Complementary Prognostic Values of Stress Myocardial Perfusion and Late Gadolinium Enhancement Imaging by Cardiac Magnetic Resonance in Patients With Known or Suspected Coronary Artery Disease
Background— Recent studies have demonstrated the significant prognostic value of stress cardiac magnetic resonance (CMR) myocardial perfusion imaging. Apart from characterizing reversible perfusion defect (RevPD) from flow-limiting coronary stenosis, CMR late gadolinium enhancement (LGE) imaging is currently the most sensitive method for detecting subendocardial infarction (MI). We therefore tested the hypothesis that characterization of these 2 processes from coronary artery disease by CMR can provide complementary prognostic values.
Methods and Results— We performed CMR myocardial perfusion imaging followed by LGE imaging on 254 patients referred with symptoms of myocardial ischemia. At a median follow-up of 17 months, 49 cardiac events occurred, including 12 cardiac deaths, 16 acute MIs, and 21 cardiac hospitalizations. RevPD and LGE both maintained a >3-fold association with cardiac death or acute MI (death/MI) when adjusted for each other and for the effects of patient age and gender (adjusted hazard ratio, 3.31; P=0.02; and hazard ratio, 3.43; P=0.01, respectively). In patients without a history of MI who had negative RevPD, LGE presence was associated with a >11-fold hazards increase in death/MI. Patients with neither RevPD nor LGE had a 98.1% negative annual event rate for death/MI. For association with major adverse cardiac events, RevPD was the strongest multivariable variable in the best overall model (hazard ratio, 10.92; P<0.0001).
Conclusions— CMR imaging provides robust risk stratification for patients who present with symptoms of ischemia. Characterization of RevPD and LGE by CMR provides strong and complementary prognostic implication for cardiac death or acute MI.
Received August 7, 2008; accepted July 15, 2009.
Recent data have demonstrated that cardiac magnetic resonance (CMR) myocardial perfusion imaging (CMRMPI) provides strong prognosis for cardiac events in patients suspected to have myocardial ischemia. In a study of 513 patients with symptoms of suspected ischemia, Jahnke et al1 reported strong prognostic association of CMRMPI results with cardiac death or nonfatal myocardial infarction (MI). Apart from characterizing reversible perfusion defect (RevPD) reflecting hemodynamically significant coronary artery disease (CAD), late gadolinium enhancement (LGE) imaging offers the most sensitive method for detecting subendocardial MI. It is unclear whether combining CMRMPI and LGE imaging provides complementary diagnostic and prognostic value important to patient care. In this study, we hypothesize that because CMRMPI and LGE describe different aspects of CAD, combining the diagnostic information of CMRMPI and LGE can provide incremental prognostic association with adverse cardiac events during follow-up.
Editorial see p 1342
Clinical Perspective on p 1400
We studied 264 patients (156 men; mean age ±SD, 56±13 years) referred to undergo CMRMPI. Presenting signs and symptoms categorized by the Diamond et al criteria2 included typical angina (n=37), atypical angina (n=129), and nonanginal symptoms (n=88). We determined the age- and gender-specific pretest likelihood of CAD by the combined Diamond et al and Coronary Artery Surgery Study (CASS) registry recommended by the American College of Cardiology/American Heart Association (ACC/AHA) 2002 guideline.3–5 Patients who had a history of CAD at the time of CMR referral were not excluded. Patients were excluded from CMR if they had acute chest pain consistent with unstable angina, decompensated heart failure, hemodynamic instability, a history of contraindication to vasodilator use, or metallic hazards. Medical history was obtained immediately before the CMR. Since June 2006, patients with renal dysfunction also were excluded if their serum glomerular filtration rate within the prior 30 days was ≤30 mL · min−1 · 1.73 m−2. Hypertension, hypercholesterolemia, diabetes mellitus, family history of premature CAD, and coronary risk factors were defined by published criteria.6 Significant smoking was defined by current smoking or prior tobacco use of >10 pack-years. Patients provided informed consent before the CMR. Our institutional ethics committee approved the study for patient follow-up.
