Empagliflozin to prevent progressive adverse remodelling after myocardial infarction (EMPRESS-MI): rationale and design.

AIMS: Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. METHODS AND RESULTS: EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10 mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24 weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers. CONCLUSIONS: EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI.

Clinical Outcomes Associated With Various Microvascular Injury Patterns Identified by CMR After STEMI.

BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.

Dapagliflozin in patients with heart failure and previous myocardial infarction: A participant-level pooled analysis of DAPA-HF and DELIVER.

AIMS: Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood. METHODS AND RESULTS: The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular death or worsening HF. Of the total of 11 007 patients, 3731 (34%) had a previous MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02-1.24). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83, 95% CI 0.72-0.96) and without previous MI (HR 0.76, 95% CI 0.68-0.85; pinteraction = 0.36), with consistent benefits on key secondary outcomes as well. Serious adverse events did not occur more frequently with dapagliflozin, irrespective of previous MI. CONCLUSION: History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the LVEF spectrum, even among those with preserved ejection fraction. Dapagliflozin consistently and safely reduces the risk of cardiovascular death or worsening HF, regardless of previous MI.

Infarct severity and outcomes in ST-elevation myocardial infarction patients without standard modifiable risk factors - A multicenter cardiac magnetic resonance study.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs) are well-established players in the pathogenesis of ST-elevation myocardial infarction (STEMI). However, in a significant proportion of STEMI patients, no SMuRFs can be identified, and the outcomes of this subgroup are not well described. OBJECTIVES: To assess the infarct characteristics at myocardial-tissue level and subsequent clinical outcomes in SMuRF-less STEMIs. METHODS: This multicenter, individual patient-data analysis included 2012 STEMI patients enrolled in four cardiac magnetic resonance (CMR) imaging studies conducted in Austria, Germany, Scotland, and the Netherlands. Unstable patients at time of CMR (e.g. cardiogenic shock/after cardiac arrest) were excluded. SMuRF-less was defined as absence of hypertension, smoking, hypercholesterolemia, and diabetes mellitus. All patients underwent CMR 3(interquartile range [IQR]:2-4) days after infarction to assess left ventricular (LV) volumes and ejection fraction, infarct size and microvascular obstruction (MVO). Clinical endpoints were defined as major adverse cardiovascular events (MACE), including all-cause mortality, re-infarction and heart failure. RESULTS: No SMuRF was identified in 185 patients (9%). These SMuRF-less patients were older, more often male, had lower TIMI risk score and pre-interventional TIMI flow, and less frequently multivessel-disease. SMuRF-less patients did not show significant differences in CMR markers compared to patients with SMuRFs (all p > 0.10). During a median follow-up of 12 (IQR:12-27) months, 199 patients (10%) experienced a MACE. No significant difference in MACE rates was observed between SMuRF-less patients and patients with SMuRFs (8vs.10%, p = 0.39). CONCLUSIONS: In this large individual patient-data pooled analysis of low-risk STEMI patients, infarct characteristics and clinical outcomes were not different according to SMuRF status.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data.

BACKGROUND: Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. OBJECTIVES: The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. METHODS: In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. RESULTS: In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. CONCLUSIONS: In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: This study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure. BACKGROUND: A cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score. RESULTS: There were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score. CONCLUSIONS: This noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

Redefining Adverse and Reverse Left Ventricular Remodeling by Cardiovascular Magnetic Resonance Following ST-Segment-Elevation Myocardial Infarction and Their Implications on Long-Term Prognosis.

