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Extent of Left Ventricular Scar Predicts Outcomes in Ischemic Cardiomyopathy Patients With Significantly Reduced Systolic Function

A Delayed Hyperenhancement Cardiac Magnetic Resonance Study

Deborah H. Kwon, MD^_*, Carmel M. Halley, MD^_*, Thomas P. Carrigan, MD, Victoria Zysek, DO, Zoran B. Popovic, MD, PhD^_*, Randolph Setser, PhD, Paul Schoenhagen, MD^_*,, Randall C. Starling, MD, MPH^_*, Scott D. Flamm, MD^_*,, Milind Y. Desai, MD^_*,,_*

^_* Department Cardiovascular Medicine, Cleveland, Ohio
Department of Internal Medicine, Cleveland, Ohio
Department of Radiology, Cleveland Clinic, Cleveland, Ohio

	Abstract

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 
Objectives: The objective of the study was to determine whether the extent of left ventricular scar, measured with delayed hyperenhancement cardiac magnetic resonance (DHE-CMR), predicts survival in patients with ischemic cardiomyopathy (ICM) and severely reduced left ventricular ejection fraction (LVEF).

Background: Patients with ICM and reduced LVEF have poor survival. Such patients have a high myocardial scar burden. CMR is highly accurate in delineation of myocardial scar.

Methods: We studied 349 patients (76% men) with severe ICM (70% disease in 1 epicardial coronary, and mean LVEF of 24%) that underwent DHE-CMR (Siemens 1.5-T scanner, Erlangen, Germany), between 2003 and 2006. Scar (quantified as percentage of myocardium) was defined on DHE-MR images as an intensity >2 standard deviations above the viable myocardium. Transmurality score was semiquantitatively recorded in a 17-segment model as: 0 = no scar, 1 = 1% to 25% scar, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = >75%. The LVEF, demographic data, risk factors, need for cardiac transplantation (CTx), and all-cause mortality were recorded.

Results: The mean age and follow-up were 65 ± 11 years and 2.6 ± 1.2 years (median 2.4 years [1.1, 3.5]), respectively. There were 56 events (51 deaths and 5 CTx). Mean scar percentage and transmurality score were higher in patients with events versus those without (39 ± 22 vs. 30 ± 20, p = 0.003, and 9.7 ± 5 vs. 7.8 ± 5, p = 0.004). On Cox proportional hazard survival analysis, quantified scar was greater than the median (30% of total myocardium), and female gender predicted events (relative risk 1.75 [95% Confidence Interval: 1.02 to 3.03] and relative risk 1.83 [95% Confidence Interval: 1.06 to 3.16], respectively, both p = 0.03).

Conclusions: In patients with ICM and severely reduced LVEF, a greater extent of myocardial scar, delineated by DHE-CMR is associated with increased mortality or the need for cardiac transplantation, potentially aiding further risk-stratification.

Key Words: delayed hyperenhancement CMR and outcomes • ischemic cardiomyopathy

Abbreviations and Acronyms   ACE-I = angiotensin-converting enzyme inhibitor   bSSFP = balanced steady-state free precession   CAD = coronary artery disease   CMR = cardiac magnetic resonance   CTx = cardiac transplantation   DHE-CMR = delayed hyperenhancement cardiac magnetic resonance   ICD = implantable cardioverter defibrillator   ICM = ischemic cardiomyopathy

Delayed hyperenhancement cardiac magnetic resonance (DHE-CMR), after administration of a gadolinium-based contrast agent, has been shown to identify areas of myocardial infarction (MI) with a high degree of accuracy and reproducibility (6–9). Studies have clearly demonstrated the role of DHE-CMR in predicting functional recovery after revascularization in patients with ICM (10,11). Furthermore, recent data also indicate that infarct size, quantified by DHE-CMR, identifies patients at risk for inducible ventricular tachycardia and mortality, more reliably than left ventricular ejection fraction (LVEF) (3,12).