Vasodilator Stress CMR Perfusion and LGE Imaging Protocol
Patients underwent CMR supine in a 1.5-T scanner (Signa CV/i, General Electric Healthcare, Waukesha, Wis) with an 8-element cardiac phased-array receiver coil. Cine steady-state free-precession (typical repetition time, 3.4 ms; echo time, 1.2 ms; temporal resolution, 40 to 50 ms; in-plane spatial resolution, ≈1.5×2.0 mm) was used for imaging left ventricular (LV) size and function in parallel short-axis views (slice thickness, 8 mm with 0-mm spacing) and 3 radial long-axis views. Patients were instructed to refrain from caffeine, tobacco, and medications such as aminophylline for 24 hours before CMR and were kept in a >4-hour fasted state. For CMRMPI, a T1-weighted notched saturation fast gradient echo (typical repetition time, 6 ms; echo time, 2.5 ms; field of view, 32 to 40 cm) was acquired, whereas a first-pass bolus of contrast (gadolinium-DTPA, Magnevist, Berlex, Wayne, NJ) was injected (0.075 to 0.1 mmol/kg at 5 mL/s) during peak vasodilatation. Adenosine was the vasodilating agent of choice, but dipyridamole was used in 30 cases (11%) when requested by the referral physicians. Adenosine was administered intravenously at 140 μg · kg−1 · min−1 over 6 minutes, and CMRMPI was acquired during the last minute of the infusion. Dipyridamole was infused at 0.56 mg · kg−1 · min−1 over 4 minutes with an additional dose of 0.28 mg · kg−1 · min−1 to achieve a 10% heart rate increase from baseline within a 3-minute interval after the infusion. CMRMPI was acquired when a 10% heart rate increase was observed or at 3 minutes after dipyridamole infusion. Although most CMRMPIs were performed with 6 to 9 short-axis locations acquired over every other heartbeat, early in the study period, CMRMPI was acquired from 4 to 5 slice locations over every heartbeat. At least 10 minutes after the stress CMRMPI, we acquired resting CMRMPI with an additional bolus of gadolinium (0.075 to 0.1 mmol/kg at 5 mL/s) using matching slice locations and pulse sequence. When dipyridamole was used, rest perfusion was performed first followed by stress perfusion >10 minutes later. LGE imaging was performed using a previously described inversion recovery pulse sequence7 at locations matching cine function, starting at 10 minutes after the second CMRMPI. We optimized the inversion time (200 to 300 ms) to achieve a signal intensity of <10 in the anteroseptal wall. The total CMR scan time was ≈50 minutes.
CMR Image Analysis
All images were analyzed with specialized software (CineTool 5.43, GE Healthcare) by researchers blinded to outcome. Epicardial and endocardial borders at end systole and end diastole were traced manually to determine the LV ejection fraction (LVEF), end-diastolic volume (LVEDV), end-systolic volume (LVESV), and end-diastolic LV myocardial mass and indexed to body surface area when appropriate.8 LVEF was calculated with the standard Simpson’s rule.9 For CMRMPI, 2 readers (R.Y.K., K.E.S.) jointly interpreted rest and stress CMRMPI (side-by-side display) in a subsequent session while blinded to clinical information, patient outcome, cine LV function, and LGE data. Using the ACC/AHA 17-segment nomenclature,10 we interpreted segmental perfusion as normal or abnormal. Each segmental perfusion was scored on the basis of the transmural extent of any perfusion defect (0= no defect, 1=1% to 25%, 2=26% to 50%, 3=51% to 75%, and 4=76% to 100%). CMRMPI of the apical cap (segment 17) could not be assessed because of the short-axis acquisition, so this segment was treated as missing. A perfusion defect was significant only if it persisted beyond peak myocardial enhancement. When uncertainty existed, we derived signal-intensity-versus-time curves from a remote region to determine the time frame of peak myocardial enhancement. Presence of a RevPD was defined by any segmental worsening of the transmural score during stress by ≥1 compared with at rest. Summed stress and rest scores were calculated by summing up the transmural scores of all 16 segments from stress and rest CMRMPI, respectively, and their difference yielded the summed difference score (SDS). Perfusion defects that were not reversible and did not demonstrate any LGE in the same segment were considered artifacts. In a session separate from the CMRMPI reading, any segmental presence of endocardial LGE (LV apical cap included) consistent with MI was recorded using the same ACC/AHA 17-segment nomenclature. Infarct mass was quantified with a semiautomated algorithm using signal intensity >2 SD above the mean signal intensity of a remote myocardial region.11–13
For both CMRMPI and LGE, corresponding coronary assignments were based on the same ACC/AHA 17-segment nomenclature.14 RevPD in the left anterior descending artery (RevPDLAD), left circumflex artery (RevPDLCx), and right coronary artery (RevPDRCA) territories were all binary variables (presence or absence of RevPD). A similar coronary assignment was used for LGE (LGELAD, LGELCx, and LGERCA, respectively).
