Cardiac Magnetic Resonance Imaging Versus Computed Tomography to Guide Transcatheter Aortic Valve Replacement: A Randomized, Open-Label, Noninferiority Trial.

BACKGROUND: Computed tomography (CT) is recommended for guiding transcatheter aortic valve replacement (TAVR). However, a sizable proportion of TAVR candidates have chronic kidney disease, in whom the use of iodinated contrast media is a limitation. Cardiac magnetic resonance imaging (CMR) is a promising alternative, but randomized data comparing the effectiveness of CMR-guided versus CT-guided TAVR are lacking. METHODS: An investigator-initiated, prospective, randomized, open-label, noninferiority trial was conducted at 2 Austrian heart centers. Patients evaluated for TAVR according to the inclusion criteria (severe symptomatic aortic stenosis) and exclusion criteria (contraindication to CMR, CT, or TAVR, a life expectancy <1 year, or chronic kidney disease level 4 or 5) were randomized (1:1) to undergo CMR or CT guiding. The primary outcome was defined according to the Valve Academic Research Consortium-2 definition of implantation success at discharge, including absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance. Noninferiority was assessed using a hybrid modified intention-to-treat/per-protocol approach on the basis of an absolute risk difference margin of 9%. RESULTS: Between September 11, 2017, and December 16, 2022, 380 candidates for TAVR were randomized to CMR-guided (191 patients) or CT-guided (189 patients) TAVR planning. Of these, 138 patients (72.3%) in the CMR-guided group and 129 patients (68.3%) in the CT-guided group eventually underwent TAVR (modified intention-to-treat cohort). Of these 267, 19 patients had protocol deviations, resulting in a per-protocol cohort of 248 patients (121 CMR-guided, 127 CT-guided). In the modified intention-to-treat cohort, implantation success was achieved in 129 patients (93.5%) in the CMR group and in 117 patients (90.7%) in the CT group (between-group difference, 2.8% [90% CI, -2.7% to 8.2%]; P<0.01 for noninferiority). In the per-protocol cohort (n=248), the between-group difference was 2.0% (90% CI, -3.8% to 7.8%; P<0.01 for noninferiority). CONCLUSIONS: CMR-guided TAVR was noninferior to CT-guided TAVR in terms of device implantation success. CMR can therefore be considered as an alternative for TAVR planning. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03831087.

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. RESULTS: Intramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60-23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16). CONCLUSIONS: In STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications.

Prognostic value of pulmonary transit time by cardiac magnetic resonance imaging in ST-elevation myocardial infarction.

OBJECTIVES: To investigate the prognostic value of pulmonary transit time (pTT) determined by cardiac magnetic resonance (CMR) after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: Comprehensive CMR examinations were performed in 207 patients 3 days and 4 months after reperfused STEMI. Functional parameters and infarct characteristics were assessed. PTT was defined as the interval between peaks of gadolinium contrast time-intensity curves in the right and left ventricles in first-pass perfusion imaging. Cox regression models were calculated to assess the association between pTT and the occurrence of major adverse cardiac events (MACE), defined as a composite of death, re-infarction, and congestive heart failure. RESULTS: PTT was 8.6 s at baseline and 7.8 s at the 4-month CMR. In Cox regression, baseline pTT (hazard ratio [HR]: 1.58; 95% CI: 1.12 to 2.22; p = 0.009) remained significantly associated with MACE occurrence after adjustment for left ventricular ejection fraction (LVEF) and cardiac index. The association of pTT and MACE remained significant also after adjusting for infarct size and microvascular obstruction size. In Kaplan-Meier analysis, pTT ≥ 9.6 s was associated with MACE (p < 0.001). Addition of pTT to LVEF resulted in a categorical net reclassification improvement of 0.73 (95% CI: 0.27 to 1.20; p = 0.002) and integrated discrimination improvement of 0.07 (95% CI: 0.02 to 0.13; p = 0.007). CONCLUSIONS: After reperfused STEMI, CMR-derived pTT was associated with hard clinical events with prognostic information independent of and incremental to infarct size and LV systolic function. KEY POINTS: • Pulmonary transit time is the duration it takes the heart to pump blood from the right chambers across lung vessels to the left chambers. • This prospective single-centre study showed inferior outcome in patients with prolonged pulmonary transit time after myocardial infarction. • Pulmonary transit time assessed by magnetic resonance imaging added incremental information to established prognostic markers.