In patients with systolic LV dysfunction due to ICM, LVEF has been shown to be a strong predictor of sudden death (13,14) and might be a surrogate marker for infarct size. However, it is unclear whether the amount of MI-related scar tissue further impacts survival in such patients. We sought to determine whether precise quantification of infarct (scar) size by DHE-CMR is associated with survival in patients with ICM and severe LV systolic dysfunction.

	Methods

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 
This was an observational study of 349 patients with documented ICM (on the basis of 70% stenosis in at least 1 epicardial coronary vessel on angiography and/or history of MI or coronary revascularization), who were referred for the assessment of myocardial viability with cardiac magnetic resonance (CMR) between January 2003 and December 2006. Patients with standard CMR contraindications—including severe claustrophobia, atrial fibrillation, and the presence of pacemakers, defibrillators, or aneurysm clips—were not imaged. Also, no patients were imaged in the immediate peri-infarct period. Electronic medical records were queried to determine clinical and demographic variables, at a time temporally closest to the CMR study (within 1 month). Medication use, including beta-blockers, angiotensin-converting enzyme inhibitors (ACE-I) (angiotensin receptor blockers included in this group), spironolactone, and statins, were recorded. The incidence of post-CMR study coronary revascularization (either percutaneous or surgical) and placement of implantable cardioverter defibrillators (ICD)/cardiac resynchronization therapy (CRT) was also recorded. The institution's angiographic database was queried to assess for presence and degree of CAD. All patients had 70% stenosis in 1 epicardial coronary vessel or had a documented history of MI and/or previous coronary revascularization (corroborating the diagnosis of ICM). The institution's echocardiography database was similarly queried (data from surface echocardiogram performed within 1 week of the CMR study were recorded). All patients had to have an LVEF <45% on initial surface echocardiography, to be considered in the study population. The institution's cardiac transplantation (CTx) database was queried to ascertain any history of such, after the CMR study. All-cause mortality was ascertained by social security death index. We measured a composite end point of all-cause mortality or CTx in the period after CMR study. This study was approved by the institutional review board with a waiver of individual consent.

CMR protocol and analysis.   The CMR examinations were performed on 1.5-T MR scanners (Siemens Medical Solutions, Erlangen, Germany), either Sonata (for examinations between 2002 and 2005, 40 mT/m maximum gradient strength, 200 T/m/s maximum slew rate) or Avanto (for examinations in 2006, 45 mT/m maximum gradient strength, 200 T/m/s maximum slew rate), with electrocardiographic gating. Scout images were acquired initially to identify the cardiac axes. For assessment of global cardiac function, balanced steady-state free precession (bSSFP) images were then acquired: echo time = 1.6 ms, repetition time = 3.3 ms, flip angle = 70°, and slice thickness = 6 mm (long-axis images) or 8 to 10 mm (contiguous short-axis images encompassing the entire LV volume, from apex to base). For short-axis images, the field of view varied from 228 to 330 in the x-direction and 260 to 330 in the y-direction, and matrix size varied from 140 to 180 in the x-direction (phase encoding direction) and 256 in the y-direction. This gave a spatial resolution of 1.5 to 2.1 mm (x-direction) x 1.1 to 1.4 mm (y-direction). In long-axis images, the field of view varied from 250 to 320 (x-direction) and 280 to 340 (y-direction). Matrix size varied from 120 to 210 in the x-direction (phase encoding direction) and 256 in the y-direction. This gave a spatial resolution of 1.5 to 2.1 mm (x-dir) x 1.1 to 1.6 mm (y-direction). For patients able to suspend respiration, breath hold duration was 10 to 15 s, depending on the heart rate; otherwise, images were acquired with 3 signal averages. The LV volumes and LVEF were calculated on the basis of short-axis bSSFP images.

Subsequently, DHE-CMR images were obtained in the same long- and short-axis orientations as the previously described bSSFP images, approximately 20 min after injection of 0.2 mmol/kg of Gadolinium dimenglumine (Magnevist, Berlex Imaging, Wayne, New Jersey), with a phase-sensitive inversion recovery spoiled gradient echo sequence: echocardiography time 4 ms, repetition time 8 ms, flip angle 30°, bandwidth 140 Hz/pixel, 23 k-space lines acquired every other RR-interval, field of view (varied from 228 to 330 in the x-direction and 260 to 330 in the y-direction), and matrix size (varied from 140 to 180 in the x-direction and 256 in the y-direction). This gave a spatial resolution of 1.5 to 2.1 mm (x-direction) by 1.1 to 1.4 mm (y-direction).