BACKGROUND: Cut off values for change in left ventricular end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) by cardiovascular magnetic resonance following ST-segment-elevation myocardial infarction have recently been proposed and 4 patterns of LV remodeling were described. We aimed to assess their long-term prognostic significance. METHODS: A prospective cohort of unselected patients with ST-segment-elevation myocardial infarction with paired acute and 6-month cardiovascular magnetic resonance, with the 5-year composite end point of all-cause death and hospitalization for heart failure was included. The prognosis of the following groups (group 1: reverse LV remodeling [≥12% decrease in LVESV]; group 2: no LV remodeling [changes in LVEDV and LVESV <12%]; group 3: adverse LV remodeling with compensation [≥12% increase in LVEDV only]; and group 4: adverse LV remodeling [≥12% increase in both LVESV and LVEDV]) was compared. RESULTS: Two hundred eighty-five patients were included with a median follow-up was 5.8 years. The composite end point occurred in 9.5% in group 1, 12.3% in group 2, 7.1% in group 3, and 24.2% in group 4. Group 4 had significantly higher cumulative event rates of the composite end point (log-rank test, P=0.03) with the other 3 groups showing similar cumulative event rates (log-rank test, P=0.51). Cox proportional hazard for group 2 (hazard ratio, 1.3 [95% CI, 0.6-3.1], P=0.53) and group 3 (hazard ratio, 0.6 [95% CI, 0.2-2.3], P=0.49) were not significantly different but was significantly higher in group 4 (hazard ratio, 3.0 [95% CI, 1.2-7.1], P=0.015) when compared with group 1. CONCLUSIONS: Patients with ST-segment-elevation myocardial infarction developing adverse LV remodeling at 6 months, defined as ≥12% increase in both LVESV and LVEDV by cardiovascular magnetic resonance, was associated with worse long-term clinical outcomes than those with adverse LV remodeling with compensation, reverse LV remodeling, and no LV remodeling, with the latter 3 groups having similar outcomes in a cohort of stable reperfused patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Creating three dimensional models of the right ventricular outflow tract: influence of contrast, sequence, operator, and threshold.

The use of 3D printed models of the right ventricular outflow tract (RVOT) for surgical and interventional planning is growing and often requires image segmentation of cardiac magnetic resonance (CMR) images. Segmentation results may vary based on contrast, image sequence, signal threshold chosen by the operator, and manual post-processing. The purpose of this study was to determine potential biases and post-processing errors in image segmentation to enable informed decisions. Models of the RVOT and pulmonary arteries from twelve patients who had contrast enhanced CMR angiography with gadopentetate dimeglumine (GPD), gadofosveset trisodium (GFT), and a post-GFT inversion-recovery (IR) whole heart sequence were segmented, trimmed, and aligned by three operators. Geometric agreement and minimal RVOT diameters were compared between sequences and operators. To determine the contribution of threshold, interoperator variability was compared between models created by the same two operators using the same versus different thresholds. Geometric agreement by Dice between objects was high (intraoperator: 0.89-0.95; interoperator: 0.95-0.97), without differences between sequences. Minimal RVOT diameters differed on average by - 1.9 to - 1.3 mm (intraoperator) and by 0.4 to 1.4 mm (interoperator). The contribution of threshold to interoperator geometric agreement was not significant (same threshold: 0.96 ± 0.06, different threshold: 0.93 ± 0.05; p = 0.181), but minimal RVOT diameters were more variable with different versus constant thresholds (- 9.12% vs. 2.42%; p < 0.05). Thresholding does not significantly change interoperator variability for geometric agreement, but does for minimal RVOT diameter. Minimal RVOT diameters showed clinically relevant variation within and between operators.

Sex-based associations with microvascular injury and outcomes after ST-segment elevation myocardial infarction.