Impact of COVID-19 pandemic restrictions on ST-elevation myocardial infarction: a cardiac magnetic resonance imaging study.

AIMS: The severity of myocardial tissue damage following ST-elevation myocardial infarction (STEMI) strongly determines short- and long-term prognosis. This study explored the impact of the coronavirus disease 2019 (COVID-19) pandemic and associated public health restrictions on infarct severity. METHODS AND RESULTS: STEMI patients treated with primary percutaneous coronary intervention (PCI) and included in the prospective Magnetic Resonance Imaging in Acute ST-Elevation Myocardial Infarction (MARINA-STEMI) cohort study from 2015- 2020 (n = 474) were categorized according to (i) timeframes with and without major public health restrictions in 2020, and (ii) timeframes of major public health restrictions during 2020 and during the corresponding timeframes between 2015-2019. Myocardial damage was evaluated by cardiac magnetic resonance imaging. During major public health restrictions in 2020 (n = 48), there was an increase in infarct size (22 [IQR 12-29] vs. 14 [IQR 6-23]%, P < 0.01), a higher frequency (77% vs. 52%, P < 0.01) and larger extent of microvascular obstruction (1.5 [IQR 0.1-11.4] vs. 0.2 [IQR 0.0-2.6]%, P < 0.01) and a higher rate of intramyocardial haemorrhage (56% vs. 34%, P = 0.02) as compared to the phases without major restrictions in 2020 (n = 101). These findings were confirmed in adjusted analysis and were consistent when comparing patients admitted in 2020 versus patients admitted in the "pre-pandemic" era (2015-2019). Patient characteristics were comparable between groups, except for a significantly longer total ischemia time (P < 0.01) and higher frequency of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow 0 during times of major restrictions (P = 0.03). CONCLUSION: This study provides novel mechanistic insights demonstrating a significant increase in myocardial damage in STEMI patients admitted during the COVID-19 pandemic with a temporal relation to major public health restrictions.

A novel approach to determine aortic valve area with phase-contrast cardiovascular magnetic resonance.

BACKGROUND: Transthoracic echocardiography (TTE) is the diagnostic routine standard for assessing aortic stenosis (AS). However, its inaccuracies in determining stroke volume (SV) and aortic valve area (AVA) call for a more precise and dependable method. Phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) is a promising tool to push these boundaries. Thus, the aim of this study was to validate a novel approach based on PC-CMR against the gold-standard of invasive determination of AVA in AS compared to TTE. METHODS: A total of 50 patients with moderate or severe AS underwent TTE, cardiac catheterization and CMR. AVA via PC-CMR was determined by plotting momentary flow across the valve against flow-velocity. SV by CMR was measured directly via PC-CMR and volumetrically using cine-images. Invasive SV and AVA were determined via Fick-principle and Gorlin-formula, respectively. TTE yielded SV and AVA using continuity equation. Gradients were calculated via the modified Bernoulli-equation. RESULTS: SV by PC-CMR (85 ± 31 ml) correlated strongly (r: 0.73, p < 0.001) with cine-CMR (85 ± 19 ml) without significant bias (lower and upper limits of agreement (LLoA and ULoA): - 41 ml and 44 ml, p = 0.83). In PC-CMR, mean pressure gradient correlated significantly with invasive determination (r: 0.36, p = 0.011). Mean AVA, as determined by PC-CMR during systole (0.78 ± 0.25 cm2), correlated moderately (r: 0.54, p < 0.001) with invasive AVA (0.70 ± 0.23 cm2), resulting in a small bias of 0.08 cm2 (LLoA and ULoA: - 0.36 cm2 and 0.55 cm2, p = 0.017). Inter-methodically, AVA by TTE (0.81 ± 0.23 cm2) compared to invasive determination showed similar correlations (r: 0.58, p < 0.001 with a bias of 0.11 cm2, LLoA and ULoA: - 0.30 and 0.52, p < 0.001) to PC-CMR. Intra- and interobserver reproducibility were excellent for AVA (intraclass-correlation-coefficients of 0.939 and 0.827, respectively). CONCLUSIONS: Our novel approach using continuous determination of flow-volumes and velocities with PC-CMR enables simple AVA measurement with no bias to invasive assessment. This approach highlights non-invasive AS grading through CMR, especially when TTE findings are inconclusive.

Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy.

PURPOSE: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy. METHODS: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. RESULTS: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001). CONCLUSIONS: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients.

