Coronary artery disease (CAD) is a leading cause of mortality worldwide [
Cardiovascular magnetic resonance (CMR) is an established, robust, noninvasive, and radiation-free imaging technique for assessing CAD [
Therefore, the aim of our study was twofold: (1) to assess whether, in a large, well-characterized population with optimal medical therapy undergoing CMR for stable CAD, the presence of left ventricle (LV) dysfunction, SPCMR abnormalities, and/or fibrosis (assessed by LGE) was independent predictor of all-cause mortality in the long term, independently of traditional cardiovascular risk factors and (2) to assess the prognostic impact of CMR on major adverse cardiovascular events (MACE).
We performed a single centre, observational prospective study. Inclusion criteria: consecutive patients referred clinically for CMR with either definite diagnosis or a history suggesting stable CAD were enrolled. Exclusion criteria: we excluded patients with recent acute coronary syndrome (within 6 weeks), previous hospitalization for heart failure (NYHA class IV or need of infusive therapy) and signs of myocarditis, infiltrative or hypertrophic cardiomyopathy, and pericardial disease. Part of the study cohort participated in an earlier study on independent prognostic value of LGE [
Informed consent to participate in the research study was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institutional Review Board of the Fondazione Salvatore Maugeri (Pavia, Italy).
Follow-up visits were conducted at our centre every 1–24 months, depending on clinical severity. Telephonic follow-up was performed for those patients whose last visit date was 6 months prior to the database closure. The primary outcome measure was all-cause mortality. The secondary outcome measure was a composite clinical endpoint of MACE, including all-cause mortality and hospitalization due to new onset New York Heart Association (NYHA) class IV or needing intravenous diuretics for heart failure, acute coronary syndrome (ACS), or myocardial revascularization procedures. Revascularization occurring within one month of CMR imaging was considered as CMR related and was not calculated as a separate MACE. Cases with more than one MACE were censored at the time of the first event.
Categorical variables were expressed as counts and percentage, continuous variables as mean ± standard deviation or interquartile range (IQR). Two-sided P<0.05 was the significance level for hypothesis testing and SPSS Statistics 18.0 (IBM, USA) was the statistical package used. Differences at baseline between patients with and without events were tested with Pearson
Five hundred eighty-nine patients were referred to our unit for CMR assessment during the period of interest. Forty-five (8%) were excluded as they presented exclusion criteria, and 54 (9%) because stress perfusion was not performed for clinical reason. Twenty-five (4%) patients were lost to follow-up. Thus, 465 patients entered the study, 397 (85%) with a definite diagnosis of CAD at enrollment and 68 (15%) with a history of likely CAD (Figure
Main baseline characteristics are reported in Table
Baseline characteristics and differences between patients without and with primary outcome. (all-cause mortality).
| | | | |
---|---|---|---|---|
| | | ||
ANTHROPOMETRY | ||||
Age (years) | 63 ± 11 | 63 ± 11 | 67 ± 10 | 0.006 |
Male sex | 372 (80%) | 334 (81%) | 38 (76%) | 0.454 |
Body mass index (kg/m2) | 26 ± 4 | 26 ± 4 | 26 ± 5 | 0.088 |
CAD RISK FACTORS | ||||
