survival. A mere two months after initial vaccine administration, responsive patients had a decrease in model-predicted T-cells within the contrast-enhancing region, with a simultaneous increase in the T2/FLAIR region. CONCLUSIONS: In a field that has yet to see breakthrough therapies, these results highlight the value of machine learning in enhancing clinical trial assessment, improving our ability to prospectively prognosticate patient outcomes, and advancing the pursuit towards individualized medicine.

Personalized paroxysmal atrial fibrillation ablation by tailoring ablation index to the left atrial wall thickness: the 'Ablate by-LAW' single-centre study-a pilot study.

AIMS: To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation. METHODS AND RESULTS: Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49-66); radiofrequency (RF) time 14 min (12.5-16); and fluoroscopy time 0.7 min (0.5-1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months. CONCLUSION: Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.

Left atrial wall thickness of the pulmonary vein reconnection sites during atrial fibrillation redo procedures.

BACKGROUND: Left atrial wall thickness (LAWT) has been related to pulmonary vein (PV) reconnections after atrial fibrillation (AF) ablation. The aim was to integrate 3D-LAWT maps in the navigation system and analyze the relationship with local reconnection sites during AF-redo procedures. METHODS: Consecutive patients referred for AF-redo ablation were included. Procedure was performed using a single catheter technique. LAWT maps obtained from multidetector computerized tomography (MDCT) were imported into the navigation system. LAWT of the circumferential PV line, the reconnected segment and the reconnected point, were analyzed. RESULTS: Sixty patients [44 (73%) male, age 61 ± 10 years] were included. All reconnected veins were isolated using a single catheter technique with 55 min (IQR 47-67) procedure time and 75 s (IQR 50-120) fluoroscopy time. Mean LAWT of the circumferential PV line was 1.46 ± 0.22 mm. The reconnected segment was thicker than the rest of segments of the circumferential PV line (2.05 + 0.86 vs. 1.47 + 0.76, p < .001 for the LPVs; 1.55 + 0.57 vs. 1.27 + 0.57, p < .001 for the RPVs). Mean reconnection point wall thickness (WT) was at the 82nd percentile of the circumferential line in the LPVs and at the 82nd percentile in the RPVs. CONCLUSION: A single catheter technique is feasible and efficient for AF-redo procedures. Integrating the 3D-LAWT map into the navigation system allows a direct periprocedural estimation of the WT at any point of the LA. Reconnection points were more frequently present in thicker segments of the PV line. The use of 3D-LAWT maps can facilitate reconnection point identification during AF-redo ablation.

Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies.

BACKGROUND: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. METHODS: DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. RESULTS: In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. CONCLUSION: DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients.

BACKGROUND: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. METHODS: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). RESULTS: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test). CONCLUSION: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

Distinct Phenotypic Clusters of Glioblastoma Growth and Response Kinetics Predict Survival.

PURPOSE: Despite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype-growth before treatment and during each treatment to recurrence -has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK. PATIENTS AND METHODS: From our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment. RESULTS: There was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%). CONCLUSION: Dichotomizing the heterogeneity of GBMs into two populations-one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival-suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients.

INTRODUCTION: The usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias. MATERIAL AND METHODS: We analyzed in 63 patients (64 ±14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test. RESULTS: Exercise test (8.1 ±2.7 min, 7.4 ±8.1 metabolic equivalents, 82 ±12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (≥ 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4-66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2-107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3-65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8-65.4)% vs. 27.9 (5.6-64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias. CONCLUSIONS: Plasma BNP values - at baseline or after exercise - were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia.

Acute myocardial infarction: estimation of at-risk and salvaged myocardium at myocardial perfusion SPECT 1 month after infarction.

PURPOSE: To estimate at-risk and salvaged myocardium by using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging after acute myocardial infarction (AMI). MATERIALS AND METHODS: The study was approved by the hospital's Ethical Committee on Clinical Trials (trial register number, PR(HG)36/2000), and all patients gave informed consent. Forty patients (mean age, 61.78 years; eight women) with a first AMI underwent two gated SPECT examinations--one before percutaneous coronary intervention (PCI) and one 4-5 weeks after PCI. Myocardium at risk was estimated by assessing the perfusion defect at the first gated SPECT examination, and salvaged myocardium was estimated by assessing the risk area minus necrosis at the second examination. Myocardium at risk was estimated by determining the discordance between the areas of left ventricular (LV) wall motion and perfusion at the second examination. Concordance between tests was analyzed by means of linear regression analysis, the Pearson correlation, the intraclass correlation coefficient, and Bland-Altman analysis. RESULTS: An improvement in perfusion, wall motion, wall thickening, and LV ejection fraction (P < .001) was observed at 1 month. At 1 month, the area with abnormal wall motion was greater than the area of altered perfusion (35.47 vs 23.1 cm(2); P = .007). The extent of myocardium at risk estimated from this discordance correlated well with myocardium at risk measured at the first gated SPECT examination and with salvaged myocardium between both studies (Pearson correlation: 0.78 and 0.6, respectively). Concordance for correct classification of patients with salvaged myocardium of 50% or greater was 83% (κ = 0.65). CONCLUSION: Myocardial perfusion gated SPECT performed 1 month after early PCI in a first AMI provides potentially useful information on at-risk and salvaged myocardium. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122324/-/DC1.