Baseline LV ejection fraction by cardiac magnetic resonance and 2D echocardiography after ST-elevation myocardial infarction - influence of infarct location and prognostic impact.

OBJECTIVES: The comparability of left ventricular ejection fraction (LVEF) measurements by cardiac magnetic resonance (CMR) and 2D echocardiography (2DE) early after ST-elevation myocardial infarction (STEMI) remains unclear. METHODS: In this study, LVEF measured by CMR and 2DE (Simpson's method) were compared in 221 patients after STEMI treated by primary percutaneous coronary intervention. 2DE image quality was systematically assessed and studies reported by an accredited examiner. Intermodality agreement was assessed by the Bland-Altman method. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction or hospitalisation for heart failure. Patients were followed up for a median of 40.9 months (IQR 28.1-56). RESULTS: After non-anterior STEMI, LVEF measurements by 2DE (single and biplane) were consistently underestimated in comparison to CMR (CMR 55.7 ± 9.5% vs. 2DE-4CV 49 ± 8.2% (p = 0.06), 2DE-2CV 52 ± 8% (p < 0.001), 2DE-biplane 53.5 ± 7.1% (p = 0.01)). After anterior STEMI, there was no significant difference in LVEF measurements by 2DE and CMR with acceptable limits of agreement (CMR 49 ± 11% vs. 2DE-4CV 49 ± 8.2% (p = 0.8), 2DE-2CV 49 ± 9.2% (p = 0.9), 2DE-biplane 49.6 ± 8% (p = 0.5)). In total, 15% of patients experienced a MACE during follow-up. In multivariate Cox regression analysis, reduced LVEF (< 52%) as assessed by either 2DE or CMR was predictive of MACE (2DE HR = 2.57 (95% CI 1.1-6.2), p = 0.036; CMR HR = 2.51 (95% CI 1.1-5.7), p = 0.028). CONCLUSIONS: At baseline after non-anterior STEMI, 2D echocardiography significantly underestimated LVEF in comparison to CMR, whereas after anterior infarction, measurements were within acceptable limits of agreement. Both imaging modalities offered similar prognostic values when a reduced LVEF < 52% was applied. KEY POINTS: • After non-anterior STEMI, 2D-echocardiography significantly underestimated LVEF compared with cardiac MRI • An ejection fraction of < 52% in the acute post-infarct period by both 2D echocardiography and CMR offered similar prognostic values.

Non-contrast MRI protocol for TAVI guidance: quiescent-interval single-shot angiography in comparison with contrast-enhanced CT.

OBJECTIVES: To prospectively compare unenhanced quiescent-interval single-shot MR angiography (QISS-MRA) with contrast-enhanced computed tomography angiography (CTA) for contrast-free guidance in transcatheter aortic valve intervention (TAVI). METHODS: Twenty-six patients (mean age 83 ± 5 years, 15 female [58%]) referred for TAVI evaluation underwent QISS-MRA for aortoiliofemoral access guidance and non-contrast three-dimensional (3D) "whole heart" MRI for prosthesis sizing on a 1.5-T system. Contrast-enhanced CTA was performed as imaging gold standard for TAVI planning. Image quality was assessed by a 4-point Likert scale; continuous MRA and CTA measurements were compared with regression and Bland-Altman analyses. RESULTS: QISS-MRA and CTA-based measurements of aortoiliofemoral vessel diameters correlated moderately to very strong (r = 0.572 to 0.851, all p ≤ 0.002) with good to excellent inter-observer reliability (intra-class correlation coefficient (ICC) = 0.862 to 0.999, all p < 0.0001) regarding QISS assessment. Mean diameters of the infrarenal aorta and iliofemoral vessels differed significantly (bias 0.37 to 0.98 mm, p = 0.041 to < 0.0001) between the two modalities. However, inter-method decision for transfemoral access route was comparable (κ = 0.866, p < 0.0001). Aortic root parameters assessed by 3D whole heart MRI strongly correlated (r = 0.679 to 0.887, all p ≤ 0.0001) to CTA measurements. CONCLUSION: QISS-MRA provides contrast-free access route evaluation in TAVI patients with moderate to strong correlations compared with CTA and substantial inter-observer agreement. Despite some significant differences in minimal vessel diameters, inter-method agreement for transfemoral accessibility is strong. Combination with 3D whole heart MRI facilitates unenhanced TAVI guidance. KEY POINTS: • QISS-MRA and CTA inter-method agreement for transfemoral approach is strong. • QISS-MRA is a very good alternative to CTA and MRA especially in patients with Kidney Disease Outcomes Quality Initiativestages 4 and 5. • Combination of QISS-MRA and 3D "whole heart" MRI facilitates fully unenhanced TAVI guidance.