Family history of CAD | 201 (43%) | 183 (44%) | 18 (38%) | 0.454 |
Smoking | 283 (61%) | 245 (59%) | 38 (76%) | 0.018 |
Diabetes | 88 (19%) | 75 (18%) | 13 (26%) | 0.170 |
Hypertension | 267 (57%) | 238 (57%) | 29 (57%) | 0.417 |
Hypercholesterolemia | 271 (58%) | 241 (58%) | 30 (60%) | 0.763 |
No. of CV risk factors | 2.4 ± 1.2 | 2.4 ± 1.2 | 2.6 ± 1.0 | 0.358 |
CLINIC HISTORY | ||||
Previous CAD diagnosis | 398 (86%) | 350 (84%) | 48 (96%) | 0.027 |
Previous myocardial infarction | 298 (64%) | 257 (62%) | 41 (82%) | 0.005 |
LM or 3-vessel CAD | 165 (35%) | 144 (35%) | 21 (42%) | 0.292 |
NYHA classification (III class) | 15 (3%) | 11 (3%) | 4 (8%) | 0.111 |
Revascularization in the follow-up | 112 (24%) | 106 (26%) | 6 (12%) | 0.032 |
PHARMACOLOGICAL THERAPY | ||||
| 361 (78%) | 321 (78%) | 40 (80%) | 0.692 |
Ca++-antagonist | 97 (21%) | 85 (21%) | 12 (24%) | 0.563 |
Nitrates | 184 (40%) | 161 (39%) | 23 (46%) | 0.325 |
Loop diuretics | 146 (31%) | 122 (29%) | 24 (48%) | 0.007 |
Aldosterone antagonist | 54 (12%) | 44 (11%) | 10 (20%) | 0.050 |
ACE-inhibitors/ARB | 369 (79%) | 330 (80%) | 39 (78%) | 0.802 |
ASA | 396 (85%) | 351 (85%) | 45 (90%) | 0.308 |
Statins | 355 (76%) | 317 (76%) | 38 (76%) | 0.952 |
Anticoagulant use | 28 (6%) | 22 (5%) | 6 (12%) | 0.117 |
ECG | ||||
Heart rate (bpm) | 64 ± 12 | 64 ± 11 | 70 ± 14 | <0.001 |
Non sinus rhythm | 14 (3%) | 11 (3%) | 3 (6%) | 0.317 |
QRS duration (msec) | 104 ± 19 | 103 ± 18 | 111 ± 24 | 0.021 |
QTc interval (msec) | 423 ± 31 | 421 ± 31 | 436 ± 33 | 0.002 |
LV hypertrophy | 66 (14%) | 57 (14%) | 9 (18%) | 0.440 |
LBBB | 55 (12%) | 43 (10%) | 12 (24%) | 0.005 |
RBBB | 59 (13%) | 51 (12%) | 8 (16%) | 0.486 |
ST segment depression | 28 (6%) | 24 (6%) | 4 (8%) | 0.758 |
Negative T waves | 217 (47%) | 186 (45%) | 31 (62%) | 0.021 |
Q waves | 178 (38%) | 158 (38%) | 20 (41%) | 0.660 |
ECHOCARDIOGRAPHY | ||||
LVEDV (ml/m2) | 60 ± 30 | 58 ± 29 | 72 ± 29 | 0.006 |
LVESV (ml/m2) | 29 ± 17 | 27 ± 15 | 44 ± 26 | <0.001 |
LVEF (%) | 53 ± 13 | 54 ± 12 | 43 ± 14 | <0.001 |
LVWMSI | 1.4 ± 0.4 | 1.3 ± 0.4 | 1.7 ± 0.5 | <0.001 |
LV mass (g) | 197 ± 64 | 195 ± 61 | 220 ± 86 | 0.053 |
LV diastolic dysfunction (≥pseudo-normal) | 42 (9%) | 34 (8%) | 8 (16%) | 0.119 |
Mitral regurgitation (≥ moderate) | 65 (14%) | 51 (12%) | 14 (27%) | 0.006 |
Pulmonary hypertension (sPAP>35 mmHg) | 34 (7%) | 27 (8%) | 7 (14%) | 0.102 |
RVIT dilatation (>40 mm) | 30 (7%) | 27 (7%) | 3 (6%) | 1.000 |
RV dysfunction (TAPSE<15 mm) | 35 (8%) | 28 (7%) | 7 (14%) | 0.122 |
CARDIAC MAGNETIC RESONANCE | ||||
CMR LVEF (%) | 54 ± 15 | 56 ± 14 | 43 ± 18 | <0.001 |
CMR LV mass (g) | 153 ± 40 | 151 ± 37 | 174 ± 55 | 0.006 |
CMR LVEDV (ml/m2) | 70 ± 46 | 69 ± 47 | 85 ± 37 | 0.014 |
CMR LGE (% of LV mass) | 11 ± 13 | 10 ± 12 | 19 ± 18 | <0.001 |
CMR myocardial stress induced perfusion abnormality | 82 (18%) | 73 (18%) | 9 (18%) | 0.943 |
CAD = coronary artery disease; CV = cardiovascular; LM = left main; NYHA = New York heart association; ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; ASA = acetylsalicylic acid; QTc = corrected QT; LBBB = left bundle branch block; RBBB = right bundle branch block; LVEDV = left ventricle end diastolic volume, LVESV = left ventricle end systolic volume; LVEF = left ventricle ejection fraction; LVWMSI = left ventricle wall motion score index; TAPSE = tricuspid annular plane systolic excursion; RVIT = right ventricle inflow tract; CMR = cardiac magnetic resonance; LGE = late gadolinium enhancement.