Usefulness of exercise test and myocardial perfusion-gated single photon emission computed tomography to improve the prediction of major events.

BACKGROUND: The incremental prognostic value of myocardial perfusion-gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated. METHODS AND RESULTS: Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79-0.89; P<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; P=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033). CONCLUSIONS: Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.

Predictive variables for hard cardiac events and coronary revascularization in patients with normal left ventricular myocardial perfusion and systolic function.

BACKGROUND: The objective of this study was to investigate the impact of clinical, electrocardiographic and stress testing variables in predicting hard cardiac events (HE) and coronary revascularization (CR) in patients with normal stress-rest gated SPECT. MATERIALS AND METHODS: Included in the study were 2,004 patients (63.5 ± 12.5 years, 41.6% men) with normal myocardial perfusion and left ventricular ejection fraction (LVEF) >50% on gated SPECT who were followed for HE (cardiovascular death or acute myocardial infarction) and CR. RESULTS: During a follow-up of 4.3 ± 2.4 years, 33 patients (1.6 %; 0.4%/year) had HE and 50 patients (2.5%; 0.6%/year) underwent CR. In a univariate analysis, age ≥65 years, insulin-dependent diabetes mellitus (IDDM), left bundle branch block (LBBB), and pharmacological stress were associated with HE. Independent predictors of HE were age ≥65 years (p < 0.001; HR 6.9), IDDM (p = 0.014; HR 3.4), and LBBB (p = 0.002; HR 4.6). In the univariate analysis, male gender, LVEF, known coronary artery disease (CAD), LBBB, and a positive stress test were associated with CR. Independent predictors of CR were known CAD (p = 0.016; HR 2.1), and a positive stress test (p = 0.006; HR 2.3). CONCLUSION: Age ≥65 years, IDDM, and LBBB are HE-independent predictors in patients with normal myocardial perfusion and normal LVEF on gated SPECT. The presence of known CAD or a positive stress test significantly increases the probability of CR during follow-up.

Gated-SPECT myocardial perfusion imaging as a complementary technique to magnetic resonance imaging in chronic myocardial infarction patients.

INTRODUCTION AND OBJECTIVES: The aim of this study was to compare magnetic resonance and gated-SPECT myocardial perfusion imaging in patients with chronic myocardial infarction. METHODS: Magnetic resonance imaging and gated-SPECT were performed in 104 patients (mean age, 61 [12] years; 87.5% male) with a previous infarction. Left ventricular volumes and ejection fraction and classic late gadolinium enhancement viability criteria (<75% transmurality) were correlated with those of gated-SPECT (uptake >50%) in the 17 segments of the left ventricle. Motion, thickening, and ischemia on SPECT were analyzed in segments showing nonviable tissue or equivocal enhancement features (50%-75% transmurality). RESULTS: A good correlation was observed between the 2 techniques for volumes, ejection fraction (P<.05), and estimated necrotic mass (P<.01). In total, 82 of 264 segments (31%) with >75% enhancement had >50% single SPECT uptake. Of the 106 equivocal segments on magnetic resonance imaging, 68 (64%) had >50% uptake, 41 (38.7%) had normal motion, 46 (43.4%) had normal thickening, and 17 (16%) had ischemic criteria on SPECT. CONCLUSIONS: A third of nonviable segments on magnetic resonance imaging showed >50% uptake on SPECT. Gated-SPECT can be useful in the analysis of motion, thickening, and ischemic criteria in segments with questionable viability on magnetic resonance imaging.

Paradoxical scintigraphic pattern in regions with myocardial necrosis on myocardial perfusion gated SPECT with 99mTc-tetrofosmin.

OBJECTIVES: To assess the significance of a paradoxical pattern (PP) (greater tracer uptake during stress than at rest) on gated myocardial perfusion SPECT in myocardial regions with myocardial necrosis. METHODS: A review of 1,764 consecutive stress-rest myocardial perfusion SPECT studies in patients with prior myocardial infarction (MI) was conducted. Of these, 117 patients (6.6%) with a PP corresponding to a region with myocardial necrosis were identified. An assessment of perfusion, contractility, wall thickening, scintigraphic criteria for viability, and the characteristics of the culprit artery in regions with a PP was performed. RESULTS: Of the 160 regions with necrosis, 125 (75%) had a PP: 67 in the anterior region and 58 in the inferior-lateral region. In the PP group, the average tracer activity of defects during stress was significantly higher than at rest (P < .0001). Ninety-three (86.6%) out of 110 PP segments without scintigraphic criteria of viability at rest met viability criteria on stress imaging. The artery supplying regions with a PP was patent in 88% of cases. In the remaining patients it was occluded, although collateral circulation was always present. CONCLUSIONS: In scintigraphic segments corresponding to regions with infarction and PP, a mixture of viable and well perfused myocardium was observed. In most cases, the vessel that supplied the region with PP was either patent, or when the artery was occluded, there was evident collateral circulation.