For DHE-CMR analysis, the images were first loaded on a custom analysis package (VPT software, Siemens Medical Solutions), and endocardial and epicardial myocardial edges were manually delineated on the DHE-CMR images. Scar was defined as having an intensity >2 standard deviations above viable myocardium (identified by a user-specified region of interest) (Fig. 1) (15,16). Any areas that were identified as scar by the software but not deemed to be scar by the user (e.g., areas outside of the epicardium that were included due to irregular heart borders) were excluded manually by the user. Scar burden was assessed both quantitatively and qualitatively (by investigators D.H.K., C.M.H., and M.Y.D.): 1) quantity of scar was automatically determined (as percentage of total myocardium; such quantitative scar analysis has been shown to be highly reproducible in a previous study from our institution with a bias of only 1% both between and within readers on Bland-Altman analysis and intraclass correlation coefficients of 0.84 and 0.88 for interobserver and intraobserver agreement, respectively [15]; and 2) each study was also semiquantitatively graded, with a standard American Heart Association 17-segment model (17), on a 5-point scale (segmental scar score), with 0 = absence of DHE; 1 = DHE of 1% to 25% of LV segment; 2 = DHE extending to 26% to 50%; 3 = DHE extending to 51% to 75%; and 4 = DHE extending to 76% to 100% (7). To further semiquantitatively define the extent/transmurality of scar tissue, the following definitions were used (18): 1) transmurality score, defined as number of segments with a segmental scar score of 3 or 4; and 2) total scar score, defined as summed segmental scar scores/patient divided by 17 (which reflects the damage/patient, with the maximum possible score being 4). The CMR analysis was completely blinded from the clinical analysis.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Short-Axis Delayed Hyperenhancement Image, Loaded on Custom VPT Software (Siemens Research), for Scar Analysis Each short-axis level was segmented (white lines) according to the standard American Heart Association 17-segment model. The blue circle represents identification of the normal nulled myocardium and adjacent tissues, for the purpose of thresholding (as recommended by the developer of the software). The green and red circles represent delineation of epicardium and endocardium. The bright red areas within the myocardium represent the automatically detected myocardial scar.

	Results

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 
Patient population.   The mean age of the study population (n = 349) was 65 ± 11 years, with the majority being Caucasian (86%) and male (76%). In the study, the mean age for men versus women was similar (66 ± 11 years vs. 64 ± 12 years, p = 0.20). Over a mean follow up of 2.6 ± 1.2 years (median 2.4 years [interquartile range 1.1, 3.5]), there were a total of 56 composite events (51 deaths and 5 CTxs). The patients were subsequently divided into 2 groups: group 1 (no events) and group 2 (composite events). Baseline characteristics of the 2 groups are provided in Table 1. The LVEF was depressed to a similar extent in both groups (75% of the study population had an LVEF <30%) along with a similar frequency of other cardiac risk factors (Table 1). The frequency of post-CMR-revascularization and ICD/CRT was also similar in both groups. In the follow-up period, 30% of patients that underwent revascularization had an improvement in LVEF >35%. In the follow-up period, there was no significant difference in the rate of ICD discharges between the 2 groups (4% vs. 7%, p = 0.26). To ascertain the similarity of baseline characteristics in 2 groups, we also calculated propensity scores.