Univariate Cox analysis of conventional assessment and CMR metrics for all-cause mortality and MACE.
| | |||
---|---|---|---|---|
Hazard Ratio (95%CI) | | Hazard Ratio (95%CI) | | |
ANTHROPOMETRIC | ||||
Age (≥75 years) | 2.6 (1.4−4.9) | 0.003 | 1.6 (1.0−2.4) | 0.036 |
Male sex | 1.1 (0.8−1.5) | 0.577 | 1.0 (0.8−1.2) | 0.674 |
Body mass index (>30) | 1.5 (0.8−3.0) | 0.244 | 1.1 (0.7−1.8) | 0.668 |
RISK FACTORS | ||||
Family history of CAD | 0.8 (0.4−1.4) | 0.391 | 0.9 (0.6−1.3) | 0.609 |
Smoking (previous or active) | 2.2 (1.2−3.5) | 0.017 | 1.7 (1.2−2.3) | 0.005 |
Diabetes | 1.4 (1.2−4.2) | 0.206 | 1.5 (1.0−2.1) | 0.056 |
Hypertension | 0.8 (0.5−1.4) | 0.488 | 1.1 (0.8−1.6) | 0.448 |
Hypercholesterolemia | 1.1 (0.6−2.2) | 0.714 | 1.2 (0.9−1.8) | 0.258 |
No. of CV risk factors (≥3) | 1.5 (0.8−2.6) | 0.168 | 1.6 (1.1−2.2) | 0.013 |
CLINIC | ||||
Previous CAD diagnosis | 4,2 (1.0−17.3) | 0.046 | 2.4 (1.3−4.6) | 0.007 |
Previous myocardial infarction | 2.7 (1.3−5.6) | 0.006 | 1.2 (0.8−1.7) | 0.392 |
LM or 3-vessel CAD | 1.5 (0.8−2.6) | 0.166 | 2.3 (1.6−3.2) | <0.001 |
NYHA classification (≥III) | 3.3 (1.2−9.2) | 0.022 | 2.5 (1.2−5.4) | 0.018 |
Revascularization in the follow-up | 0.4 (0.2−0.9) | 0.037 | - | |
ACS in the follow-up | 4.9 (2.2−10.8) | <0.001 | - | |
THERAPY | ||||
| 1.2 (0.6−2.3) | 0.536 | 1.0 (0.7−1.5) | 0.941 |
Ca++-antagonist | 1.2 (0.6−2.3) | 0.536 | 1.1 (0.7−1.7) | 0.556 |
Nitrates | 1.3 (0.7−2.2) | 0.380 | 1.1 (0.8−1.6) | 0.473 |
Loop diuretics | 2.2 (1.3−3.9) | 0.005 | 1.5 (1.1−2.2) | 0.021 |
Aldosterone antagonist | 2.4 (1.2−4.8) | 0.013 | 1.4 (0.9−2.3) | 0.158 |
ACE-inhibitors/ARB | 0.9 (0.5−1.8) | 0.841 | 1.3 (0.8−2.0) | 0.297 |
ASA | 1.7 (0.7−4.3) | 0.262 | 1.3 (0.8−2.2) | 0.253 |
Statins | 1.0 (0.5−2.0) | 0.943 | 1.0 (0.6−1.4) | 0.831 |
Anticoagulant | 2.3 (1.0−5.5) | 0.053 | 1.9 (1.1−4.4) | 0.027 |
ECG | ||||
Heart rate (>75 bpm) | 2.3 (1.2−4.3) | 0.011 | 1.7 (1.1−2.6) | 0.018 |
Non sinus rhythm | 2.8 (0.9−9.1) | 0.082 | 2.2 (1.0−4.8) | 0.038 |
QRS duration (>120 msec) | 3.4 (1.9−6.3) | <0.001 | 2.1 (1.4−3.3) | <0.001 |
QTc interval (≥460 msec) | 3.3 (1.8−6.2) | <0.001 | 1.6 (1.0−2.6) | 0.035 |
LV hypertrophy | 1.4 (0.7−2.8) | 0.380 | 1.2 (0.7−1.9) | 0.483 |
LBBB | 2.3 (1.2−4.4) | 0.013 | 1.7 (1.0−2.7) | 0.032 |
RBBB | 1.4 (0.6−2.9) | 0.431 | 1.4 (0.9−2.2) | 0.161 |
