Pericardial Fat Is Associated With Less Severe Multiorgan Failure Over Time in Patients With Coronavirus Disease-19: The Maastricht Intensive Care COVID Cohort.

PURPOSE: Pericardial fat (PF) and epicardial adipose tissue (EAT) may enhance the proinflammatory response in corona virus-19 (COVID-19) patients. Higher PF and EAT volumes might result in multiorgan failure and explain unfavorable trajectories.The aim of this study was to examine the association between the volume of PF and EAT and multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated COVID-19 patients with an available chest computed tomography were prospectively included (March-June 2020). PF and EAT volumes were quantified using chest computed tomography scans. Patients were categorized into sex-specific PF and EAT tertiles. Variables to calculate Sequential Organ Failure Assessment (SOFA) scores were collected daily to indicate multiorgan failure. Linear mixed-effects regression was used to investigate the association between tertiles for PF and EAT volumes separately and serial SOFA scores over time. All models were adjusted. RESULTS: Sixty-three patients were divided into PF and EAT tertiles, with median PF volumes of 131.4 mL (IQR [interquartile range]: 115.7, 143.2 mL), 199.8 mL (IQR: 175.9, 221.6 mL), and 318.8 mL (IQR: 281.9, 376.8 mL) and median EAT volumes of 69.6 mL (IQR: 57.0, 79.4 mL), 107.9 mL (IQR: 104.6, 115.1 mL), and 163.8 mL (IQR: 146.5, 203.1 mL). Patients in the highest PF tertile had a statistically significantly lower SOFA score over time (1.3 [-2.5, -0.1], P =0.033) compared with the lowest PF tertile. EAT tertiles were not significantly associated with SOFA scores over time. CONCLUSION: A higher PF volume is associated with less multiorgan failure in mechanically ventilated COVID-19 patients. EAT volumes were not associated with multiorgan failure.

A case report of a myocardial ischaemic attack: a novel hyperenhancement pattern on cardiac magnetic resonance in focal ischaemic injury.

Background: Delayed enhancement cardiac magnetic resonance (DE-CMR) is the reference standard for the non-invasive assessment of myocardial fibrosis. DE-CMR is able to distinguish ischaemic from non-ischaemic aetiologies based on differences in hyperenhancement distribution patterns. Hyperenhancement caused by ischaemic injury typically involves the endocardium, while hyperenhancement confined to the mid- and epicardial layers of the myocardium suggests a non-ischaemic aetiology. Case summary: This is a case of a 20-year-old male with an unremarkable medical history with an acute ST-elevation myocardial infarction. DE-CMR revealed two distinct patterns of hyperenhancement: (i) a 'normal' wavefront-ischaemic pattern, and (ii) multiple atypical mid-wall and epicardial areas of focal hyperenhancement. Invasive coronary angiography (ICA) and coronary computed tomographic angiography (CCTA) showed multiple intracoronary thrombi and distal emboli in the left anterior descending, ramus circumflexus, and in smaller branches of the LCA. All hyperenhancement patterns observed on DE-CMR perfectly matched the distribution territories of the affected coronary arteries. Discussion: This case with an acute myocardial infarction showed intracoronary thrombi and emboli on ICA and CCTA. Interestingly, DE-CMR showed two different patterns of hyperenhancement in the same territories of the coronary thrombi. This observation may challenge the concept that these non-endocardial areas of hyperenhancement on DE-CMR are always of non-ischaemic aetiology. It is hypothesized that occlusion of smaller distal branches of the coronary arteries may result in mid-wall or epicardial fibrosis as opposed to subendocardial fibrosis commonly found in patients with a large epicardial coronary occlusion. Clinicians should be aware of these atypical patterns to be able to initiate adequate medical therapy.

Left ventricular function, strain, and infarct characteristics in patients with transient ST-segment elevation myocardial infarction compared to ST-segment and non-ST-segment elevation myocardial infarctions.