Mitral annular plane systolic excursion by cardiac MR is an easy tool for optimized prognosis assessment in ST-elevation myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the comparative prognostic value of mitral annular plane systolic excursion (MAPSE) versus left ventricular ejection fraction (LVEF), measured by cardiac magnetic resonance (CMR) imaging in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS: CMR was performed in 255 STEMI patients within 2 days (interquartile range (IQR) 2-4 days) after infarction. CMR included MAPSE measurement on CINE 4-chamber view. Patients were followed for major adverse cardiovascular events (MACE)-death, non-fatal myocardial re-infarction, stroke, and new congestive heart failure. RESULTS: Patients with MACE (n = 35, 14%, median follow-up 3 years [IQR 1-4 years]) showed significantly lower MAPSE (8 mm [7-8.8] vs. 9.6 mm [8.1-11.5], p < 0.001). The association between decreased MAPSE (< 9 mm, optimal cut-off value by c-statistics) remained significant after adjustment for independent clinical and CMR predictors of MACE. The AUC of MAPSE for the prediction of MACE was 0.74 (CI 95% 0.65-0.82), significantly higher than that of LVEF (0.61 [CI 95% 0.50-0.71]; p < 0.001). CONCLUSIONS: Reduced long-axis function assessed with MAPSE measurement using CINE CMR independently predicts long-term prognosis following STEMI. Moreover, MAPSE provided significantly higher prognostic implication in comparison with conventional LVEF measurement. KEY POINTS: • MAPSE determined by CMR independently predicts long-term prognosis following STEMI. • MACE-free survival is significantly higher in patients with MAPSE ≥ 9 mm than < 9 mm. • MAPSE provides significantly higher prognostic implication than conventional LVEF.

Prognosis-based definition of left ventricular remodeling after ST-elevation myocardial infarction.

OBJECTIVES: Cardiac magnetic resonance (CMR) is the gold-standard modality for the assessment of left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI) patients. However, the commonly used remodeling criteria have never been validated for hard clinical events. We therefore aimed to define clear CMR criteria of LV remodeling following STEMI with proven prognostic impact. METHODS: This observational study included 224 patients suffering from acute STEMI. CMR was performed within 1 week and 4 months after infarction to evaluate different remodeling criteria including relative changes in LV end-diastolic volume (%∆LVEDV), end-systolic volume (%∆LVESV), ejection fraction (%∆LVEF), and myocardial mass (%∆LVMM). Primary endpoint was the occurrence of major adverse cardiovascular events (MACE) including all-cause death, re-infarction, stroke, and new congestive heart failure 24 months following STEMI. Secondary endpoint was defined as composite of primary endpoint and cardiovascular hospitalization. The Mann-Whitney U test was applied to assess differences in LV remodeling measures between patients with and without MACE. Values for the prediction of primary and secondary endpoints were assessed by c-statistics and Cox regression analysis. RESULTS: The incidence of MACE (n = 13, 6%) was associated with higher %∆LVEDV (p = 0.002) and %∆LVMM (p = 0.02), whereas %∆LVESV and %∆LVEF were not significantly related to MACE (p > 0.05). The area under the curve (AUC) for the prediction of MACE was 0.76 (95% confidence interval [CI], 0.65-0.87) for %∆LVEDV (optimal cut-off 10%) and 0.69 (95%CI, 0.52-0.85) for %∆LVMM (optimal cut-off 5%). From all remodeling criteria, %∆LVEDV ≥ 10% showed highest hazard ratio (8.68 [95%CI, 2.39-31.56]; p = 0.001) for MACE. Regarding secondary endpoint (n = 35, 16%), also %∆LVEDV with an optimal threshold of 10% emerged as strongest prognosticator (AUC 0.66; 95%CI, 0.56-0.75; p = 0.004). CONCLUSIONS: Following revascularized STEMI, %∆LVEDV ≥ 10% showed strongest association with clinical outcome, suggesting this criterion as preferred CMR-based definition of post-STEMI LV remodeling. KEY POINTS: • CMR-determined %∆LVEDV and %∆LVMM were significantly associated with MACE following STEMI. • Neither %∆LVESV nor %∆LVEF showed a significant relation to MACE. • %∆LVEDV ≥ 10 was revealed as LV remodeling definition with highest prognostic validity.