ST segment depression | 1.4 (0.5−3.8) | 0.537 | 1.7 (0.9−3.2) | 0.089 |
Negative T waves | 1.9 (1.1−3.4) | 0.028 | 1.4 (1.0−1.8) | 0.048 |
Q waves | 1.1 (0.6−1.9) | 0.774 | 1.3 (1.0−2.0) | 0.101 |
ECHOCARDIOGRAPHY | ||||
LVEDV (≥105 ml/m2)§ | 3.6 (1.7−7.7) | 0.001 | 1.4 (0.7−2.7) | 0.370 |
LVESV (≥75 ml/m2)§ | 9.4 (4.4−20.2) | <0.001 | 2.4 (1.2−4.9) | 0.016 |
LVEF (≤30%) | 8.0 (4.0−16.0) | <0.001 | 3.2 (1.9−5.5) | <0.001 |
LVWMSI (≥2.32)§ | 5.5 (2.2−13.9) | <0.001 | 3.3 (1.7−6.5) | 0.001 |
LV mass (≥310 g)§ | 4.4 (2.0−9.4) | <0.001 | 2.0 (1.1−3.6) | 0.025 |
LV diastolic dysfunction (≥pseudo-normal)† | 2.3 (1.1−4.8) | 0.035 | 1.8 (1.1−3.0) | 0.025 |
Mitral regurgitation (≥moderate)‡ | 2.5 (1.3−4.7) | 0.005 | 1.5 (0.9−2.3) | 0.098 |
Pulmonary hypertension (sPAP>35 mmHg) | 2.3 (1.0−5.1) | 0.040 | 1.7 (1.0−2.8) | 0.065 |
RVIT dilatation (>40 mm) | 1.0 (0.3−3.2) | 0.989 | 1.1 (0.5 – 2.2) | 0.892 |
RV dysfunction (TAPSE<15 mm) | 2.2 (1.0−4.9) | 0.053 | 1.1 (0.6−2.1) | 0.706 |
CMR | ||||
CMR LVEDV (≥122 ml/m2)§ | 6.7 (3.1−14.4) | <0.001 | 3.0 (1.6−5.8) | 0.001 |
CMR LVEF (<35%) | 5.4 (3.0−9.6) | <0.001 | 2.6 (1.7−4.0) | <0.001 |
CMR LV mass (≥236 g)§ | 3.5 (1.4−8.7) | 0.008 | 1.4 (0.6−3.5) | 0.443 |
CMR LGE (>40%)§ | 7.6 (3.0−19.2) | <0.001 | 5.1 (2.7−9.4) | <0.001 |
CMR myocardial stress induced perfusion abnormality | 1.1 (0.5−2.2) | 0.881 | 2.3 (1.6 – 3.5) | <0.001 |
CMR = cardiovascular magnetic resonance; MACE = major adverse cardiac events; CAD = coronary artery disease; CV = cardiovascular; LM= left main; NYHA =New York heart association; ACS = acute coronary syndrome; ACE =angiotensin converting enzyme; ARB = angiotensin receptor blocker; ASA =acetylsalicylic acid; LBBB = left bundle branch block; RBBB = right bundle branch block; LVEDV = left ventricular end diastolic volume; LVESV = left ventricular end systolic volume; LVEF = left ventricular ejection fraction; LVWMSI = left ventricular wall motion score index; LV = left ventricle/ventricular; sPAP = systolic pulmonary artery pressure; RVIT = right ventricular inflow tract; RV = right ventricle; TAPSE = tricuspid annular plane systolic excursion; LGE = late gadolinium enhancement.
† based on trans-mitral diastolic flow and pulmonary vein flow evaluation.
‡ based on effective regurgitant orifice area.
§ cut-off equal to the 95% percentile of the entire population.