Submaximal exercise testing plus atropine in myocardial perfusion SPECT.

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine the diagnostic value of using myocardial perfusion single-photon emission computed tomography (SPECT) with intravenous atropine administration at the end of submaximal exercise testing. METHODS: One milligram of atropine was administered intravenously at the end of exercise testing to 172 patients who underwent a symptom-limited ergometric test but did not reach 80% of their peak heart rate without exhibiting angina or an ST-segment depression ≥1 mm. Within 1 week, 23 patients who satisfied scintigraphic criteria for ischemia during SPECT with atropine underwent SPECT for a second time without atropine administration with the aim of comparing the presence and severity of scintigraphic ischemia between the two studies (SDS: summed difference score). RESULTS: Of the 172 patients, 75 (43.6%) developed angina (n=56) or ST-segment depression (n=30) during atropine administration. Eight of the 23 patients (35%) who underwent two tests exhibited scintigraphic ischemia (SDS ≥2) on only the test with atropine. Furthermore, the SDS was significantly greater on SPECT imaging with atropine (5.6 ± 4.5 vs. 3.1 ± 2.8; P=.0001). CONCLUSIONS: One-third of patients who met scintigraphic criteria for ischemia at the end of submaximal exercise testing and after atropine administration would not have met those criteria without administration of the drug.

Prognostic value of myocardial perfusion-gated SPECT in patients with ischemic cardiomyopathy.

BACKGROUND: There are no extensive series in which risk stratification of patients with ischemic cardiomyopathy (IC) is based on their rest and exercise and scintigraphic characteristics. The purpose of our study was to analyze rest and exercise myocardial perfusion-gated SPECT variables for prognosis in patients with ischemic IC. METHODS AND RESULTS: Prospective cohort study. A study was performed in 167 patients with IC who consecutively underwent rest myocardial perfusion-gated SPECT. In addition, stress SPECT was performed on 137 of these patients. During an average follow-up of 2.3 +/- 1.2 years, cardiac mortality (CM) was 17.4%. Independent predictors of CM in rest-gated SPECT were the positive criteria for myocardial viability (P = 0.027; Hazard risk, HR: 5.1; 95% CI: 1.2-21.4). In the 137 patients who underwent stress-gated SPECT, predictors were scintigraphic criteria for viability plus ischemia (P = 0.026; HR: 3.6; 95% CI: 1.16-11.2) and exercise duration < or = 5 minutes (P = 0.04; HR: 2.7; 95% CI: 1.01-7.36). Coronary angiography variables, performed in 111 patients, did not significantly modify the prognostic value of non-invasive testing. CONCLUSION: Myocardial perfusion-gated SPECT improves prognostic stratification of patients with IC.

Nuclear magnetic resonance-based metabolomics predicts exercise-induced ischemia in patients with suspected coronary artery disease.

The purpose of this study was to develop a (1)H-nuclear magnetic resonance metabolomic approach capable of predicting the occurrence of exercise-induced ischemia in patients with suspected coronary artery disease and to identify the metabolite patterns that contribute most importantly to the prediction. In 31 patients with suspected effort angina and without previous myocardial infarction, serum was obtained just prior to a stress single-photon emission computed tomography. Serum NMR spectra were acquired with pulse-and-acquire and T(2)-edited sequences. The region between 0.50 and 4.25 ppm was used for analysis. Twenty-two patients had reversible myocardial perfusion defects and nine did not. Both groups had similar age and clinical profile, except for more smokers and diabetics in the ischemia group, and attained a similar peak heart rate. The best separation was achieved with long T(2)-edited spectra, 84% of patients being correctly classified based on the partial least square discriminant analysis. The main contributors to discrimination were lactate, glucose, as well as methyl and methylene moieties of lipids and long-chain amino acids. Metabolomic analysis of serum can predict exercise-inducible ischemia in patients with suspected coronary artery disease. This capability could be useful in screening and risk stratification of patients with coronary risk factors.

[Effect of coronary revascularization in patients with ischemic cardiomyopathy who satisfy viability criteria on gated-SPECT assessment of myocardial perfusion]. / Efecto de la revascularización coronaria en la miocardiopatía isquémica con criterios de viabilidad en la gated-SPECT de perfusión miocárdica.

Study on the effects of coronary revascularization and medical treatment on the prognosis of patients with ischemic cardiomyopathy who satisfy myocardial viability criteria on gated single-photon emission computed tomography (SPECT) assessment of myocardial perfusion. In total, 140 consecutive patients with ischemic cardiomyopathy were studied at rest using gated-SPECT and technetium-labeled contrast agents. During a mean follow-up period of 2.3 years after gated-SPECT, the rate of cardiac death in patients who underwent coronary revascularization (n=50) was 16% compared with 26.7% in those who received medical treatment (n=90). Thus, coronary revascularization had a protective effect (hazard ratio = 0.42; 95% confidence interval, 0.17-1.02) in patients with ischemic cardiomyopathy who satisfied myocardial viability criteria.