AIMS: This study aims to explore cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) function, strain, and infarct size characteristics in patients with transient ST-segment elevation myocardial infarction (TSTEMI) compared to patients with ST-segment and non-ST-segment elevation myocardial infarctions (STEMI and NSTEMI, respectively). METHODS AND RESULTS: In total, 407 patients were enrolled in this multicentre observational prospective cohort study. All patients underwent CMR examination 2-8 days after the index event. CMR cine imaging was performed for functional assessment and late gadolinium enhancement to determine infarct size and identify microvascular obstruction (MVO). TSTEMI patients demonstrated the highest LV ejection fraction and the most preserved global LV strain (longitudinal, circumferential, and radial) across the three groups (overall P ≤ 0.001). The CMR-defined infarction was less frequently observed in TSTEMI than in STEMI patients [77 (65%) vs. 124 (98%), P < 0.001] but was comparable with NSTEMI patients [77 (65%) vs. 66 (70%), P = 0.44]. A remarkably smaller infarct size was seen in TSTEMI compared to STEMI patients [1.4 g (0.0-3.9) vs. 13.5 g (5.3-26.8), P < 0.001], whereas infarct size was not significantly different from that in NSTEMI patients [1.4 g (0.0-3.9) vs. 2.1 g (0.0-8.6), P = 0.06]. Whilst the presence of MVO was less frequent in TSTEMI compared to STEMI patients [5 (4%) vs. 53 (31%), P < 0.001], no significant difference was seen compared to NSTEMI patients [5 (4%) vs. 5 (5%), P = 0.72]. CONCLUSION: TSTEMI yielded favourable cardiac LV function, strain, and infarct-related scar mass compared to STEMI and NSTEMI. LV function and infarct characteristics of TSTEMI tend to be more similar to NSTEMI than STEMI.

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

BACKGROUND: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI. METHODS: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added. RESULTS: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively. CONCLUSION: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI. TRIAL REGISTRATION: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.

Epicardial Surface Area of Infarction: A Stable Surrogate of Microvascular Obstruction in Acute Myocardial Infarction.

BACKGROUND: Microvascular obstruction (MO) is a pathophysiologic complication of acute myocardial infarction that portends poor prognosis; however, it is transient and disappears with infarct healing. Much remains unknown regarding its pathophysiology and whether there are predictors of MO that could function as stable surrogates. We tested for clinical and cardiovascular magnetic resonance predictors of MO to gain insight into its pathophysiology and to find a stable surrogate. METHODS: Three hundred two consecutive patients from 2 centers underwent cardiovascular magnetic resonance within 2 weeks of first acute myocardial infarction. Three measures of infarct morphology: infarct size, transmurality, and a new index-the epicardial surface area (EpiSA) of full-thickness infarction-were quantified on delayed-enhancement cardiovascular magnetic resonance. RESULTS: Considering all clinical characteristics, only measures of infarct morphology were independent predictors of MO. EpiSA was the strongest predictor of MO and provided incremental predictive value beyond that of infarct size and transmurality (P<0.0001). In patients with 3-month follow-up cardiovascular magnetic resonance (n=81), EpiSA extent remained stable while MO disappeared, and EpiSA was a predictor of adverse ventricular remodeling. After 20 months of follow-up, 11 died and 1 had heart transplantation. Patients with an EpiSA larger than the median value (≥6%) had worse outcome than those with less than the median value (adverse events: 6.4% versus 1.9%, P=0.045). CONCLUSIONS: The EpiSA of infarction is a novel index of infarct morphology which accurately predicts MO during the first 2 weeks of MI, but unlike MO, does not disappear with infarct healing. This index has potential as a stable surrogate of the presence of acute MO and may be useful as a predictor of adverse remodeling and outcome which is less dependent on the time window of patient assessment.

MINOCA: The caveat of absence of coronary obstruction in myocardial infarction.