Quantitative Coronary Angiography
Coronary angiography was performed at the discretion of the attending cardiologists. An experienced interventional cardiologist performed quantitative coronary angiographic (QCA) analysis blinded to the patient’s history and clinical outcome. Two orthogonal views of each Bypass Angioplasty Revascularization Investigation–defined segment were used to detect significant stenosis (QCAStenosis), which was defined by ≥70% luminal narrowing in the more severe view (≥50% for left main stenosis).
Follow-Up of Clinical Events
At least 6 months after the CMR, we contacted patients either telephone or mailed questionnaire, hospital chart review, and/or correspondence with the patient’s physicians. We also obtained institutional approval to search an electronic data registry for patient hospitalization after the CMR. For patients who could not be contacted, we referenced patient survival and cause of death from the Social Security Death Index and any available death certificates provided by the Commonwealth of Massachusetts. We considered the following major adverse cardiac events (MACEs): cardiac death, new acute MI, unstable angina hospitalization, and coronary revascularization performed beyond 30 days. We further defined cardiac death or new acute MI (death/MI) as an end point of interest. Death was considered cardiac if it was preceded by acute MI, acute or exacerbation of cardiac failure, or documented fatal arrhythmia. Any other unexpected death without a noncardiac cause was also considered cardiac. New MI was defined by hospitalization with symptoms consistent with acute MI and elevation of serum troponins of >2-fold in a temporal profile consistent with acute MI. When a patient experienced >1 event, the first event was chosen. Although patients who died of noncardiac causes were censored at the time of death, early (within 30 days after CMR) coronary revascularizations were not used as censoring events. CMR results, including RevPD and LGE, were made available to the ordering physicians on the day of the CMR.
Prognostic Association of RevPD and LGE With Death/MI and MACEs
Demographic data were compared by Student t or Fisher exact test with regard to RevPD presence. Kaplan–Meier distributions for death/MI, stratified by the presence of RevPD and LGE, were compared by log-rank tests. To assess for any prognostic implication of the extent and severity of RevPD, we categorized SDS into tertiles and assessed the unadjusted hazard ratio (HR) within each SDS tertile to MACEs. Presence of LGE and presence of LGE without a history of MI were coded as 2 separate variables in any model selection. To build the best final model for death/MI and MACEs, we performed multivariable Cox proportional-hazards regression analysis using a stepwise-forward selection with P=0.01 as the criteria for model entry or stay. In addition, to determine whether RevPD and LGE could provide complementary prognostic association with MACEs, we built a model that included patient age, gender, and LV systolic function and then entered both RevPD and LGE into the model. This approach would determine whether RevPD and LGE could maintain prognostic significance adjusted not only for each other but also for important clinical risk markers such as age, gender, and LV function.
Detection of QCA Stenosis or Death/MI
We also evaluated the association of RevPD by CMR to angiographic diagnosis of QCAStenosis in the first 12 months after CMR. Because verification bias existed in subsequent referral to coronary angiography, we used clinical events (cardiac death or new MI) within the first 12 months after CMR as an arbiter in patients who did not undergo invasive angiography. Sensitivities and specificities by RevPD and LGE to detect QCAStenosis or death/MI combined at 12 months were calculated. We first determined, after adjustment for age, gender, and LV systolic function, whether RevPD and LGE provided complementary association with QCAStenosis/MACE12months. We performed stepwise forward logistic regression to select the strongest set of covariates that formed the best final model in predicting QCAStenosis or MACEs within the first 12 months after CMR (QCAStenosis/MACE12months). Models were compared by model likelihood χ2). Receiver-operating characteristics curves were constructed from these respective models and were compared by use of c statistics. To prevent overfitting, the ratio of number of events to covariates was kept at ≥5 in all models. In each final multivariable model, the validity of the proportional-hazards assumption was tested by adding a time-dependent interaction variable for each of the covariates in the model. For all analyses, a value of P<0.05 was used to define statistical significance. All analyses were performed with SAS 9.1 (SAS Institute, Cary, NC) for Windows.
