Left Atrial Function with MRI Enables Prediction of Cardiovascular Events after Myocardial Infarction: Insights from the AIDA STEMI and TATORT NSTEMI Trials.

Background The role of left atrial (LA) performance in acute myocardial infarction (AMI) remains controversial. Cardiac MRI myocardial feature tracking (hereafter, MRI-FT) is a method used to quantify myocardial function that enables reliable assessment of atrial function. Purpose To assess the relationship between LA function assessed with MRI-FT and major adverse cardiovascular events (MACE) after AMI. Materials and Methods This secondary analysis of two prospective multicenter cardiac MRI studies (AIDA STEMI [NCT00712101] and TATORT NSTEMI [NCT01612312]) included 1235 study participants with ST-elevation myocardial infarction (n = 795) or non-ST-elevation myocardial infarction (n = 440) between July 2008 and June 2013. All study participants underwent primary percutaneous coronary intervention. MRI-FT analyses were performed in a core laboratory by researchers blinded to clinical status to determine LA performance using LA reservoir function peak systolic strain (εs), LA conduit strain (εe), and LA booster pump function active strain (εa). The relationship of LA performance to a MACE within 12 months after AMI was evaluated by using Cox proportional hazards models and area under the receiver operating characteristic curve (AUC). Results Study participants with MACE had worse LA performance parameters compared with study participants without MACE (εs = 21.2% vs 16.2%, εe = 8.8% vs 6.9%, εa = 11.8% vs 10%; P < .001 for all). All atrial parameters were strongly associated with MACE (hazard ratio [HR], εs = 0.9, εe = 0.88, εa = 0.89; P < .001 for all). For εs, a cutoff of 18.8% was identified as the only independent atrial parameter with which to predict MACE after accounting for confounders and established prognostic markers in adjusted analysis (HR, 0.95; P = .02). The εs yielded incremental prognostic value above left ventricular ejection fraction, global longitudinal strain, microvascular obstruction, and infarct size (AUC comparisons, P < .04 for all). Conclusion Feature tracking of cardiac MRI to derive left atrial peak reservoir strain provided incremental prognostic value for major adverse cardiovascular events prediction versus established cardiac risk factors after acute myocardial infarction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Myocardial injury and clinical outcome in octogenarians after non-ST-elevation myocardial infarction.

Introduction: The aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI). Methods: This prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1-10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups: <80 years vs. ≥80 years. The clinical endpoint was the 1-year incidence of major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure. Results: Elderly patients ≥80 years accounted for 13.9% of the study population and showed a divergent cardiovascular risk profile compared to the subgroup of patients <80 years. CMR imaging did not reveal significant differences regarding infarct size, microvascular obstruction, left ventricular ejection fraction or multidimensional strain analysis between the study groups. At 1-year follow-up, MACE rate was significantly increased in patients ≥80 years compared to patients aged <80 years (19.7% vs. 9.6%; p = 0.019). In a multiple stepwise logistic regression model, the number of diseased vessels, aldosterone antagonist use and left ventricular global longitudinal strain were identified as independent predictors for MACE in all patients, while there was no independent predictive value of age regarding 1-year clinical outcome. Conclusion: This prospective, multicenter analysis shows that structural and functional myocardial damage is similar in younger and older patients with NSTEMI. Furthermore, in this heterogeneous but also clinically representative cohort with reduced sample size, age was not independently associated with 1-year clinical outcome, despite an increased event rate in patients ≥80 years.

Atrioventricular mechanical coupling and major adverse cardiac events in female patients following acute ST elevation myocardial infarction.

BACKGROUND: Sex-specific outcome data following myocardial infarction (MI) are inconclusive with some evidence suggesting association of female sex and increased major adverse cardiac events (MACE). Since mechanistic principles remain elusive, we aimed to quantify the underlying phenotype using cardiovascular magnetic resonance (CMR) quantitative deformation imaging and tissue characterisation. METHODS: In total, 795 ST-elevation MI patients underwent post-interventional CMR imaging. Feature-tracking (CMR-FT) was performed in a blinded core-laboratory. Left ventricular function was quantified using ejection fraction (LVEF) and global longitudinal/circumferential/radial strains (GLS/GCS/GRS). Left atrial function was assessed by reservoir (εs), conduit (εe) and booster-pump strains (εa). Tissue characterisation included infarct size, microvascular obstruction and area at risk. Primary endpoint was the occurrence of MACE within 1 year. RESULTS: Female sex was associated with increased MACE (HR 1.96, 95% CI 1.13-3.42, p = 0.017) but not independently of baseline confounders (p = 0.526) with women being older, more often diabetic and hypertensive (p < 0.001) and of higher Killip-class (p = 0.010). Tissue characterisation was similar between sexes. Women showed impaired atrial (εs p = 0.011, εe p < 0.001) but increased systolic ventricular mechanics (GLS p = 0.001, LVEF p = 0.048). While atrial and ventricular function predicted MACE in men only LV GLS and GCS were associated with MACE in women irrespective of confounders (GLS p = 0.036, GCS p = 0.04). CONCLUSION: In men ventricular systolic contractility is impaired and volume assessments precisely stratify elevated risks. In contrast, women experience reduced atrial but increased ventricular systolic strain. This may reflect ventricular diastolic failure with systolic compensation, which is independently associated with MACE adding incremental value to sex-specific prognosis evaluation.