AIMS: Whether patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) have better outcomes than patients with obstructive coronary artery disease remains contradictory. The current study focussed on the clinical profile and prognosis of MINOCA patients. METHODS AND RESULTS: We performed a retrospective analysis of patients with acute coronary syndrome (ACS) admitted to the Isala hospital in Zwolle, the Netherlands, between 2006 and 2014. A total of 7693 patients were categorized into three groups: MINOCA, single-vessel obstructive ACS (SV-ACS), and multi-vessel obstructive ACS (MV-ACS). MINOCA patients (5.2% of the total population) were more likely to be female (51.5% vs. 30.3% and 26.0% in SV-ACS and MV-ACS, respectively, p < 0.001 for both). The prevalence of risk factors in the MINOCA group was in between the SV-ACS and MV-ACS groups. Logistic regression revealed a lower odds of dying in SV-ACS (odds ratio (OR) = 0.70 (p = 0.04)) and a similar odds in MV-ACS (OR = 0.88, p = 0.45) compared to MINOCA. CONCLUSIONS: Patients with MINOCA show an 'intermediate' risk profile with mortality rates in between those of both ACS groups. Hence, MINOCA should be recognised as a potential risk factor for mortality, requiring adequate treatment and follow-up.

Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Patients with non-ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease. OBJECTIVES: This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA. METHODS: This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively. RESULTS: The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001). CONCLUSIONS: A novel strategy of implementing CMR or CTA first in the diagnostic process in non-ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.

Identifying the Infarct-Related Artery in Patients With Non-ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Determining the infarct-related artery (IRA) in non-ST-segment-elevation myocardial infarction (MI) can be challenging. Delayed-enhancement cardiac magnetic resonance (DE-CMR) can accurately identify small MIs. The purpose of this study was to determine whether DE-CMR improves the ability to identify the IRA in patients with non-ST-segment-elevation MI. METHODS AND RESULTS: In this 3-center, prospective study, we enrolled 114 patients presenting with their first MI. Patients underwent DE-CMR followed by coronary angiography. The interventional cardiologist was blinded to the DE-CMR results. Later, coronary angiography and DE-CMR images were reviewed independently and blindly for identification of the IRA. The pattern of DE-CMR hyperenhancement was also used to determine whether there was a nonischemic pathogenesis for myocardial necrosis. The IRA was not identifiable by coronary angiography in 37% of patients (n=42). In these, the IRA or a new noncoronary artery disease diagnosis was identified by DE-CMR in 60% and 19% of patients, respectively. Even in patients with an IRA determined by coronary angiography, a different IRA or a noncoronary artery disease diagnosis was identified by DE-CMR in 14% and 13%, respectively. Overall, DE-CMR led to a new IRA diagnosis in 31%, a diagnosis of nonischemic pathogenesis in 15%, or either in 46% (95% CI, 37%-55%) of patients. Of 55 patients undergoing revascularization, 27% had revascularization solely to nonculprit coronary artery territories as determined by DE-CMR. CONCLUSIONS: Identification of the IRA by coronary angiography can be challenging in patients with non-ST-segment-elevation MI. In nearly half, DE-CMR may lead to a new IRA diagnosis or elucidate a nonischemic pathogenesis. Revascularization solely of coronary arteries that are believed to be nonculprit arteries by DE-CMR is not uncommon.

Adding Speckle-Tracking Echocardiography to Visual Assessment of Systolic Wall Motion Abnormalities Improves the Detection of Myocardial Infarction.