Objectives: We aimed to assess for sex differences in invasive parameters of acute microvascular reperfusion injury and infarct characteristics on cardiac MRI after ST-segment elevation myocardial infarction (STEMI). Methods: Patients with STEMI undergoing emergency percutaneous coronary intervention (PCI) were prospectively enrolled. Index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery post-PCI. Contrast-enhanced MRI was used to assess infarct characteristics, microvascular obstruction and myocardial haemorrhage, 2 days and 6 months post-STEMI. Prespecified outcomes were as follows: (i) all-cause death/first heart failure hospitalisation and (ii) cardiac death/non-fatal myocardial infarction/urgent coronary revascularisation (major adverse cardiovascular event, MACE) during 5- year median follow-up. Results: In 324 patients with STEMI (87 women, mean age: 61 ± 12.19 years; 237 men, mean age: 59 ± 11.17 years), women had anterior STEMI less often, fewer prescriptions of beta-blockers at discharge and higher baseline N-terminal pro-B-type natriuretic peptide levels (all p < 0.05). Following emergency PCI, fewer women than men had Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grades ≤ 1 (20% vs 32%, p = 0.027) and women had lower corrected TIMI frame counts (12.94 vs 17.65, p = 0.003). However, IMR, CFR, microvascular obstruction, myocardial haemorrhage, infarct size, myocardial salvage index, left ventricular remodelling and ejection fraction did not differ significantly between sexes. Female sex was not associated with MACE or all-cause death/first heart failure hospitalisation. Conclusion: There were no sex differences in microvascular pathology in patients with acute STEMI. Women had less anterior infarcts than men, and beta-blocker therapy at discharge was prescribed less often in women. Trial registration number: NCT02072850.

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights.

OBJECTIVES: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). BACKGROUND: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. METHODS: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. RESULTS: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). CONCLUSIONS: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Circumferential Strain Predicts Major Adverse Cardiovascular Events Following an Acute ST-Segment-Elevation Myocardial Infarction.

Purpose To investigate the prognostic value of circumferential left ventricular (LV) strain measured by using cardiac MRI for prediction of major adverse cardiac events (MACE) following an acute ST-segment-elevation myocardial infarction (STEMI). Materials and Methods Participants with acute STEMI were prospectively enrolled from May 11, 2011, to November 22, 2012. Cardiac MRI was performed at 1.5 T during the index hospitalization. Displacement encoding with stimulated echoes (DENSE) and feature tracking of cine cardiac MRI was used to assess circumferential LV strain. MACE that occurred after discharge were independently assessed by cardiologists blinded to the baseline observations. Results A total of 259 participants (mean age, 58 years ± 11 [standard deviation]; 198 men [mean age, 58 years ± 11] and 61 women [mean age, 58 years ± 12]) underwent cardiac MRI 2.2 days ± 1.9 after STEMI. Average infarct size was 18% ± 13 of LV mass and circumferential strain was -13% ± 3 (DENSE method) and -24% ± 7 (feature- tracking method). Fifty-one percent (131 of 259 participants) had presence of microvascular obstruction. During a median follow-up period of 4 years, 8% (21 of 259) experienced MACE. Area under the curve (AUC) for DENSE was different from that of feature tracking (AUC, 0.76 vs 0.62; P = .03). AUC for DENSE was similar to that of initial infarct size (P = .06) and extent of microvascular obstruction (P = .08). DENSE-derived strain provided incremental prognostic benefit over infarct size for prediction of MACE (hazard ratio, 1.3; P < .01). Conclusion Circumferential strain has independent prognostic importance in study participants with acute ST-segment-elevation myocardial infarction. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Kramer in this issue.

Coronary Thermodilution Waveforms After Acute Reperfused ST-Segment-Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognosis.