Complete versus simplified Selvester QRS score for infarct severity assessment in ST-elevation myocardial infarction.

BACKGROUND: Complete and simplified Selvester QRS score have been proposed as valuable clinical tool for estimating myocardial damage in patients with ST-elevation myocardial infarction (STEMI). We sought to comprehensively compare both scoring systems for the prediction of myocardial and microvascular injury assessed by cardiac magnetic resonance (CMR) imaging in patients with acute STEMI. METHODS: In this prospective observational study, 201 revascularized STEMI patients were included. Electrocardiography was conducted at a median of 2 (interquartile range 1-4) days after the index event to evaluate the complete and simplified QRS scores. CMR was performed within 1 week and 4 months thereafter to determine acute and chronic infarct size (IS) as well as microvascular obstruction (MVO). RESULTS: Complete and simplified QRS score showed comparable predictive value for acute (area under the curve (AUC) = 0.64 vs. 0.67) and chronic IS (AUC = 0.63 vs. 0.68) as well as for MVO (AUC = 0.64 vs. 0.66). Peak high sensitivity cardiac troponin T (hs-cTnT) showed an AUC of 0.88 for acute IS and 0.91 for chronic IS, respectively. For the prediction of MVO, peak hs-cTnT represented an AUC of 0.81. CONCLUSIONS: In reperfused STEMI, complete and simplified QRS score displayed comparable value for the prediction of acute and chronic myocardial as well as microvascular damage. However, both QRS scoring systems provided inferior predictive validity, compared to peak hs-cTnT, the clinical reference method for IS estimation.

Is MRI equivalent to CT in the guidance of TAVR? A pilot study.

OBJECTIVES: To compare a comprehensive cardiovascular magnetic resonance imaging (MRI) protocol with contrast-enhanced computed tomography angiography (CTA) for guidance in transcatheter aortic valve replacement (TAVR) evaluation. METHODS AND RESULTS: Non-contrast three-dimensional (3D) 'whole heart' MRI imaging for aortic annulus sizing and measurements of coronary ostia heights, contrast-enhanced MRI angiography (MRA) for evaluation of transfemoral routes as well as aortoiliofemoral-CTA were performed in 16 patients referred for evaluation of TAVR. Aortic annulus measurements by MRI and CTA showed a very strong correlation (r=0.956, p<0.0001; effective annulus area for MRI 430±74 vs. 428±78 mm2 for CTA, p=0.629). Regarding decision for valve size there was complete consistency between MRI and CTA. Moreover, vessel luminal diameters and angulations of aortoiliofemoral access as measured by MRA and CTA showed overall very strong correlations (r= 0.819 to 0.996, all p<0.001), the agreement of minimal vessel diameter between the two modalities revealed a bias of 0.02 mm (upper and lower limit of agreement: 1.02 mm and -0.98 mm). CONCLUSIONS: In patients referred for TAVR, MRI measurements of aortic annulus and minimal aortoiliofemoral diameters showed good to excellent agreement. Decisions based on MRI measurements regrading prosthesis sizing and transfemoral access would not have modified TAVR-strategy as compared to a CTA-based choice. KEY POINTS: • 'Whole heart' MRI and CTA measurements of aortic annulus correlate very strongly. • MRI- and CTA-based prostheses sizing are in excellent agreement. • MRA and CTA equally guide TAVR access strategy.

Acute kidney injury is associated with microvascular myocardial damage following myocardial infarction.

Acute kidney injury (AKI) is a frequent complication in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention. However, the pathophysiology of AKI in this setting is complex and goes beyond the administration of contrast media. Studies assessing the impact of infarct characteristics on AKI are currently lacking. Therefore, we investigated the association of AKI with myocardial as well as microvascular injury in an initial total of 361 consecutive STEMI patients treated by primary percutaneous coronary intervention. Of these, 318 patients were included in final analysis. Serum creatinine was measured on admission as well as 24, 48, and 72 hours thereafter with AKI defined as an increase in serum creatinine of 0.3 mg/dl or more. Cardiac magnetic resonance (CMR) scans were performed in the first week after infarction, with microvascular injury visualized by late gadolinium enhancement CMR defined as any region of hypoenhancement within the hyperenhanced area of infarction. Sixteen patients developed AKI. They showed significantly lower left ventricular ejection fraction (45[interquartile range 40-52]% vs. 54[47-59]%), larger infarct size (21[15-35]% vs. 12[7-22]%) of left ventricular myocardial mass, and more frequent microvascular injury (81 vs. 46%) than those free of AKI. Meaningfully, in multivariate analysis including all CMR data, microvascular injury was the sole independent predictor of AKI (odds ratio 6.74, 95% confidence interval of 1.49-30.43). Thus, among revascularized STEMI patients, the presence of microvascular injury assessed by CMR was independently associated with an increased risk of AKI. This suggests a potential pathophysiological link between cardiac microvascular disease and renal injury following STEMI.

