Martijn W. Smulders

Performance of angiographic, electrocardiographic and MRI methods to assess the area at risk in acute myocardial infarction

Objective Validation of methods to assess the area at risk (AAR) in patients with ST elevation myocardial infarction is limited. A study was undertaken to test different AAR methods using established physiological concepts to provide a reference standard. Main outcome measured In 78 reperfused patients with first ST elevation myocardial infarction, AAR was measured by electrocardiographic (Aldrich), angiographic (Bypass Angioplasty Revascularization Investigation (BARI), APPROACH) and cardiovascular magnetic resonance methods (T2-weighted hyperintensity and delayed enhanced endocardial surface area (ESA)). The following established physiological concepts were used to evaluate the AAR methods: (1) AAR size is always ≥ infarct size (IS); (2) in transmural infarcts AAR size=IS; (3) correlation between AAR size and IS increases as infarct transmurality increases; and (4) myocardial salvage ((AAR-IS)/AAR×100) is inversely related to infarct transmurality. Results Overall, 65%, 87%, 76%, 87% and 97% of patients using the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods obeyed the concept that AAR size is ≥IS. In patients with transmural infarcts (n=22), Bland–Altman analysis showed poor agreement (wide 95% limits of agreement) between AAR size and IS for the BARI, Aldrich and APPROACH methods (95% CI −22.9 to 29.6, 95% CI −28.3 to 21.3 and 95% CI −16.9 to 20.0, respectively) and better agreement for T2-weighted hyperintensity and ESA (95% CI −6.9 to 16.6 and 95% CI −4.3 to 18.0, respectively). Increasing correlation between AAR size and IS with increasing infarct transmurality was observed for the APPROACH, T2-weighted hyperintensity and ESA methods, with ESA having the highest correlation (r=0.93, p<0.001). The percentage of patients within a narrow margin (±30%) of the inverse line of identity between salvage extent and infarct transmurality was 56%, 76%, 65%, 77% and 92% for the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods, respectively, where higher percentages represent better concordance with the concept that the extent of salvage should be inversely related to infarct transmurality. Conclusions For measuring AAR, cardiovascular magnetic resonance methods are better than angiographic methods, which are better than electrocardiographic methods. Overall, ESA performed best for measuring AAR in vivo.

Incremental value of cardiovascular magnetic resonance over echocardiography in the detection of acute and chronic myocardial infarction

BackgroundAlthough echocardiography is used as a first line imaging modality, its accuracy to detect acute and chronic myocardial infarction (MI) in relation to infarct characteristics as assessed with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is not well described.MethodsOne-hundred-forty-one echocardiograms performed in 88 first acute ST-elevation MI (STEMI) patients, 2 (IQR1-4) days (n = 61) and 102 (IQR92-112) days post-MI (n = 80), were pooled with echocardiograms of 36 healthy controls. 61 acute and 80 chronic echocardiograms were available for analysis (53 patients had both acute and chronic echocardiograms). Two experienced echocardiographers, blinded to clinical and CMR data, randomly evaluated all 177 echocardiograms for segmental wall motion abnormalities (SWMA). This was compared with LGE-CMR determined infarct characteristics, performed 104 ± 11 days post-MI. Enhancement on LGE-CMR matched the infarct-related artery territory in all patients (LAD 31%, LCx 12% and RCA 57%).ResultsThe sensitivity of echocardiography to detect acute MI was 78.7% and 61.3% for chronic MI; specificity was 80.6%. Undetected MI were smaller, less transmural, and less extensive (6% [IQR3-12] vs. 15% [IQR9-24], 50 ± 14% vs. 61 ± 15%, 7 ± 3 vs. 9 ± 3 segments, p < 0.001 for all) and associated with higher left ventricular ejection fraction (LVEF) and non-anterior location as compared to detected MI (58 ± 5% vs. 46 ± 7%, p < 0.001 and 82% vs. 63%, p = 0.03). After multivariate analysis, LVEF and infarct size were the strongest independent predictors of detecting chronic MI (OR 0.78 [95%CI 0.68-0.88], p < 0.001 and OR 1.22 [95%CI0.99-1.51], p = 0.06, respectively). Increasing infarct transmurality was associated with increasing SWMA (p < 0.001).ConclusionsIn patients presenting with STEMI, and thus a high likelihood of SWMA, the sensitivity of echocardiography to detect SWMA was higher in the acute than the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Further work is needed to assess the diagnostic accuracy in patients with non-STEMI.