Subsequently, we compared the scar burden in 2 groups. As shown in Table 2, the mean quantitative scar percentage and semiquantitative scores (transmurality score and total scar score) were significantly higher in those with events versus those without. Kaplan-Meier survival curves on the basis of quartiles of quantitative scar percentage, transmurality score, and total scar score are shown in Figures 2A to 2C. Finally, to account for multiple confounding factors impacting outcomes, we performed univariable and multivariable Cox proportional hazards analysis (Table 3). Receiver-operator characteristic curve analysis testing the association between quantitative scar percentage and events was significant (area under the curve 0.62, p = 0.003). Because of a significant association between quantitative and semiquantitative measures of scar burden, only 1 such measure (quantified scar percentage) was entered into the multivariable model. To account for the potential impact of revascularization (especially within 6 months of CMR) on outcomes, we also performed univariable Cox proportional hazards analysis in a subgroup of patients that did not have revascularization within 6 months of CMR (n = 292, mean age 65 ± 11 years, 219 men, mean LVEF 24 ± 8%). In this subgroup, the relative risk of quantitative scar percentage and total scar score was 1.01 (95% CI: 1.00 to 1.02, p = 0.04) and 1.30 (95% CI: 1.0 to 1.69, p = 0.04), respectively.

View larger version (38K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Kaplan-Meier Curves Demonstrating Difference in Outcomes Among 4 Quartiles (A) Kaplan-Meier curves demonstrating difference in outcomes among 4 quartiles of automatically derived scar (as a percentage of total left ventricular myocardium); 0% to 14% = 1st quartile, 14.1% to 30% = 2nd quartile, 30.1% to 46% = 3rd quartile, and >46% = 4th quartile. (B) Difference in outcomes among 4 quartiles of semiquantitative total scar score; 0 to 1.3 = 1st quartile, 1.31 to 2.3 = 2nd quartile, 2.31 to 3.0 = 3rd quartile, and >3.1 = 4th quartile. (C) Difference in outcomes among 4 quartiles of transmurality score; 0 to 4.0 b 1st quartile, 4.1 to 9.0 b 2nd quartile, 9.1 to 12.0 b 3rd quartile, and >12.0 b 4th quartile.

	Discussion

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

A recent study has also demonstrated the superiority of infarct size, with DHE-CMR, over LVEF and volumes in predicting outcomes in patients after a previous MI (12); however, the mean LVEF (43%) was substantially higher, and the mean LV volumes were substantially smaller, in contrast to the current study. Furthermore, the extent of myocardial scarring (transmurality score as well as total scar score) was substantially lower. The mortality rate was also substantially lower, likely reflecting a lesser-risk population. The current study addresses the incremental value of DHE-CMR in a population that is conceivably at a much higher risk (on the basis of much lower LVEF and higher scar burden), thus extending the spectrum of utility to such high-risk patients.

The characteristics of the current study population were also unique, likely representing the varied referral pattern of our large tertiary care center. The baseline medication data presented in Table 1, which appears suboptimal by modern standards, represents the therapy at the time of initial presentation to our institution. The vast majority of such severely compromised patients get referred to our tertiary care center for high-risk procedures, from outside our primary referral area, as demonstrated in a recent study from our institution (23). This baseline suboptimal therapy likely reflects the reality of medical therapy trends in such patients in nonacademic centers. Indeed, multiple observational studies, from different countries, have demonstrated less-than-optimal medical therapy during follow-up after revascularization procedures (24,25).

In the current population, revascularization in the follow-up period did not provide any survival benefit. Although there could be many potential reasons, a likely reason for the lack of benefit could be that this is already a very high-risk population (because of significantly reduced LVEF and a very high scar burden), and the risks of revascularization potentially outweigh the benefits. However, this is speculative and needs further prospective confirmation. Also, in the current study, there was relatively little difference in the effectiveness of ICD/CRT therapy between the 2 groups. There could be multiple reasons for that, including differences in patient populations between our study and some of the seminal trials of device therapy. Upon comparing our population with that of the MADIT-II (Multicenter Automatic Defibrillator Implantation Trial-II) (26), the mortality rate in the ICD group was similar: 16% over a 27-month follow-up in the MADIT-II versus 14% over 2.6 years' follow-up in our study. However, in the nondevice group for the MADIT-II, the mortality rate was substantially higher compared with our nondevice group (39% vs. 17%). A potential reason, although purely speculative, could be that the MADIT-II, unlike our study, excluded patients that underwent revascularization in close proximity to enrollment. Similar to our study, the MIRACLE (Multicenter InSync Randomized Clinical Evaluation) study of CRT in patients with advanced heart failure (27) only demonstrated a difference in exercise capacity and quality of life, without a difference in overall mortality between patients with and without CRT. In a further analysis of the same study (28), even symptomatic improvements with CRT were less conspicuous in patients with ICM as opposed to nonischemic cardiomyopathy.