Background Invasive measures of microvascular resistance in the culprit coronary artery have potential for risk stratification in acute ST-segment-elevation myocardial infarction. We aimed to investigate the pathological and prognostic significance of coronary thermodilution waveforms using a diagnostic guidewire. Methods and Results Coronary thermodilution was measured at the end of percutaneous coronary intervention, (PCI) and contrast-enhanced cardiac magnetic resonance imaging (MRI) was intended on day 2 and 6 months later to assess left ventricular (LV) function and pathology. All-cause death or first heart failure hospitalization was a pre-specified outcome (median follow-up duration 1469 days). Thermodilution recordings underwent core laboratory assessment. A total of 278 patients with acute ST-segment elevation myocardial infarction EMI (72% male, 59±11 years) had coronary thermodilution measurements classified as narrow unimodal (n=143 [51%]), wide unimodal (n=100 [36%]), or bimodal (n=35 [13%]). Microvascular obstruction and myocardial hemorrhage were associated with the thermodilution waveform pattern ( P=0.007 and 0.011, respectively), and both pathologies were more prevalent in patients with a bimodal morphology. On multivariate analysis with baseline characteristics, thermodilution waveform status was a multivariable associate of microvascular obstruction (odds ratio [95% confidence interval]=5.29 [1.73, 16.22];, P=0.004) and myocardial hemorrhage (3.45 [1.16, 10.26]; P=0.026), but the relationship was not significant when index of microvascular resistance (IMR) >40 or change in index of microvascular resistance (5 per unit) was included. However, a bimodal thermodilution waveform was independently associated with all-cause death and hospitalization for heart failure (odds ratio [95% confidence interval]=2.70 [1.10, 6.63]; P=0.031), independent of index of microvascular resistance>40, ST-segment resolution, and TIMI (Thrombolysis in Myocardial Infarction) Myocardial Perfusion Grade. Conclusions The thermodilution waveform in the culprit coronary artery is a biomarker of prognosis and may be useful for risk stratification immediately after reperfusion therapy.

Hypertension, Microvascular Pathology, and Prognosis After an Acute Myocardial Infarction.

The rationale for our study was to investigate the pathophysiology of microvascular injury in patients with acute ST-segment-elevation myocardial infarction in relation to a history of hypertension. We undertook a cohort study using invasive and noninvasive measures of microvascular injury, cardiac magnetic resonance imaging at 2 days and 6 months, and assessed health outcomes in the longer term. Three hundred twenty-four patients with acute myocardial infarction (mean age, 59 [12] years; blood pressure, 135 [25] / 79 [14] mm Hg; 237 [73%] male, 105 [32%] with antecedent hypertension) were prospectively enrolled during emergency percutaneous coronary intervention. Compared with patients without antecedent hypertension, patients with hypertension were older (63 [12] years versus 57 [11] years; P<0.001) and a lower proportion were cigarette smokers (52 [50%] versus 144 [66%]; P=0.007). Coronary blood flow, microvascular resistance within the culprit artery, infarct pathologies, inflammation (C-reactive protein and interleukin-6) were not associated with hypertension. Compared with patients without antecedent hypertension, patients with hypertension had less improvement in left ventricular ejection fraction at 6 months from baseline (5.3 [8.2]% versus 7.4 [7.6]%; P=0.040). Antecedent hypertension was a multivariable associate of incident myocardial hemorrhage 2-day post-MI (1.81 [0.98-3.34]; P=0.059) and all-cause death or heart failure (n=47 events, n=24 with hypertension; 2.53 [1.28-4.98]; P=0.007) postdischarge (median follow-up 4 years). Severe progressive microvascular injury is implicated in the pathophysiology and prognosis of patients with a history of hypertension and acute myocardial infarction. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02072850.

Persistent Iron Within the Infarct Core After ST-Segment Elevation Myocardial Infarction: Implications for Left Ventricular Remodeling and Health Outcomes.

OBJECTIVES: This study sought to determine the incidence and prognostic significance of persistent iron in patients post-ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The clinical significance of persistent iron within the infarct core after STEMI complicated by acute myocardial hemorrhage is poorly understood. METHODS: Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction]). Cardiac magnetic resonance imaging including T2* (observed time constant for the decay of transverse magnetization seen with gradient-echo sequences) mapping was performed at 2 days and 6 months post-STEMI. Myocardial hemorrhage or iron was defined as a hypointense infarct core with T2* signal <20 ms. RESULTS: A total of 203 patients (age 57 ± 11 years, n = 158 [78%] male) had evaluable T2* maps at 2 days and 6 months post-STEMI; 74 (36%) patients had myocardial hemorrhage at baseline, and 44 (59%) of these patients had persistent iron at 6 months. Clinical associates of persistent iron included heart rate (p = 0.009), the absence of a history of hypertension (p = 0.017), and infarct size (p = 0.028). The presence of persistent iron was associated with worsening left ventricular (LV) end-diastolic volume (regression coefficient: 21.10; 95% confidence interval [CI]: 10.92 to 31.27; p < 0.001) and worsening LV ejection fraction (regression coefficient: -6.47; 95% CI: -9.22 to -3.72; p < 0.001). Persistent iron was associated with the subsequent occurrence of all-cause death or heart failure (hazard ratio: 3.91; 95% CI: 1.37 to 11.14; p = 0.011) and major adverse cardiac events (hazard ratio: 3.24; 95% CI: 1.09 to 9.64; p = 0.035) (median follow-up duration 1,457 days [range 233 to 1,734 days]). CONCLUSIONS: Persistent iron at 6 months post-STEMI is associated with worse LV and longer-term health outcomes. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