Univariate analyses showed, in keeping with published literature, an association between all-cause mortality and LVEF and several other predefined factors. Among them, only a revascularization procedure after the study enrollment was a protecting factor from mortality. Univariate hazard ratios are shown in Table
Stepwise inclusion of variables reaching the predefined univariate significance value threshold (p<0.1) into a multivariate Cox model in which LVEF was included at the first step significantly improved the model predictability (extra sum of square
Univariate analyses identified many conventional variables associated with MACE. Indeed, all variables associated with all-cause mortality, except mitral regurgitation, pulmonary hypertension, and previous MI, predicted MACE as well. Moreover, LM/3-vessel CAD, atherosclerotic risk factors burden (≥3 risk factors), and nonsinus rhythm emerged as relevant predictors of MACE too. Univariate hazard ratios with 95% confidence intervals of all conventional variables are shown in Table
Multivariate analysis confirmed the prognostic relevance of LVEF (3.0
CMR metrics of LV volume, ejection fraction, and mass as well as total burden of LGE were strongly associated with all-cause mortality (LVEDV 6.7
Multivariate analysis, which introduced CMR at the last step, showed that CMR variables retain a prognostic value once LVEF at echocardiography and all other significant conventional variables have been taken into account. Indeed, CMR assessment slightly improved the model fit (
Final model of Cox multivariate analysis for all-cause mortality
Hazard Ratio | 95% CI | | |
---|---|---|---|
ACS in the follow-up | 6.7 | 2.9−15.8 | <0.001 |
LVEF on echocardiography (≤30%) | 4.2 | 2.0−9.0 | <0.001 |
QTc interval (≥460 msec) | 2.8 | 1.5−5.4 | 0.002 |
LV mass (≥220 g) | 2.9 | 1.3−6.6 | 0.009 |
TotalLGE burden (≥ 40% LV mass) | 3.4 | 1.3−8.8 | 0.012 |
Heart rate (>75 bpm) | 2.0 | 1.0−3.8 | 0.041 |
Final model of Cox multivariate analysis for MACE
Hazard Ratio | 95% CI | | |
---|---|---|---|
Total LGE burden (>40% LV mass) | 3.3 | 1.7−6.3 | <0.001 |
CMR myocardial stress induced perfusion abnormality | 2.1 | 1.4−3.2 | <0.001 |
LM or 3−vessel CAD | 1.9 | 1.4−2.8 | <0.001 |
LVEF on echocardiography (≤30%) | 2.5 | 1.4−4.4 | 0.002 |
Smoking | 1.5 | 1.0−2.2 | 0.038 |
ACS = acute coronary syndrome; LV = left ventricle; LVEF = left ventricle ejection fraction; QTc = corrected QT interval; LGE = late gadolinium enhancement; CMR = cardiovascular magnetic resonance; MACE = major adverse cardiac events; LM = left main coronary artery; CAD = coronary artery disease.
CMR parameters were strongly associated with MACE in terms of LV dimensions (LVEDV 3.0
After correction for the effect of conventional variables, introduction of CMR variables into the multivariate analysis significantly improved the model fit (
Our study aimed at assessing prognostic power of CMR in a contemporary population with stable CAD and optimal medical treatment, in which CMR was used on top of standard conventional risk assessment. Main findings of the study were as follows: (1) new evidence in the long term of prognostic relevance of LGE as an independent predictor of all-cause mortality; (2) lack of independent prognostic value of SPCMR versus all-cause mortality; (3) confirmation of independent prognostic value of a comprehensive CMR exam, including stress perfusion assessment, for the prediction of a composite endpoint of morbidity and mortality.
At the time of enrollment closure the study had 465 patients that were followed up for a median time of 5.2 years. We primarily investigated the hard endpoint of all-cause mortality. Fifty deaths were observed in the follow-up period, corresponding to a global mortality rate of 10.8% and an annualized event rate of 2.1%. For comparison, all-cause mortality in clinical trials assessing different treatment strategies in stable CAD was in the range 1.3-2.7% [
Quantification of fibrosis with LGE was confirmed to be independently associated with mortality. Replacement of large amount of myocardium with scar, namely, of more than 40 percent of LV mass, carried a mean 3.4-fold increase of risk of death after correction for all other factors, in particular LVEF. Given the length of the follow-up of our study, this finding is a confirmation in the long term of what has emerged in recent years from a series of studies showing a negative prognostic significance of myocardium replacement by fibrotic scar, beyond its effect on contractility [
Exploring predictors of all-cause mortality, we unexpectedly found that stress-induced perfusion abnormalities at CMR are not independently correlated with prognosis. This finding was quite unpredicted if we consider (1) the good sensitivity and specificity shown by SPCMR for ischemia detection, also in comparison with established imaging techniques like single photon emission tomography [
In accordance with the literature, patients with a normal SPCMR study have a 1-year mortality of less than 1%, a level of risk significantly inferior to that of patients with positive stress testing. Consequently, the reason why stress perfusion data miss their prognostic significance when SPCMR is used on top of a conventional risk stratification process, as the present study seems to suggest, is not easily understandable. In detail, we found that a significant myocardial ischemia (involving>10% of LV, in accordance with recent guidelines) is not useful to predict mortality once all other well-known significant variables from the clinical history, electrocardiogram, and echocardiography, in particular LVEF, have been considered.