Of the initial 264 patients, 10 patients were excluded because of technical problems, including 6 patients with claustrophobia and 4 patients who were unable to complete adenosine infusion because of intolerable side effects. Table 1 summarizes the baseline characteristics and CMR findings of the remaining 254 patients (150 men; mean age, 58±13 years) who formed the study cohort. Patients in the cohort carried an intermediate pretest coronary risk profile: 57%, 25%, and 22% had a history of hypertension, diabetes mellitus, and prior infarction, respectively. There were no complications except 1 case of self-terminated atrial flutter during vasodilator infusion. Patients experienced an average of a 29% increase in heart rate and a 6% drop in systolic blood pressure during stress. Seventy-four patients (29%) demonstrated RevPD by CMR. Although the average LVEF and LVEDV index of the study cohort were within normal ranges, patients with RevPD were older and had more coronary risk factors, higher pretest CAD likelihood, lower LVEF, and higher ventricular mass and LVEDV index.
Association of Presence and Extent of RevPD and LGE With Death/MI and MACEs
Clinical follow-up was successful in all 254 patients (100%). After a median follow-up of 17 months (range, 8 months to 4.7 years), there were 49 events, including 12 cardiac deaths, 16 acute MIs, 19 unstable anginal hospitalizations, and 2 cases of late coronary revascularization. Another 6 patients died of noncardiac causes and were censored on the day of death. By univariable analysis (Table 2⇓), the presence of RevPD and LGE demonstrated strong association with both death/MI (HR, 6.88 and 5.31, respectively; both P<0.0001) and MACEs (HR, 10.92 and 8.09, respectively; both P<0.0001). The Kaplan–Meier curves corresponding to these associations are shown in Figure 1A and 1B for death/MI and Figure 1C and 1D for MACEs. By quantitative analysis, the myocardial extent of RevPD and infarct mass by LGE were also strong predictors of both death/MI and MACEs. SDS demonstrated significant association with death/MI and was the strongest univariable predictor for MACEs (model likelihood χ2=36.94; P<0.0001). For every SDS gained, hazards for MACEs increased on average by 8%. The model likelihood χ2 for association with death/MI (Figure 2A) and MACEs (Figure 2B) became progressively higher from the lowest to the highest SDS tertile (compared with patients outside the tertile of interest) with a mean SDS that ranged from 1.8 (lowest tertile) to 16.9 (highest tertile), indicating a progressively stronger association of increasing SDS with death/MI and MACEs, respectively.
Best Final Models for Death/MI and MACEs
Table 3 demonstrates the best final model for death/MI by stepwise forward selection that included LVESV index and heavy tobacco use. Table 3 also demonstrates the best final model for MACEs. The only variables selected include RevPD and pretest CAD likelihood (Diamond et al and CASS criteria). RevPD was the strongest multivariable predictor for MACEs. Adjusted to a pretest likelihood of CAD, RevPD maintained a >8-fold hazards increase for MACEs (adjusted HR, 8.61; P<0.0001).