Frequency and prognostic impact of right ventricular involvement in acute myocardial infarction.

OBJECTIVE: Right ventricular (RV) involvement complicating myocardial infarction (MI) is thought to impact prognosis, but potent RV markers for risk stratification are lacking. Therefore, the aim of this trial was to assess the frequency and prognostic implications of concomitant structural and functional RV injury in MI. METHODS: Cardiac magnetic resonance (CMR) was performed in 1235 patients with MI (ST-elevation myocardial infarction: n=795; non-STEMI: n=440) 3 days after reperfusion by primary percutaneous coronary intervention. Central core laboratory-masked analyses included structural (oedema representing reversible ischaemia, irreversible infarction, microvascular obstruction (MVO)) and functional (ejection fraction, global longitudinal strain (GLS)) RV alterations. The clinical end point was the 12-month rate of major adverse cardiac events (MACE). RESULTS: RV ischaemia and infarction were observed in 19.6% and 12.1% of patients, respectively, suggesting complete myocardial salvage in one-third of patients. RV ischaemia was associated with a significantly increased risk of MACE (10.1% vs 6.2%; p=0.035), while patients with RV infarction showed only numerically increased event rates (p=0.075). RV MVO was observed in 2.4% and not linked to outcome (p=0.894). Stratification according to median RV GLS (10.2% vs 3.8%; p<0.001) but not RV ejection fraction (p=0.175) resulted in elevated MACE rates. Multivariable analysis including clinical and left ventricular MI characteristics identified RV GLS as an independent predictor of outcome (HR 1.05, 95% CI 1.00 to 1.09; p=0.034) in addition to age (p=0.001), Killip class (p=0.020) and left ventricular GLS (p=0.001), while RV ischaemia was not independently associated with outcome. CONCLUSIONS: RV GLS is a predictor of postinfarction adverse events over and above established risk factors, while structural RV involvement was not independently associated with outcome.

Cardiac Magnetic Resonance Myocardial Feature Tracking for Optimized Risk Assessment After Acute Myocardial Infarction in Patients With Type 2 Diabetes.

Type 2 diabetes predicts outcome following acute myocardial infarction (AMI). Since underlying mechanics are incompletely understood, we investigated left ventricular (LV) and left atrial (LA) pathophysiological changes and their prognostic implications using cardiovascular magnetic resonance (CMR). Consecutive patients (N = 1,147; n = 265 with diabetes, n = 882 without diabetes) underwent CMR 3 days after AMI. Analyses included LV ejection fraction (LVEF); global longitudinal strain (GLS) and circumferential and radial strains; LA reservoir, conduit, and booster pump strains; and infarct size, edema, and microvascular obstruction. Predefined end points were major adverse cardiovascular events (MACE) within 12 months. Patients with diabetes had impaired LA reservoir (19.8% vs. 21.2%, P < 0.01) and conduit (7.6% vs. 9.0%, P < 0.01) strains but not ventricular function or myocardial damage. They were at higher risk of MACE than patients without diabetes (10.2% vs. 5.8%, P < 0.01), with most MACE occurring in patients with LVEF ≥35%. While LVEF (P = 0.045) and atrial reservoir strain (P = 0.024) were independent predictors of MACE in patients without diabetes, GLS was in patients with diabetes (P = 0.010). Considering patients with diabetes and LVEF ≥35% (n = 237), GLS and LA reservoir strain below median were significantly associated with MACE. In conclusion, in patients with diabetes, LA and LV longitudinal strain permit optimized risk assessment early after reperfused AMI with incremental prognostic value over and above that of LVEF.

Impact of Right Atrial Physiology on Heart Failure and Adverse Events after Myocardial Infarction.