Relationship between diabetes and ischaemic injury among patients with revascularized ST-elevation myocardial infarction.

AIMS: Studies comparing reperfusion efficacy and myocardial damage between diabetic and non-diabetic patients with ST-elevation myocardial infarction (STEMI) are scarce and have reported conflicting results. The aim was to investigate the impact of preadmission diabetic status on myocardial salvage and damage as determined by cardiac magnetic resonance (CMR), and to evaluate its prognostic relevance. MATERIALS AND METHODS: We enrolled 792 patients with STEMI at 8 sites. CMR core laboratory analysis was performed to determine infarct characteristics. Major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal re-infarction and new congestive heart failure, were recorded at 12 months. Patients were categorized according to preexisting diabetes mellitus (DM), and according to insulin-treated DM (ITDM) and non-insulin-treated DM (NITDM). RESULTS: One-hundred and sixty (20%) patients had DM and 74 (9%) were insulin-treated. There was no difference in the myocardial salvage index, infarct size, microvascular obstruction and left ventricular ejection fraction between all patient groups (all P > .05). Patients with DM were at higher risk of MACE (11% vs 6%, P = .03) than non-DM patients. After stratification according to preadmission anti-diabetic therapy, MACE rate was comparable between NITDM and non-DM (P > .05), whereas the group of ITDM patients had significantly worse outcome (P < .001). CONCLUSIONS: Diabetic patients with STEMI, especially those having ITDM, had an increased risk of MACE. The adverse clinical outcome was, however, not explained by an impact of DM on reperfusion success or myocardial damage. Clinical trial registry number: NCT00712101.

AMP-activated protein kinase α1-sensitive activation of AP-1 in cardiomyocytes.

AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial role in the response to cell stress. In the failing heart, an isoform shift of the predominant Ampkα2 to the Ampkα1 was observed. The present study explored possible isoform specific effects of Ampkα1 in cardiomyocytes. To this end, experiments were performed in HL-1 cardiomyocytes, as well as in Ampkα1-deficient and corresponding wild-type mice and mice following AAV9-mediated cardiac overexpression of constitutively active Ampkα1. As a result, in HL-1 cardiomyocytes, overexpression of constitutively active Ampkα1 increased the phosphorylation of Pkcζ. Constitutively active Ampkα1 further increased AP-1-dependent transcriptional activity and mRNA expression of the AP-1 target genes c-Fos, Il6 and Ncx1, effects blunted by Pkcζ silencing. In HL-1 cardiomyocytes, angiotensin-II activated AP-1, an effect blunted by silencing of Ampkα1 and Pkcζ, but not of Ampkα2. In wild-type mice, angiotensin-II infusion increased cardiac Ampkα1 and cardiac Pkcζ protein levels, as well as c-Fos, Il6 and Ncx1 mRNA expression, effects blunted in Ampkα1-deficient mice. Pressure overload by transverse aortic constriction (TAC) similarly increased cardiac Ampkα1 and Pkcζ abundance as well as c-Fos, Il6 and Ncx1 mRNA expression, effects again blunted in Ampkα1-deficient mice. AAV9-mediated cardiac overexpression of constitutively active Ampkα1 increased Pkcζ protein abundance and the mRNA expression of c-Fos, Il6 and Ncx1 in cardiac tissue. In conclusion, Ampkα1 promotes myocardial AP-1 activation in a Pkcζ-dependent manner and thus contributes to cardiac stress signaling.

Novel biomarkers predicting cardiac function after acute myocardial infarction.