Persistence of Infarct Zone T2 Hyperintensity at 6 Months After Acute ST-Segment-Elevation Myocardial Infarction: Incidence, Pathophysiology, and Prognostic Implications.

BACKGROUND: The incidence and clinical significance of persistent T2 hyperintensity after acute ST-segment-elevation myocardial infarction (STEMI) is uncertain. METHODS AND RESULTS: Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI: NCT02072850). Two hundred eighty-three STEMI patients (mean age, 59±12 years; 75% male) had cardiac magnetic resonance with T2 mapping performed at 2 days and 6 months post-STEMI. Persisting T2 hyperintensity was defined as infarct T2 >2 SDs from remote T2 at 6 months. Infarct zone T2 was higher than remote zone T2 at 2 days (66.3±6.1 versus 49.7±2.1 ms; P<0.001) and 6 months (56.8±4.5 versus 49.7±2.3 ms; P<0.001). Remote zone T2 did not change over time (mean change, 0.0±2.7 ms; P=0.837), whereas infarct zone T2 decreased (-9.5±6.4 ms; P<0.001). At 6 months, T2 hyperintensity persisted in 189 (67%) patients, who were more likely to have Thrombus in Myocardial Infarction flow 0 or 1 in the culprit artery (P=0.020), incomplete ST-segment resolution (P=0.037), and higher troponin (P=0.024). Persistent T2 hyperintensity was associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration (0.57 on a log scale [0.42-0.72]; P=0.004) and the likelihood of adverse left ventricular remodeling (>20% change in left ventricular end-diastolic volume; 21.91 [2.75-174.29]; P=0.004). Persistent T2 hyperintensity was associated with all-cause death and heart failure, but the result was not significant (P=0.051). ΔT2 was associated with all-cause death and heart failure (P=0.004) and major adverse cardiac events (P=0.013). CONCLUSIONS: Persistent T2 hyperintensity occurs in two thirds of STEMI patients. Persistent T2 hyperintensity was associated with the initial STEMI severity, adverse remodeling, and long-term health outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Diagnostic Accuracy of 3.0-T Magnetic Resonance T1 and T2 Mapping and T2-Weighted Dark-Blood Imaging for the Infarct-Related Coronary Artery in Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Patients with recent non-ST-segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. METHODS AND RESULTS: We prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2-weighted short tau inversion recovery [T2W-STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non-ST-segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0-T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct-related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W-STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct-related artery were similar (P=0.125), and both were superior to T2W-STIR (P<0.001). The extent of myocardial injury (percentage of left ventricular volume) estimated with T1 (15.8±10.6%) and T2 maps (16.0±11.8%) was similar (P=0.838) and moderately well correlated (r=0.82, P<0.001). Mean extent of acute injury estimated with T2W-STIR (7.8±11.6%) was lower than that estimated with T1 (P<0.001) or T2 maps (P<0.001). CONCLUSIONS: In patients with non-ST-segment elevation myocardial infarction, T1 and T2 magnetic resonance imaging mapping have higher diagnostic performance than T2W-STIR for identifying the infarct-related artery. Compared with conventional STIR, T1 and T2 maps have superior value to inform diagnosis and revascularization planning in non-ST-segment elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.