Background: Right ventricular (RV) function is a known predictor of adverse events in heart failure and following acute myocardial infarction (AMI). While right atrial (RA) involvement is well characterized in pulmonary arterial hypertension, its relative contributions to adverse events following AMI especially in patients with heart failure and congestion need further evaluation. Methods: In this cardiovascular magnetic resonance (CMR)-substudy of AIDA STEMI and TATORT NSTEMI, 1235 AMI patients underwent CMR after primary percutaneous coronary intervention (PCI) in 15 centers across Germany (n = 795 with ST-elevation myocardial infarction and 440 with non-ST-elevation MI). Right atrial (RA) performance was evaluated using CMR myocardial feature tracking (CMR-FT) for the assessment of RA reservoir (total strain εs), conduit (passive strain εe), booster pump function (active strain εa), and associated strain rates (SR) in a blinded core-laboratory. The primary endpoint was the occurrence of major adverse cardiac events (MACE) 12 months post AMI. Results: RA reservoir (εs p = 0.061, SRs p = 0.049) and conduit functions (εe p = 0.006, SRe p = 0.030) were impaired in patients with MACE as opposed to RA booster pump (εa p = 0.579, SRa p = 0.118) and RA volume index (p = 0.866). RA conduit function was associated with the clinical onset of heart failure and MACE independently of RV systolic function and atrial fibrillation (AF) (multivariable analysis hazard ratio 0.95, 95% confidence interval 0.92 to 0.99, p = 0.009), while RV systolic function and AF were not independent prognosticators. Furthermore, RA conduit strain identified low- and high-risk groups within patients with reduced RV systolic function (p = 0.019 on log rank testing). Conclusions: RA impairment is a distinct feature and independent risk factor in patients following AMI and can be easily assessed using CMR-FT-derived quantification of RA strain.

Culprit vessel-related myocardial mechanics and prognostic implications following acute myocardial infarction.

BACKGROUND: Prognosis in acute myocardial infarction (AMI) depends on the amount of infarct-related artery (IRA)-subtended myocardium and associated damage but has not been described in great detail. Consequently, we sought to describe IRA-associated pathophysiological consequences using cardiac magnetic resonance (CMR). METHODS: 1235 AMI patients (n = 795 ST-elevation (STEMI) and 440 non-STEMI) underwent CMR following percutaneous coronary intervention. Blinded core-laboratory data were compared according to left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA) regarding major adverse clinical events (MACE) within 12 months. Left ventricular (LV) global longitudinal/circumferential/radial (GLS/GCS/GRS) as well as left atrial (LA) total (εs), passive (εe) and active (εa) strains were determined using CMR-feature tracking. Tissue characterisation included infarct size (IS) and microvascular obstruction. RESULTS: LAD and LCx were associated with higher mortality compared to RCA lesions (4.6% and 4.4% vs 1.6%). LAD lesions showed largest IS (16.8%), largest ventricular [LV ejection fraction (EF) 47.4%, GLS - 13.2%, GCS - 20.8%] and atrial (εs 20.2%) impairment. There was less impairment in LCx (IS 11.8%, LVEF 50.8%, GLS - 17.4%, GCS - 25.0%, εs 20.7%) followed by RCA lesions (IS 11.3%, LVEF 50.8%, GLS - 19.1%, GCS - 26.6%, εs 21.7%). In AUC analyses, εs (LAD, RCA) and GLS (LCx) best predicted MACE (AUC > 0.69). Multivariate analyses identified εs (p = 0.017) in LAD and GLS (p = 0.034) in LCx infarcts as independent predictors of MACE. CONCLUSIONS: CMR allows IRA-specific phenotyping and characterisation of morphologic and functional changes. These alterations carry infarct-specific prognostic implications, and may represent novel diagnostic and therapeutic targets following AMI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00712101 and NCT01612312.

Fast manual long-axis strain assessment provides optimized cardiovascular event prediction following myocardial infarction.

AIMS: Cardiovascular magnetic resonance feature tracking (CMR-FT) global longitudinal strain (GLS) provides incremental prognostic value following acute myocardial infarction (AMI) but requires substantial post-processing. Alternatively, manual global long-axis strain (LAS) can be easily assessed from standard steady state free precession images. We aimed to define the prognostic value of LAS in a large multicentre study in patients following AMI. METHODS AND RESULTS: A total of 1235 patients with myocardial infarction [n = 795 with ST-elevation myocardial infarction (STEMI) and 440 with non-ST-elevation myocardial infarction (NSTEMI)] underwent cardiovascular magnetic resonance imaging after primary percutaneous coronary intervention in eight centres across Germany. Assessment of LAS was performed in a blinded core-laboratory measuring the systolic shortening between the epicardial apical border and the middle of a line connecting the origins of the mitral leaflets. Primary clinical endpoint was the occurrence of major adverse clinical events (MACE) including death, reinfarction, and congestive heart failure within 1 year after AMI. During 1-year follow-up, 76 patients suffered from MACE. Impaired LAS was associated with higher MACE occurrence both in STEMI (P < 0.001) and NSTEMI (P = 0.001) patients. Association of LAS remained significant (P = 0.017) after correction for univariate significant parameters for MACE prediction. C-statistics revealed incremental value of additional LAS assessment for optimized event prediction compared with left ventricular ejection fraction (MACE P = 0.044; mortality P = 0.013) and a combination of established clinical and imaging parameters (MACE P = 0.084; mortality P = 0.027), but not CMR-FT GLS (MACE P = 0.075; mortality P = 0.380). CONCLUSION: LAS provides software independent, widely available, easy and fast approximation of longitudinal left ventricular shortening early after reperfused AMI with incremental prognostic value beyond established risk stratification parameters. CLINICAL TRIALS.GOV: NCT00712101 and NCT01612312.