BACKGROUND: Measurement of biomarkers provides a cost-effective and widely available method to estimate cardiac dysfunction and clinical outcome of patients with acute myocardial infarction (AMI). SOURCES OF DATA: PubMed entries with terms 'myocardial infarction' and the respective biomarker. AREAS OF AGREEMENT: Cardiac troponins and natriuretic peptides are closely related to left ventricular dysfunction and the occurrence of adverse clinical events following AMI. AREAS OF CONTENTION: The incremental value of novel biomarkers is controversial. FUTURE DIRECTIONS: The combination of traditional and novel biomarkers might further improve risk stratification of patients with AMI. SEARCH STRATEGY: We searched all entries on the PubMed database with the MeSH terms 'myocardial infarction' and 'cardiac troponins', 'natriuretic peptides', 'copeptin', galectin-3', 'corin', 'fetuin-A', 'adiponectin' and 'microRNA'.

Cardiac index after acute ST-segment elevation myocardial infarction measured with phase-contrast cardiac magnetic resonance imaging.

OBJECTIVES: Phase-contrast CMR (PC-CMR) might provide a fast and robust non-invasive determination of left ventricular function in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: Cine sequences in the left-ventricular (LV) short-axis and free-breathing, retrospectively gated PC-CMR were performed in 90 patients with first acute STEMI and 15 healthy volunteers. Inter- and intra-observer agreement was determined. The correlations of clinical variables (age, gender, ejection fraction, NT pro-brain natriuretic peptide [NT-proBNP] with cardiac index (CI) were calculated. RESULTS: For CI, there was a strong agreement of cine CMR with PC-CMR in healthy volunteers (r: 0.82, mean difference: -0.14 l/min/m(2), error ± 23 %). Agreement was lower in STEMI patients (r: 0.61, mean difference: -0.17 l/min/m(2), error ± 32 %). In STEMI patients, CI measured with PC-CMR showed lower intra-observer (1 % vs. 9 %) and similar inter-observer variability (9 % vs. 12 %) compared to cine CMR. CI was significantly correlated with age, ejection fraction and NT-proBNP values in STEMI patients. DISCUSSION: The agreement of PC-CMR and cine CMR for the determination of CI is lower in STEMI patients than in healthy volunteers. After acute STEMI, CI measured with PC-CMR decreases with age, LV ejection fraction and higher NT-proBNP. KEY POINTS: • Cine CMR and PC-CMR correlate well in healthy volunteers. • Agreement is lower in STEMI patients. • Cardiac Output should be measured with one method longitudinally. • Cardiac output decreases with age after myocardial infarction.

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. METHODS: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). RESULTS: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). CONCLUSIONS: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CLINICAL TRIAL REGISTRATION: CHILL-MI: NCT01379261 . MITOCARE: NCT01374321 .

Antecedent hypertension and myocardial injury in patients with reperfused ST-elevation myocardial infarction.

BACKGROUND: Antecedent hypertension is associated with poor outcome in patients with ST-elevation myocardial infarction (STEMI). Whether differences in myocardial salvage, infarct size and microvascular injury contribute to the adverse outcome is unknown. We investigated the association between antecedent hypertension and cardiovascular magnetic resonance (CMR) parameters of myocardial salvage and damage in a multicenter CMR substudy of the AIDA-STEMI trial (Abciximab Intracoronary versus intravenously Drug Application in ST-elevation myocardial infarction). METHODS: We analyzed 792 consecutive STEMI patients reperfused within 12 h after symptom onset. Patients underwent CMR imaging for assessment of myocardial salvage, infarct size and microvascular obstruction within 10 days after infarction. Major adverse cardiac events (MACE) were recorded at 12-month follow-up. RESULTS: Antecedent hypertension was present in 540 patients (68 %) and was associated with a significantly increased baseline risk profile (advanced age, higher body mass index, higher incidence of diabetes, hypercholesterolemia, previous angioplasty and multivessel disease, p < 0.001 for all). MACE were more frequent in patients with hypertension as compared to patients without hypertension (45 [8 %] vs. 8 [3 %], p < 0.01). Antecedent hypertension remained an independent predictor of MACE after multivariate adjustment (hazard ratio 3.42 [confidence interval 1.45-8.08], p < 0.01). There was, however, no significant difference in the area at risk, infarct size, myocardial salvage index, extent of microvascular obstruction, and left ventricular ejection fraction between the groups (all p > 0.05). CONCLUSION: Despite a higher rate of MACE in contemporary reperfused STEMI patients with antecedent hypertension, there was no difference in reperfusion efficacy, infarct size and reperfusion injury as visualized by CMR. TRIAL REGISTRATION: NCT00712101 .