Complementary Prognostic Roles of RevPD and LGE Adjusted to Patient Age and Gender
When RevPD and LGE were entered into a model that included age and gender, RevPD and LGE each maintained a strong association with death/MI. RevPD maintained a 3.3-fold hazards increase in death/MI when adjusted for the effects of age, gender, and LGE, whereas LGE maintained a 3.4-fold hazards increase in death/MI when adjusted for the effects of age, gender, and RevPD (P=0.02 and 0.01, respectively). This similar pattern was also observed in the association with MACEs. RevPD maintained a 5.5-fold hazards increase in MACEs when adjusted for the effects of age, gender, and LGE (P=0.0004), whereas LGE maintained a 2.7-fold hazards increase in MACEs when adjusted for the effects of age, gender, and RevPD (P=0.04). Figure 3 illustrates the Kaplan–Meier event-free survival curves stratified by RevPD or LGE after these adjustments. The complementary prognostic roles of RevPD and LGE demonstrated by these models were not altered by early revascularization (within the first 30 days after CMR). When early revascularization was used as a stratification factor and adjustment was made for patient age, gender, and LGE presence, RevPD maintained a close to 3-fold hazard for death/MI (adjusted HR, 2.85; P=0.05) and a >4-fold hazard for MACEs (adjusted HR, 4.35; P=0.003). On the other hand, with early revascularization stratified and patient age, gender, and RevPD adjusted, LGE maintained a >3-fold hazard for death/MI and MACEs (adjusted HR, 3.70; P=0.01; and adjusted HR, 3.27; P=0.02, respectively). Although LVESV index is a known robust risk marker for MACEs, when it was added into the multivariable model for MACEs, the respective prognostic association of RevPD and LGE was not affected: RevPD maintained a 6.3-fold and LGE maintained a 2.7-fold hazards increase in MACEs when each was adjusted for all other variables in the model (P=0.0002 and P=0.04, respectively). In 179 patients (70%) in whom LGE was absent, RevPD presence indicated a 17-fold and a 14-fold increase in hazards for death/MI and MACEs, respectively, adjusted for age and gender (P=0.0005 and P<0.0001, respectively). By stepwise forward selection, RevPD was the strongest multivariable predictor of death/MI and MACEs in patients without LGE. In 180 patients (71%) in whom RevPD was absent, LGE presence indicated a 13-fold and 9-fold increase in hazards for death/MI and MACEs, respectively, adjusted for age and gender (P=0.0002 and P=0.002, respectively). Three patients without LGE had resting perfusion defects that were not reversible. None of these 3 patients experienced MACEs.
Figure 4 displayed the annual event rates for death/MI and MACEs in the study cohort. The presence of both RevPD and LGE portended elevated annual event rates of death/MI (19% and 23%, respectively) or MACEs (38% and 45%, respectively). Patients who demonstrated both RevPD and LGE had event rates of death/MI and MACEs of 21% and 48%, respectively. Patients with both RevPD and LGE absent had the lowest event rates of death/MI and MACEs.
Subgroup Analysis in Patients Without a History of MI
Of the 198 patients (78%) who had no history of MI, 27 had LGE consistent with unrecognized MI. Twenty-seven patients (14%) experienced MACEs, including 9 cardiac deaths, 9 acute MIs, 9 unstable angina hospitalizations, and no late revascularization. RevPD and LGE both demonstrated strong unadjusted association with death/MI (HR, 9.03; P<0.0001; and HR, 6.06; P=0.0003, respectively) and MACEs (HR, 16.22 and 10.31, respectively; both P<0.0001). By stepwise forward selection, RevPD was selected to form the best final models for death/MI and MACEs, and it was the strongest multivariable predictor of MACEs. Figure 5 shows the Kaplan–Meier curves illustrating complementary prognostic associations of RevPD and LGE with clinical events in patients without a history of MI. Both RevPD and LGE were associated with reduced death/MI-free survival (Figure 5A and 5B). Although RevPD also demonstrated strong association with reduced MACE-free survival (Figure 5C), patients with both LGE and RevPD experienced the worst MACE-free survival distribution (Figure 5D). In patients without a history of MI, both RevPD and LGE demonstrated strong univariable association with death/MI (HR, 9.03 and 6.06; P<0.0001 and P=0.0003, respectively) and MACEs (HR, 16.22 and 10.31, respectively; both P<0.0001). By multivariable analyses, RevPD and LGE maintained strong association with death/MI and MACEs after adjustment for the effects of age and gender and for each other. When age, gender, RevPD, and LGE were entered into a model for death/MI, RevPD and LGE both demonstrated independent prognostic association (adjusted HRs, 4.52 and 3.72, respectively; both P=0.02). When age, gender, RevPD, and LGE were entered into a model for MACEs, presence of RevPD demonstrated independent prognostic association (adjusted HRs, 8.92; P=0.0008), whereas LGE showed a trend toward independent association (adjusted HRs, 3.00; P=0.07). In 156 patients without a history of MI who did not demonstrate RevPD, LGE presence indicated a >11-fold elevated hazards for death/MI (HR, 11.48; P=0.001). Figure 6 displayed the annual event rates of death/MI or MACEs in patients without a history of MI. A presence of RevPD and LGE was both associated with high rates of death/MI (18% and 31%, respectively, versus 3.8%) and MACEs (30% and 50%, respectively, versus 4.7% and 5.5%, respectively). In patients without a history of MI, patients who had both RevPD and LGE had high rates of death/MI (27%) and MACEs (60%), a stark comparison to the low annual rates in death/MI (2%) or MACEs (3.1%) among patients with absent RevPD and LGE.