Cardiac Magnetic Resonance Left Ventricular Mechanical Uniformity Alterations for Risk Assessment After Acute Myocardial Infarction.

Background Despite limitations as a stand-alone parameter, left ventricular (LV) ejection fraction is the preferred measure of myocardial function and marker for postinfarction risk stratification. LV myocardial uniformity alterations may provide superior prognostic information after acute myocardial infarction, which was the subject of this study. Methods and Results Consecutive patients with acute myocardial infarction (n=1082; median age: 63 years; 75% male) undergoing cardiac magnetic resonance at a median of 3 days after infarction were included in this multicenter observational study. Circumferential and radial uniformity ratio estimates were derived from cardiac magnetic resonance feature tracking as markers of mechanical uniformity alterations (values between 0 and 1 with 1 reflecting perfect uniformity). The clinical end point was the 12-month rate of major adverse cardiac events, consisting of all-cause death, reinfarction, and new congestive heart failure. Patients with major adverse cardiac events (n=73) had significantly impaired circumferential uniformity ratio estimates (0.76 [interquartile range: 0.67-0.86] versus 0.84 [interquartile range: 0.76-0.89]; P<0.001) and radial uniformity ratio estimates (0.69 [interquartile range: 0.60-0.79] versus 0.76 [interquartile range: 0.67-0.83]; P<0.001) compared with patients without events. Although uniformity estimates did not provide independent prognostic information in the overall cohort, a circumferential uniformity ratio estimate below the median of 0.84 emerged as an independent predictor of outcome in postinfarction patients with LV ejection fraction >35% (n=959), even after adjustment for established risk factors (hazard ratio: 1.99; 95% CI, 1.06-3.74; P=0.033 in multivariable Cox regression analysis). In contrast, LV ejection fraction was not associated with adverse events in this subgroup of patients with acute myocardial infarction. Conclusions Cardiac magnetic resonance-derived estimates of mechanical uniformity alterations are novel markers for risk assessment after acute myocardial infarction, and the circumferential uniformity ratio estimate provides independent prognostic information for patients with preserved or only moderately reduced LV ejection fraction.

Cardiac Magnetic Resonance Myocardial Feature Tracking for Optimized Prediction of Cardiovascular Events Following Myocardial Infarction.

OBJECTIVES: The aims of the study were to assess the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in a large multicenter study and to evaluate the most potent CMR-FT predictor of hard clinical events following myocardial infarction (MI). BACKGROUND: CMR-FT is a new method that allows accurate assessment of global and regional circumferential, radial, and longitudinal myocardial strain. The prognostic value of CMR-FT in patients with reperfused MI is unknown. METHODS: The study included 1,235 MI patients (n = 795 with ST-segment elevation MI and 440 with non-ST-elevation MI) at 15 centers. All patients were reperfused by primary percutaneous coronary intervention. Central core laboratory-masked analyses were performed to determine left ventricular (LV) circumferential, radial, and longitudinal strain. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events within 12 months after infarction. RESULTS: Patients with cardiovascular events had significantly impaired CMR-FT strain values (p < 0.001 for all). Global longitudinal strain was identified as the strongest CMR-FT parameter of future cardiovascular events and emerged as an independent predictor of poor prognosis following MI even after adjustment for established prognostic markers. Global longitudinal strain provided an incremental prognostic value for all-cause mortality above LV ejection fraction (c-index increase from 0.65 to 0.73; p = 0.04) and infarct size (c-index increase from 0.60 to 0.78; p = 0.002). CONCLUSIONS: CMR-FT is a superior measure of LV function and performance early after reperfused MI with incremental prognostic value for mortality over and above LV ejection fraction and infarct size. (Abciximab i.v. Versus i.c. in ST-segment elevation Myocardial Infarction [AIDA STEMI]; NCT00712101; Thrombus Aspiration in ThrOmbus Containing culpRIT Lesions in Non-ST-Elevation Myocardial Infarction [TATORT-NSTEMI]; NCT01612312).