Comparison of the prognostic value of negative non-invasive cardiac investigations in patients with suspected or known coronary artery disease–a meta-analysis

Aims To compare the prognostic value of negative non-invasive cardiac investigations (coronary computed tomographic angiography [CCTA], cardiovascular magnetic resonance [CMR], exercise electrocardiographic testing [EET], positron emission tomography [PET], stress-echocardiography [SE], and single-photon emission tomography [SPECT]) in patients with suspected or known coronary artery disease (CAD) and to explore the effect of adjustment for population event risk and presence of CAD. Methods and results MEDLINE/PubMed database, EMBASE and Cochrane Library were searched from January-1990 to April-2015 for studies reporting annual event rates (AER) of myocardial infarction (MI) and cardiac death. Pooled estimates of AERs were calculated using a DerSimonian and Laird random-effects model. Multivariable linear meta-regression analysis was performed to compare the AER after a negative test result between modalities and to adjust for population event risk and proportion of patients with CAD. In 165 studies (122,721 patients), pooled AERs after negative test results differed significantly between modalities ranging from 0.32% for CCTA to 1.66% for SE, P < 0.001. However, the AER after a negative test result was positively correlated (r = 0.726, P < 0.001) with population event risk. Adjusting for population event risk and proportion of patients with CAD resulted in more similar event rates after a negative test result. Conclusion This meta-analysis is the first study comparing the prognostic value of all available non-invasive cardiac investigations. Outcome differences between modalities after a negative test result are profoundly influenced by large variations in population event risk and a negative test result for all modalities conveys an excellent prognosis for patients with suspected or known CAD.

Performance of CMR Methods for Differentiating Acute From Chronic MI

OBJECTIVES The purpose of this study was to assess the performance of cardiac magnetic resonance (CMR) methods for discriminating acute from chronic myocardial infarction (MI). BACKGROUND Although T2-weighted CMR is thought to be accurate in differentiating acute from chronic MI, few studies have reported on diagnostic accuracy, and these generally compared extremes in infarct age (e.g., <1 week old vs. more than 6 months old) and did not evaluate other CMR methods that could be informative. METHODS A total of 221 CMR studies were performed at various time points after ST-segment elevation myocardial infarction in 117 consecutive patients without a history of MI or revascularization enrolled prospectively at 2 centers. Imaging markers of acute MI (<1 month) were T2 hyperintensity on double inversion recovery turbo spin echo (DIR-TSE) images, microvascular obstruction (MO) on delayed-enhancement CMR, and focally increased end-diastolic wall thickness (EDWT) on cine-CMR. RESULTS The prevalence of T2-DIR-TSE hyperintensity decreased with infarct age but remained substantial up to 6 months post-MI. In contrast, the prevalence of both MO and increased EDWT dropped sharply after 1 month. T2-DIR-TSE sensitivity, specificity, and accuracy for identifying acute MI were 88%, 66%, and 77% compared with 73%, 97%, and 85%, respectively, for the combination of MO or increased EDWT. On multivariable analysis, persistence of T2-hyperintensity in intermediate-age infarcts (1 to 6 months old) was predicted by larger infarct size, diabetes, and better T2-DIR-TSE image quality score. For infarct size ≥ 10% of the left ventricle, a simple algorithm incorporating all CMR components allowed classification of infarct age into 3 categories (<1 month old, 1 to 6 months old, and ≥ 6 months old) with 80% (95% confidence interval: 73% to 87%) accuracy. CONCLUSIONS T2-DIR-TSE hyperintensity is specific for infarcts <6 months old, whereas MO and increased EDWT are specific for infarcts <1 month old. Incorporating multiple CMR markers of acute MI and their varied longevity leads to a more precise assessment of infarct age.

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non–ST-elevation myocardial infarction patients: Design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial

BACKGROUND Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA. STUDY DESIGN In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness. CONCLUSION The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.

A novel approach for left ventricular lead placement in cardiac resynchronization therapy: Intraprocedural integration of coronary venous electroanatomic mapping with delayed enhancement cardiac magnetic resonance imaging

BACKGROUND Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response. OBJECTIVE The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar. METHODS Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline. RESULTS Integration of EAM and DE-CMR was achieved using 8.9 ± 2.8 anatomic landmarks and with accuracy of 4.7 ± 1.1 mm (mean ± SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 ± 3.45 mV vs 8.18 ± 4.02 mV [median ± interquartile range), P <.001) but correlated weakly with DE-CMR scar extent (R -0.161, P <.001) and varied widely among individual patients. CONCLUSION Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT.

Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal.