Previous studies have demonstrated that both the extent of MI and depressed LVEF are important predictors of survival (3,29,30). Although LVEF is a strong prognostic tool and has been shown to be inversely related to infarct size (31,32), LVEF and volumes are subject to preload, afterload, myopathic processes, and the extent of MI. Therefore, infarct size might be a more objective and superior prognostic indicator. Previous studies, with myocardial perfusion scintigraphy, have demonstrated the incremental prognostic value of infarct sizing over traditional LV volume-based variables (33,34).

DHE-CMR has emerged as an extremely accurate clinical tool in assessment of myocardial viability, with a demonstrated utility in an ischemic setting (9,35). Infarct sizing with DHE-CMR has been shown to correlate with LVEF and other clinical findings in acute infarcts (36) and is highly reproducible (8,37). Due to a higher spatial resolution, DHE-CMR has a greater ability for precise delineation of subendocardial infarctions (38). A recent study demonstrated that clinically unrecognized infarcts, identified by DHE-CMR, were the strongest predictors of major adverse cardiac events and mortality (39). In fact, infarct scar quantified by DHE-CMR was shown to be a better marker of inducible ventricular tachycardia than LVEF (3). DHE-CMR has the ability to not only detect the presence of irreversible myocardial damage but also to delineate transmurality of myocardial scar and the remaining viable myocardium. The transmural extent seen on DHE-CMR has been negatively correlated to the functional outcome after revascularization (10,40).

Clinical implications.   Several trials demonstrated that patients with ICM and systolic dysfunction benefit from various therapies (medications, revascularization, or device therapy) due to restoration of LV size, shape, and ejection fraction (41–43). However, despite such advances, the mortality in such patients remains relatively high, and in some instances (particularly in patients with severe LV dysfunction and severe CAD), the benefits of revascularization might be outweighed by the predicted periprocedural risks. Furthermore, with increasing use of CRT, it is being recognized that more than one-quarter have a progressive worsening of their heart failure despite therapy (44). In recent years, DHE-CMR has been used to help predict potential success for CRT (45–48). In a recent analysis of the MUSTIC (Multi-site Stimulation in Cardiomyopathy) trial, there were suggestions that patients with previous MI fail to respond to CRT, compared with patients with idiopathic dilated cardiomyopathy (49). Furthermore, Bello et al. (50) demonstrated an inverse relationship between absolute scar burden, quantified by DHE-CMR, and functional recovery at 6 months in response to beta-blocker therapy in 45 heart failure patients. In this study, scar burden also predicted recovery of systolic function after revascularization. Therefore, extent of myocardial scarring might be an important determinant of mortality and response to various therapies. It is intuitive to think that risk stratification in patients with congestive heart failure can effectively guide treatment strategies in a cost-effective manner. Our study demonstrates how scar burden is an important prognostic marker and might identify patients at higher risk for death. The STICH (Surgical Treatment for Ischemic Congestive Heart failure) trial is testing whether contemporary medical and device therapy is equivalent to surgical revascularization. A substudy will examine whether viability provides useful risk stratification. However, an important point that needs to be taken into consideration is that, although assessment of myocardial viability and scarring are important, the full picture of myocardium at risk is provided by additional evaluation of ischemia. Hence, future prognostic studies assessing the incremental value of stress-perfusion CMR in combination with DHE-CMR likely need to be conducted.