Diagnosing QCAStenosis by RevPD With and Without LGE
At the discretion of the referring physician, 68 patients (27%) underwent x-ray coronary angiography within the first 12 months after CMR, with 43 patients (63%) demonstrating QCAstenosis; among them, 20 patients underwent percutaneous revascularization. RevPD was present in 40 of the 43 patients with QCAstenosis (sensitivity, 93%) and was normal in 21 of the 25 patients without QCAstenosis (specificity, 84%). Adding the presence of LGE detected 1 additional case of QCAstenosis (sensitivity increased to 95%) but at the expense of 4 “false-positive” cases without QCAstenosis (specificity dropped to 70%). RevPD detects single-vessel, 2-vessel, and 3-vessel QCAstenosis at sensitivities of 92%, 94%, and 100%, respectively. In the 186 patients who were not referred to undergo coronary angiography, 12 patients experienced MACEs within the first 12 months after CMR (3 cardiac deaths, 5 acute MIs, 3 hospitalizations for unstable angina, and 1 late revascularization). Figure 7 illustrates the best final multivariable model for QCAstenosis/MACE12months using stepwise forward selection. This model, which selected RevPD, LGE, and other variables as shown, yielded a 91% area under the curve in its association with QCAstenosis/MACE12months.
Consistent with recent reports, in this study, the presence and the extent of RevPD by CMR stress perfusion imaging provide excellent prognostic stratification of patients with known or suspected CAD. However, our study provides new and important findings: RevPD and LGE provide complementary prognostication for death/MI in patients referred to CMR for assessment of known or suspected CAD. This is evident by the fact that both RevPD and LGE maintained a >3-fold association with death/MI when adjusted for each other and for the effects of patient age and gender (adjusted HR, 3.31; P=0.02; and adjusted HR, 3.43; P=0.01, respectively). We also found that although RevPD was the strongest multivariable predictor selected for MACEs, those with both RevPD and LGE absent had the lowest annual event rates of death/MI and MACEs (<2% and <3%, respectively).
Several studies have shown strong prognostic value of CMR perfusion imaging. Ingkanisorn et al15 and Aletras et al16 studied chest pain patients in the emergency room and reported excellent cardiac event–free survival among patients with negative vasodilating stress CMRMPI. Jahnke et al1 reported that in 513 patients with abnormal adenosine, CMRMPI portended a 12-fold increased risk for cardiac events, whereas a normal combined examination portended a 3-year event-free survival of 99%. However, these studies did not assess the relative or incremental prognostic value of LGE available from the same imaging session. Although RevPD is sensitive to alteration of regional blood flow secondary to coronary stenosis, LGE can detect and quantify a broad range of infarction with or without a clinical knowledge of prior MI. It is therefore conceivable that this observed complementary prognostic association by RevPD and LGE is due to their characterization of different pathological alteration of myocardial physiology after CAD. In this regard, it is consistent with our observation that LGE as evidence of prior infarction was associated with hard events such as new MI or cardiac death, whereas RevPD as evidence of flow-limiting coronary stenosis was associated with less critical events such as unstable angina. LGE without a history of MI most likely indicates an untreated coronary event resulting in subclinical infarction, supported by the >11-fold adjusted hazards increase for death/MI despite an absence of RevPD in the present study. Although patients who had CMR positive for RevPD and LGE represented the highest-risk group and experienced a >20% annual rate of death/MI, patients with CMR negative for both RevPD and LGE had a favorable negative event rate for death/MI of >98%. On the other hand, LGE data did not significantly improve the detection of QCAStenosis evidenced on x-ray angiography by RevPD. Unrecognized MI as detected by LGE can occur as the result of a spontaneous thrombolysis and recannulation of an acute coronary lesion. Thus, although LGE provides a footprint of myocardial damage caused by a prior coronary event, it may not be associated with a flow-limiting coronary lesion.