Monocytic microRNA profile associated with coronary collateral artery function in chronic total occlusion patients

An expansive collateral artery network is correlated with improved survival in case of adverse cardiac episodes. We aimed to identify cellular microRNAs (miRNA; miR) important for collateral artery growth. Chronic total occlusion (CTO) patients (n = 26) were dichotomized using pressure-derived collateral flow index (CFIp) measurements; high collateral capacity (CFIp > 0.39; n = 14) and low collateral (CFIp < 0.39; n = 12) capacity. MiRNA profiling via next generation sequencing from various monocyte phenotypes (freshly isolated monocytes, monocytes cultured without stimulant, or stimulation with lipopolysaccharide, interleukin 4, transforming growth factor beta-1, or interferon gamma) revealed significantly different miRNA expression patterns between high versus low collateral capacity patients. Validation by real-time polymerase chain reaction demonstrated significantly decreased expression of miR339-5p in all stimulated monocyte phenotypes of low collateral capacity patients. MiR339-5p showed significant correlation with CFIp values in stimulated monocytes. Ingenuity pathway analysis of predicted gene targets of miR339-5p and differential gene expression data from high versus low CFIp patients (n = 20), revealed significant association with STAT3 pathway, and also suggested a possible regulatory role for this signaling pathway. These results identify a novel association between miR339-5p and coronary collateral function. Future work examining modulation of miR339-5p and downstream effects on the STAT3 pathway and subsequent collateral vessel growth are warranted.

Predictors of Intramyocardial Hemorrhage After Reperfused ST-Segment Elevation Myocardial Infarction

Background Findings from recent studies show that microvascular injury consists of microvascular destruction and intramyocardial hemorrhage (IMH). Patients with ST‐segment elevation myocardial infarction (STEMI) with IMH show poorer prognoses than patients without IMH. Knowledge on predictors for the occurrence of IMH after STEMI is lacking. The current study aimed to investigate the prevalence and extent of IMH in patients with STEMI and its relation with periprocedural and clinical variables. Methods and Results A multicenter observational cohort study was performed in patients with successfully reperfused STEMI with cardiovascular magnetic resonance examination 5.5±1.8 days after percutaneous coronary intervention. Microvascular injury was visualized using late gadolinium enhancement and T2‐weighted cardiovascular magnetic resonance imaging for microvascular obstruction and IMH, respectively. The median was used as the cutoff value to divide the study population with presence of IMH into mild or extensive IMH. Clinical and periprocedural parameters were studied in relation to occurrence of IMH and extensive IMH, respectively. Of the 410 patients, 54% had IMH. The presence of IMH was independently associated with anterior infarction (odds ratio, 2.96; 95% CI, 1.73–5.06 [P<0.001]) and periprocedural glycoprotein IIb/IIIa inhibitor treatment (odds ratio, 2.67; 95% CI, 1.49–4.80 [P<0.001]). Extensive IMH was independently associated with anterior infarction (odds ratio, 3.76; 95% CI, 1.91–7.43 [P<0.001]). Presence and extent of IMH was associated with larger infarct size, greater extent of microvascular obstruction, larger left ventricular dimensions, and lower left ventricular ejection fraction (all P<0.001). Conclusions Occurrence of IMH was associated with anterior infarction and glycoprotein IIb/IIIa inhibitor treatment. Extensive IMH was associated with anterior infarction. IMH was associated with more severe infarction and worse short‐term left ventricular function in patients with STEMI.

A simple visual algorithm incorporating the components of a routine CMR study improves the determination of infarct age compared with T2-CMR alone.

≥1- month-old-MI as (a) individual components, (b) basic combinations, and (c) using new algorithm. T2CMR-alone was sensitive (88%) but not specific (66%) for <1-month-old-MI resulting in only moderate accuracy (77%). Using a later cutpoint for ‘acute’ MI (2-months or 3-months) did not improve accuracy since sensitivity decreased with increasing specificity. MO and increased-EDWT were very specific but not sensitive for acute MI. The basic combination of MO-or-increasedEDWT improved sensitivity (73%) while retaining specificity (97%). Basic algebraic combinations including T2-CMR did not improve overall accuracy since ‘OR’ function led to low specificity while ‘AND’ function led to low sensitivity. The new algorithm resulted in high sensitivity (92%) and specificity (90%). Accuracy (91%) was improved compared with T2-CMR alone (p<0.001) and compared with basic algebraic combinations involving T2-CMR (p<0.05). An additional benefit of the algorithm was the ability to identify intermediate-aged-MI (1-6-month-old). This was based on finding T2-hyperintensity-size < DE-infarct-size, and when present, patients had median infarct age of 110 days (IQR: 96, 115) (Figure 1). Conclusions A novel algorithm incorporating components of a routine CMR scan improves the determination of infarct age compared with T2-CMR alone. Certain CMR findings may be specific for intermediate-aged MI. Funding None.