BACKGROUND: The aim of this study was to investigate whether speckle-tracking echocardiography (STE) improves the detection of myocardial infarction (MI) over visual assessment of systolic wall motion abnormalities (SWMAs) using delayed enhancement cardiac magnetic resonance imaging as a reference. METHODS: Transthoracic echocardiography was performed in 95 patients with first ST segment elevation MI 110 days (interquartile range, 97-171 days) after MI and in 48 healthy control subjects. Two experienced observers independently assessed SWMAs. Separately, longitudinal peak negative, peak systolic, end-systolic, global strain, and strain rate were measured and averaged for the American Heart Association-recommended coronary artery perfusion territories. Receiver operating characteristic analysis was used to determine a single optimal cutoff value for each strain parameter. The diagnostic accuracy of an algorithm combining visual assessment and STE was evaluated. RESULTS: Median infarct size and transmurality were 15% (interquartile range, 7%-24%) and 64% (interquartile range, 46%-78%), respectively. Sensitivity, specificity, and accuracy of visual assessment to detect MI were 74% (95% CI, 63%-82%), 85% (95% CI, 72%-93%), and 78% (95% CI, 70%-84%), respectively. Among the strain parameters, SR had the highest diagnostic accuracy (area under the curve, 0.88; 95% CI, 0.83-0.94; cutoff value, -0.97 sec-1). The combination with STE improved sensitivity compared with visual assessment alone (94%; 95% CI, 86%-97%; P < .001), minimally affecting specificity (79%; 95% CI, 65%-89%; P = .607). Overall accuracy improved to 89% (95% CI, 82%-93%; P = .011). Multivariate analysis accounting for age and sex demonstrated that SR was independently associated with MI (odds ratio, 2.0; 95% CI, 1.6-2.7). CONCLUSIONS: The sensitivity and diagnostic accuracy of visually detecting chronic MI by assessing SWMAs are moderate but substantially improve when adding STE.

[Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels]. / Acute pijn op de borst zonder afwijkend troponine.

BACKGROUND: Normal high sensitivity cardiac troponin (hs-cTn) assays rule out acute myocardial infarction (AMI) with great accuracy, but additional non-invasive testing is frequently ordered. This observational study evaluates whether clinical characteristics can contribute to risk stratification and could guide referral for additional testing. METHODS: This observational study included 918 patients with acute chest pain and normal hs-cTnT values. Major adverse cardiac events (MACE) and non-invasive test results were assessed during one-year follow-up. Patients were classified as low and high risk based on clinical characteristics. RESULTS: In total, 6,4% of patients experienced MACE during follow-up and mainly comprised revascularisations (86%). Absence of both recent abnormal stress test and suspicious history identified 86% of patients. These patients were at very low risk for MACE (0,4% in 30-days). Despite this, the majority (287/345=83%) of additional tests were performed in low risk patients, with 8% abnormal test findings (positive predictive value for MACE was 17%). The diagnostic yield was significantly higher in the remaining higher risk patients, 40% abnormal test findings and a positive predictive value of 70% for MACE. CONCLUSION: Clinical characteristics can be used to identify low risk patients with acute chest pain and normal hs-cTnT levels. Current strategies in the emergency department result in numerous additional tests, which are mostly ordered in patients at very low risk and have a low diagnostic yield.

Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels.

BACKGROUND: Normal high sensitivity cardiac troponin (hs-cTn) assays rule out acute myocardial infarction (AMI) with great accuracy, but additional non-invasive testing is frequently ordered. This observational study evaluates whether clinical characteristics can contribute to risk stratification and could guide referral for additional testing. METHODS: 918 serial patients with acute chest pain and normal hs-cTnT levels were prospectively included. Major adverse cardiac events (MACE) and non-invasive test results were assessed during one-year follow-up. Patients were classified as low and high risk based on clinical characteristics. RESULTS: MACE occurred in 6.1% of patients and mainly comprised revascularizations (86%). A recent abnormal stress test, suspicious history, a positive family history and higher baseline hs-cTnT levels were independent predictors of MACE with odds ratios of 16.00 (95%CI:6.25-40.96), 16.43 (6.36-42.45), 2.33 (1.22-4.42) and 1.10 (1.01-1.21), respectively. Absence of both recent abnormal stress test and suspicious history identified 86% of patients. These patients were at very low risk for MACE (0.4% in 30-days and 2.3% in one-year). Despite this, the majority (287/345 = 83%) of additional tests were performed in low risk patients, with <10% abnormal test findings. The diagnostic yield was significantly higher in the remaining higher risk patients, 40% abnormal test findings and a positive predictive value of 70% for MACE. Similar results were observed in patients without known coronary artery disease. CONCLUSIONS: Clinical characteristics can be used to identify low risk patients with acute chest pain and normal hs-cTnT levels. Current strategies in the emergency department result in numerous additional tests, which are mostly ordered in patients at very low risk and have a low diagnostic yield.