Over the last few decades, significant changes occurred in medical therapy of patients with CAD and atherosclerosis in general, due to the marketing of new drugs like statins, ACE-inhibitors/ARB or thienopyridine, and the wider use of old but efficacious drugs like aspirin. Consistent results of large randomized clinical trials showing reduction of hard events [
An optimized pharmacologic treatment is methodologically important to minimize the confounding effect of a suboptimal treatment. This goal was achieved in the population we studied thanks to a general policy of guidelines implementation adopted by our department. Compared to the aforementioned clinical trials, the population we investigated had similar levels of treatment with statins (76% versus 73-95%), ASA (85% versus 80-96%), and ACE-inhibitors/ARB (79% versus 30-92%).
Bearing in mind these considerations, the lack of independent prognostic relevance of stress-induced perfusion abnormalities versus mortality, shown by the present study, is not totally surprising. Indeed, optimal medical treatment of the cohort we studied might have hampered the prognostic impact of myocardial perfusion abnormalities, for example, by modifying atherosclerotic plaques stability. Conversely, lower levels of adherence to medical treatment in the study by Shah et al. (statins 50%, ASA 52% and ACE-inhibitors/ARB 44%) might have emphasized the relevance of stress-induced perfusion abnormalities, driving different conclusions about independent prognostic value of SPCMR. Moreover, differences in baseline characteristics between our study and previous studies, for example, higher prevalence of patients with known CAD or MI (86% and 64% in our cohort, respectively), might have influenced predictive value of ischemia versus mortality.
In the present study an indirect confirmation of the low relevance of inducible ischemia in predicting mortality may be considered the lack of independent prognostic value of incident revascularization procedures (49% of patients with positive SPCMR and 24% of the entire cohort underwent revascularization during the follow-up) despite a protective effect emerged at univariate tests. Moreover, none of ischemia related factors we examined, namely, CAD extension, presence of ST segment depression at electrocardiogram, and overall burden of atherosclerotic risk factors, emerged as relevant variables.
The prognostic impact of CMR on a composite endpoint of mortality and relevant morbidities, such as hospitalization for new onset heart failure or ACS and myocardial revascularization procedures unrelated to CMR exam, was confirmed in the present study. CMR introduction into multivariate analysis significantly improved the model fit (p<0.001). Notably, in the final model, LGE and stress-induced perfusion abnormalities were the best predictors of MACE, performing better than LVEF. Large scar at LGE and significant perfusion abnormalities on SPCMR carried a mean 3.3- and 2.1-fold increase of risk of MACE after the correction for all other significant variables. These data confirm the results of previous studies showing that SPCMR is a powerful tool to predict future cardiovascular events [
We intentionally defined relatively loose, “real-world”, entry criteria to enroll a population as representative as possible of referral of a standard outpatient CAD cardiology clinic, bearing in mind that the results of the randomized clinical trials are often difficult to translate into clinical practice due to the stringency of their enrollment criteria. However, loose selection criteria might have hampered the prognostic value of stress-induced ischemia at CMR in specific subsets of patients with stable CAD.
This is a single centre observational study that needs to be confirmed by a randomized multicentre study before drawing definitive conclusions about SPCMR role as a stratifying tool in contemporary population with stable CAD.
Female sex was underrepresented in the study population. Accordingly, some caution must be kept in the inference of the results of the study to female patients.
Patients were enrolled in the study for a relatively long period of time. Although the study protocol, in particular CMR protocol, remained unchanged over time, this might be a source of bias.
Approaching contemporary populations with clinically stable CAD that already receives an optimal evidence based medical treatment: (i) myocardial viability investigation with LGE can be considered a useful tool to further stratify the risk of death in the long term beyond a careful standard clinical and echocardiography assessment; (ii) accurate investigation of myocardial ischemia through SPCMR evaluation does not seem to independently predict mortality; (iii) a comprehensive CMR assessment, including a SPCMR, may be a useful facility to predict morbidity as well as mortality and thus to select subgroups of patients at high risk and high absorption of economical and medical resources.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declared no conflicts of interest.