Some selection bias exists from the pattern for CMR referral at our institution; thus, the prevalence of CAD in our cohort appeared high compared with other similar studies. Although we also demonstrated that the current strong prognosticating potentials offered by CMR perfusion and LGE imaging were robust and consistent in the subgroup of patients without a history of MI, future studies need to determine whether the present results may be extrapolated to the same degree in a population with substantially lower CAD prevalence. Another limitation relates to the small subset of patients with angiographic verification of coronary stenosis; therefore, test specificity can only be estimated on the basis of limited data. The principal aim of our study was to evaluate the prognostic value of clinical and CMR data, not its ability to detect anatomic CAD. Finally, we did not collect analogous patient data from stress nuclear myocardial perfusion imaging or computed tomography angiography and therefore cannot comment on the relative clinical value of these imaging modalities compared with CMR for the evaluation of patients presenting for evaluation of cardiac ischemic symptoms.
In patients with known or suspected CAD, the present study provides evidence in support of robust and complementary roles from perfusion and LGE imaging by CMR in risk stratifying against cardiac death or MI.
Sources of Funding
This study was supported by the Brigham and Women’s Hospital Cardiovascular Imaging Funds. Dr Kwong is supported in part by a research grant from the National Institutes of Health (NIH RO1 HL091157).
Jahnke C, Nagel E, Gebker R, Kokocinski T, Kelle S, Manka R, Fleck E, Paetsch I. Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 2007; 115: 1769–1776.
Chaitman BR, Bourassa MG, Davis K, Rogers WJ, Tyras DH, Berger R, Kennedy JW, Fisher L, Judkins MP, Mock MB, Killip T. Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation. 1981; 64: 360–367.
Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Fihn SD, Fraker TD Jr, Gardin JM, O'Rourke RA, Pasternak RC, Williams SV. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). J Am Coll Cardiol. 2003; 41: 159–168.
Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106: 3143–3421.
Salton CJ, Chuang ML, O'Donnell CJ, Kupka MJ, Larson MG, Kissinger KV, Edelman RR, Levy D, Manning WJ. Gender differences and normal left ventricular anatomy in an adult population free of hypertension: a cardiovascular magnetic resonance study of the Framingham Heart Study Offspring cohort. J Am Coll Cardiol. 2002; 39: 1055–1060.
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. 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. Circulation. 2002; 105: 539–542.
Kwong RY, Chan AK, Brown KA, Chan CW, Reynolds HG, Tsang S, Davis RB. 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.
Gerber BL, Garot J, Bluemke DA, Wu KC, Lima JA. Accuracy of contrast-enhanced magnetic resonance imaging in predicting improvement of regional myocardial function in patients after acute myocardial infarction. Circulation. 2002; 106: 1083–1089.
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. 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.
Cardiac magnetic resonance (CMR) reversible myocardial perfusion defect (RevPD) has demonstrated not only high accuracy in detection of flow-limiting coronary stenosis but also strong prognostic value in risk stratifying patients presenting with suspected ischemia. With high tissue contrast and spatial resolution, CMR late gadolinium enhancement (LGE) imaging is the most sensitive current imaging technique for detecting small subendocardial infarction that elevates a patient’s risk of cardiac events. In a clinical cohort of 254 patients referred for stress CMR imaging, we tested the hypothesis that RevPD and LGE imaging in a single CMR study can provide complementary prognostic values for major adverse events, including cardiac death or nonfatal myocardial infarction (MI). Although RevPD and LGE both demonstrated strong unadjusted association with death/MI (hazard ratio, 6.88 and 5.32, respectively; both P<0.0001), robust association with death/MI by RevPD and LGE was maintained when the effects of these variables were adjusted for each other and for patient age and gender. In patients without a history of MI who were found to have no RevPD, the presence of LGE portended a >11-fold hazards increase in death/MI. We found that patients with both RevPD and LGE absent had the most favorable annual negative event rate for death/MI at >98%. We therefore conclude that CMR stress myocardial perfusion and LGE imaging performed in a CMR study provide complementary prognostic implication for cardiac death or acute nonfatal MI.
Guest Editor for this article was Robert O. Bonow, MD.