Study limitations.   Because this is an observational study conducted at a large tertiary referral center, there is a distinct possibility of a selection bias. Only the patients with no contraindications to CMR underwent the examination. In the era of CRT and ICDs, a sizable proportion of patients would have not have qualified for a CMR study, thus leading to selection bias. A likely reason that these patients had not yet received ICD/CRT, despite such reduced LVEF, could be the anticipation that their LVEF would improve after revascularization. Not all patients had ICD/CRT implantation in the post-CMR period, especially because approximately 30% of patients revascularized in the post-CMR period had an improvement in EF >35%. However, there is a possibility that some patients could have had such devices implanted at their local institutions, thus potentially altering their survival. Also, reliance upon the Social Security Death Index for determination of death status might result in an underestimation of clinical outcomes due to the lag time in reporting. The difference in the amount of scar between the 2 groups in our study was modest. This is likely because we are attempting to further risk-stratify patients (on the basis of the amount of scar) that already have severely depressed LVEF, which is in itself is a very powerful prognostic marker. The baseline medication regimen was suboptimal, by today's standards, as discussed in the preceding text. Also, at baseline, there was a difference between groups in use of medical therapy, potentially affecting survival. In some cases, it was likely due to the inability to use some medications due to advanced heart failure. However, this difference should not have made a significant difference in our conclusions, because scar burden was a stronger predictor of death on multivariate survival analysis. Also, the overall propensity scores (generated out of baseline characteristics) were similar in 2 groups. Finally, we did not collect data on diuretic therapy (other than spironolactone) for this study. However, to the best of our knowledge, other than smaller substudies (51), there are no major randomized clinical trials demonstrating mortality association with diuretics.

	Conclusions

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 
In patients with ICM and reduced LV systolic dysfunction, higher LV myocardial scar burden detected on DHE-CMR is associated with significantly worse outcomes, including death or need for CTx, independent of other risk factors, including revascularization or device therapies. Delayed hyperenhancement cardiac magnetic resonance could aid further risk-stratification of this high-risk population.

	Appendix

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 
For a supplementary table, please see the online version of this article.

	Acknowledgments

 
The authors thank Ms. Joan Weaver, RT (CMR), and Ms. Angel Lawrence, RT (CMR), for help with the acquisition of CMR images. They also thank Dr. Thomas O'Donnell (Siemens Research) for providing us with scar analysis software.

	Footnotes

 
The institution receives modest research support from Siemens Medical Solutions.

^_* Reprint requests and correspondence: Dr. Milind Y. Desai, Department of Cardiovascular Medicine, Desk F 15, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 (Email: desaim2{at}ccf.org).

Manuscript received June 9, 2008; revised manuscript received August 29, 2008, accepted September 9, 2008.

	REFERENCES

Top Abstract Methods Results Discussion Conclusions Appendix REFERENCES

 

1. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the International Society for Heart and Lung Transplantation; endorsed by the Heart Failure Society of America J Am Coll Cardiol 2001;38:2101-2113.[Free Full Text]
2. Bax JJ, van der Wall EE, Harbinson M. Radionuclide techniques for the assessment of myocardial viability and hibernation Heart 2004;90(Suppl 5):v26-v33.[Free Full Text]
3. Bello D, Fieno DS, Kim RJ, et al. Infarct morphology identifies patients with substrate for sustained ventricular tachycardia J Am Coll Cardiol 2005;45:1104-1108.[Abstract/Free Full Text]
4. Gheorghiade M, Ruzumna P, Borzak S, Havstad S, Ali A, Goldstein S. Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies Am Heart J 1996;131:250-256.[CrossRef][Web of Science][Medline]
5. Yusuf S, Sleight P, Held P, McMahon S. Routine medical management of acute myocardial infarction. Lessons from overviews of recent randomized controlled trials. Circulation 1990;82:II117-II134.[Medline]
6. Simonetti OP, Kim RJ, Fieno DS, et al. An improved MR imaging technique for the visualization of myocardial infarction Radiology 2001;218:215-223.[Abstract/Free Full Text]
7. Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non–Q-wave myocardial infarction Lancet 2001;357:21-28.[CrossRef][Web of Science][Medline]
8. Mahrholdt H, Wagner A, Holly TA, et al. Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging Circulation 2002;106:2322-2327.[Abstract/Free Full Text]
9. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function Circulation 1999;100:1992-2002.[Abstract/Free Full Text]
10. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction N Engl J Med 2000;343:1445-1453.[Abstract/Free Full Text]
11. Selvanayagam JB, Kardos A, Francis JM, et al. Value of delayed-enhancement cardiovascular magnetic resonance imaging in predicting myocardial viability after surgical revascularization Circulation 2004;110:1535-1541.[Abstract/Free Full Text]
12. Roes SD, Kelle S, Kaandorp TA, et al. Comparison of myocardial infarct size assessed with contrast-enhanced magnetic resonance imaging and left ventricular function and volumes to predict mortality in patients with healed myocardial infarction Am J Cardiol 2007;100:930-936.[CrossRef][Web of Science][Medline]
13. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) Lancet 1999;353:2001-2007.[CrossRef][Web of Science][Medline]
14. Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients Circulation 2005;112:3738-3744.[Abstract/Free Full Text]
15. Setser RM, Bexell DG, O'Donnell TP, et al. Quantitative assessment of myocardial scar in delayed enhancement magnetic resonance imaging J Magn Reson Imaging 2003;18:434-441.[CrossRef][Web of Science][Medline]
16. Kolipaka A, Chatzimavroudis GP, White RD, O'Donnell TP, Setser RM. Segmentation of non-viable myocardium in delayed enhancement magnetic resonance images Int J Cardiovasc Imaging 2005;21:303-311.[CrossRef][Web of Science][Medline]
17. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Int J Cardiovasc Imaging 2002;18:539-542.[Web of Science][Medline]
18. Kaandorp TA, Bax JJ, Lamb HJ, et al. Which parameters on magnetic resonance imaging determine Q waves on the electrocardiogram? Am J Cardiol 2005;95:925-929.[CrossRef][Web of Science][Medline]
19. D'Agostino Jr RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group Stat Med 1998;17:2265-2281.[CrossRef][Web of Science][Medline]
20. Blackstone EH. Comparing apples and oranges J Thorac Cardiovasc Surg 2002;123:8-15.[Free Full Text]
21. Hochman JS, Tamis JE, Thompson TD, et al. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators Sex, clinical presentation, and outcome in patients with acute coronary syndromes N Engl J Med 1999;341:226-232.[Abstract/Free Full Text]
22. Weaver WD, White HD, Wilcox RG, et al. GUSTO-I Investigators Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy JAMA 1996;275:777-782.[Abstract/Free Full Text]
23. Kamdar AR, Meadows TA, Roselli EE, et al. Multidetector computed tomographic angiography in planning of reoperative cardiothoracic surgery Ann Thorac Surg 2008;85:1239-1245.[Abstract/Free Full Text]
24. Yan AT, Yan RT, Tan M, et al. Optimal medical therapy at discharge in patients with acute coronary syndromes: temporal changes, characteristics, and 1-year outcome Am Heart J 2007;154:1108-1115.[CrossRef][Web of Science][Medline]
25. Eagle KA, Kline-Rogers E, Goodman SG, et al. Adherence to evidence-based therapies after discharge for acute coronary syndromes: an ongoing prospective, observational study Am J Med 2004;117:73-81.[CrossRef][Web of Science][Medline]
26. Gomez JF, Zareba W, Moss AJ, McNitt S, Hall WJ. Prognostic value of location and type of myocardial infarction in the setting of advanced left ventricular dysfunction Am J Cardiol 2007;99:642-646.[Medline]
27. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure N Engl J Med 2002;346:1845-1853.[Abstract/Free Full Text]
28. St John Sutton MG, Plappert T, Abraham WT, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure Circulation 2003;107:1985-1990.[Abstract/Free Full Text]
29. Miller TD, Hodge DO, Sutton JM, et al. Usefulness of technetium-99m sestamibi infarct size in predicting posthospital mortality following acute myocardial infarction Am J Cardiol 1998;81:1491-1493.[CrossRef][Web of Science][Medline]
30. Shaw LJ, Hachamovitch R, Berman DS, et al. Economics of Noninvasive Diagnosis (END) Multicenter Study Group The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia J Am Coll Cardiol 1999;33:661-669.[Abstract/Free Full Text]
31. Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ, Gibbons RJ. Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality Circulation 1995;92:334-341.[Abstract/Free Full Text]
32. Zaret BL, Wackers FJ, Terrin ML, et al. The TIMI Study Group Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study J Am Coll Cardiol 1995;26:73-79.[Abstract]
33. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) J Am Coll Cardiol 2004;44:E1-E211.[CrossRef][Medline]
34. Mahmarian JJ, Shaw LJ, Filipchuk NG, et al. A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction J Am Coll Cardiol 2006;48:2448-2457.[Abstract/Free Full Text]
35. Mahrholdt H, Wagner A, Parker M, et al. Relationship of contractile function to transmural extent of infarction in patients with chronic coronary artery disease J Am Coll Cardiol 2003;42:505-512.[Abstract/Free Full Text]
36. Ingkanisorn WP, Rhoads KL, Aletras AH, Kellman P, Arai AE. Gadolinium delayed enhancement cardiovascular magnetic resonance correlates with clinical measures of myocardial infarction J Am Coll Cardiol 2004;43:2253-2259.[Abstract/Free Full Text]
37. Thiele H, Kappl MJ, Conradi S, Niebauer J, Hambrecht R, Schuler G. Reproducibility of chronic and acute infarct size measurement by delayed enhancement-magnetic resonance imaging J Am Coll Cardiol 2006;47:1641-1645.[Abstract/Free Full Text]
38. Wagner A, Mahrholdt H, Holly TA, et al. Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study Lancet 2003;361:374-379.[CrossRef][Web of Science][Medline]
39. Kwong RY, Chan AK, Brown KA, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease Circulation 2006;113:2733-2743.[Abstract/Free Full Text]
40. Choi KM, Kim RJ, Gubernikoff G, Vargas JD, Parker M, Judd RM. Transmural extent of acute myocardial infarction predicts long-term improvement in contractile function Circulation 2001;104:1101-1107.[Abstract/Free Full Text]
41. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 1996;94:2807-2816.[Abstract/Free Full Text]
42. Saxon LA, De Marco T, Schafer J, Chatterjee K, Kumar UN, Foster E. Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling Circulation 2002;105:1304-1310.[Abstract/Free Full Text]
43. Pfeffer MA, Braunwald E, Moye LA, et al. The SAVE Investigators Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669-677.[Abstract]
44. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure N Engl J Med 2005;352:1539-1549.[Abstract/Free Full Text]
45. White JA, Yee R, Yuan X, et al. Delayed enhancement magnetic resonance imaging predicts response to cardiac resynchronization therapy in patients with intraventricular dyssynchrony J Am Coll Cardiol 2006;48:1953-1960.[Abstract/Free Full Text]
46. Bleeker GB, Kaandorp TA, Lamb HJ, et al. Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy Circulation 2006;113:969-976.[Abstract/Free Full Text]
47. Ypenburg C, Roes SD, Bleeker GB, et al. Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy Am J Cardiol 2007;99:657-660.[CrossRef][Web of Science][Medline]
48. Westenberg JJ, Lamb HJ, van der Geest RJ, et al. Assessment of left ventricular dyssynchrony in patients with conduction delay and idiopathic dilated cardiomyopathy: head-to-head comparison between tissue Doppler imaging and velocity-encoded magnetic resonance imaging J Am Coll Cardiol 2006;47:2042-2048.[Abstract/Free Full Text]
49. Duncan A, Wait D, Gibson D, Daubert JC. Left ventricular remodelling and haemodynamic effects of multisite biventricular pacing in patients with left ventricular systolic dysfunction and activation disturbances in sinus rhythm: substudy of the MUSTIC (Multisite Stimulation in Cardiomyopathies) trial Eur Heart J 2003;24:430-441.[Abstract/Free Full Text]
50. Bello D, Shah DJ, Farah GM, et al. Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy Circulation 2003;108:1945-1953.[Abstract/Free Full Text]
51. Hasselblad V, Gattis Stough W, Shah MR, et al. Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial Eur J Heart Fail 2007;9:1064-1069.[Abstract/Free Full Text]

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