Bursts of reperfusion arrhythmias occur independently of area at risk size and are the first marker of reperfusion injury.

BACKGROUND: The presence of reperfusion ventricular arrhythmias (VA) has been shown to correlate with larger infarct size (IS). However it is unclear whether the initial area at risk (AAR), also a determining factor for IS, is responsible for this correlation. We hypothesized that IS would be significantly larger in the presence of VA, while AAR would not differ. METHODS: 68 STEMI patients from the MAST study with 24-hour, continuous, 12­lead Holter monitoring initiated prior to primary percutaneous coronary intervention (PCI) resulting in TIMI 3 flow post PCI were included. VA bursts were identified against subject-specific background VA rates using a previously validated statistical outlier method. IS, and infarct endocardial surface area (ESA) were obtained using CMR at mean 4.9 days after admission. Holter and CMR results were determined in core laboratories blinded to all other data. RESULTS: VA bursts were present in 69% (45/65) of patients. No significant differences were found for demographic characteristics, comorbidities, infarct location, number of diseased coronary vessels, or duration of ischemia between groups with and without VA burst. IS was significantly smaller in the group without VA bursts (median 9.3% vs 17.0%; p = 0.025). Infarct ESA did not significantly differ between the population with and without VA burst; median 24.3% vs 20.0%; p = 0.15. CONCLUSION: VA bursts are a marker for larger IS independent of AAR, assessed by surrogate markers. These findings support the hypothesis that VA bursts are a marker of reperfusion damage occurring downstream at myocellular level.

Long-Term Prognostic Implications of Previous Silent Myocardial Infarction in Patients Presenting With Acute Myocardial Infarction.

OBJECTIVES: This study investigated the prevalence of silent myocardial infarction (MI) in patients presenting with first acute myocardial infarction (AMI), and its relation with mortality and major adverse cardiovascular events (MACE) at long-term follow-up. BACKGROUND: Up to 54% of MI occurs without apparent symptoms. The prevalence and long-term prognostic implications of previous silent MI in patients presenting with seemingly first AMI are unclear. METHODS: A 2-center observational longitudinal study was performed in 392 patients presenting with first AMI between 2003 and 2013, who underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) examination within 14 days post-AMI. Silent MI was assessed on LGE-CMR images by identifying regions of hyperenhancement with an ischemic distribution pattern in other territories than the AMI. Mortality and MACE (all-cause death, reinfarction, coronary artery bypass grafting, and ischemic stroke) were assessed at 6.8 ± 2.9 years follow-up. RESULTS: Thirty-two patients (8.2%) showed silent MI on LGE-CMR. Compared with patients without silent MI, mortality risk was higher in patients with silent MI (hazard ratio: 3.87; 95% confidence interval: 1.21 to 12.38; p = 0.023), as was risk of MACE (hazard ratio: 3.10; 95% confidence interval: 1.22 to 7.86; p = 0.017), both independent from clinical and infarction-related characteristics. CONCLUSIONS: Silent MI occurred in 8.2% of patients presenting with first AMI and was independently related to poorer long-term clinical outcome, with a more than 3-fold risk of mortality and MACE. Silent MI holds prognostic value over important traditional prognosticators in the setting of AMI, indicating that these patients represent a high-risk subgroup warranting clinical awareness.

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.

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.

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.

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.

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.