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The year 2012 in the European Heart Journal – Cardiovascular Imaging: Part I

Thor Edvardsen, Sven Plein, Antti Saraste, Juhani Knuuti, Gerald Maurer, Patrizio Lancellotti
DOI: http://dx.doi.org/10.1093/ehjci/jet069 509-514 First published online: 13 May 2013


The new multi-modality cardiovascular imaging journal, European Heart JournalCardiovascular Imaging, was started in 2012. During its first year, the new Journal has published an impressive collection of cardiovascular studies utilizing all cardiovascular imaging modalities. We will summarize the most important studies from its first year in two articles. The present ‘Part I’ of the review will focus on studies in myocardial function, myocardial ischaemia, and emerging techniques in cardiovascular imaging.

  • Myocardial function
  • Ischaemic heart disease
  • Atherosclerosis
  • Contrast echocardiography
  • Echocardiography
  • 3D echocardiography
  • Cardiac magnetic resonance
  • Computed tomography
  • Nuclear imaging


In 2012, the former European Journal of Echocardiography became the multi-modality European Heart Journal – Cardiovascular Imaging. In its first year, the new journal has become established as an important resource for general cardiologists, specialists in all imaging modalities, and other physicians working in the field of cardiovascular imaging. In two articles, we highlight the most important studies that were published in the journal in 2012. Part I is focused on studies in myocardial function, myocardial ischaemia, and emerging techniques in cardiovascular imaging.

Myocardial function

Assessment of myocardial function is a cornerstone in the diagnosis and risk stratification of patients with cardiovascular disease. In addition to established methods, novel ways to image myocardial function continue to emerge. One of the most powerful novel methods is left ventricular (LV) global longitudinal strain (GLS) by two-dimensional (2D) speckle tracking strain. In a study published in the European HeartJournalCardiovascular Imaging, Kearney et al.1 demonstrated the prognostic impact of GLS. They studied 146 patients with different degrees of aortic stenosis (AS) who were followed for a median of 2.1 years (interquartile range: 1.8–2.4 years). GLS was a strong predictor of all-cause mortality and all but one death occurred in patients with a low GLS (>−15%). The same GLS value could also differentiate significantly between patients with and without subsequent major adverse cardiac events (MACEs). The authors concluded that GLS provided an incremental prognostic value over guideline-validated risk markers, such as haemodynamic severity, symptoms, and left ventricular ejection fraction (LVEF). Zhao et al.2 studied LV function and morphology after aortic valve replacement (AVR) for AS and its relationship with exercise capacity in 21 patients with normal LVEF after AVR. At peak exercise, maximum O2 uptake (pVO2) was significantly lower in patients than controls, but there were no differences in LVEF between the two groups before exercise and global longitudinal strain rate (GLSR) was similar between groups. Nearly, all systolic and diastolic parameters were decreased compared with baseline and controls at peak exercise. In a multivariate regression model, only GLSRs at peak exercise correlated with pVO2 in the patient group.

In a study of patients with hypertrophic cardiomyopathy, Saito et al.3 concluded that GLS could provide useful information on the extent of myocardial fibrosis. Galderisi et al.4 used the new parameter of global area strain by three-dimensional (3D) echocardiography to study 38 native hypertensive patients. They demonstrated that global area strain could detect early changes in myocardial function in these patients. Furthermore, global area strain was a comprehensive parameter of myocardial systolic deformation and was very sensitive to both changes of afterload and LV mass. The ability for inexperienced echocardiographic readers to use myocardial strain was tested in a study by Blondheim et al.5 They concluded that the automatic assessment of segmental LV wall motion could be performed by inexperienced personnel with similar results to its use by experienced readers. Reduced s′and a′ by tissue velocities were both related with poorer prognosis and were better than conventional echocardiographic measures such as LVEF to predict hospitalization and mortality.6 The European Association of Cardiovascular Imaging recommends the use of the LV mass to diagnose left ventricular hypertrophy, but many echocardiographic laboratories continue to use only the septal thickness by M-mode. Barbieri et al.7 tested the ability of these two measurements to predict mortality in 2545 individuals (mean age 61.9 ± 15.8). The best prognostic information was achieved by the LV mass and not by the septal thickness.

Ischaemic heart disease

In patients with stable coronary artery disease (CAD), the diagnostic value of the resting echocardiogram is disputed. However, the diagnostic power of GLS to detect non-obstructive CAD was tested by Montgomery et al.8 in a retrospective study. GLS in 123 consecutive patients undergoing coronary angiography was compared with the wall motion score index (WMSI) during stress echocardiography and LVEF at rest. Patients with visual detectable dysfunction and reduced LVEF at rest were excluded. A reduced LV function with GLS of −17.8% or higher had a similar accuracy to the traditional WMSI measured in stress echocardiography to discover non-obstructive CAD. The authors concluded that GLS may identify CAD in an, otherwise, undiagnosed and untreated population. Another study supporting the value of echocardiographic studies at rest was presented by Hoffmann et al.9 They used colour tissue Doppler imaging and found that s′ and e′ at rest remained independent predictors of CAD after multivariable adjustment for exercise ECG and conventional echocardiographic parameters.

Stress echocardiography has traditionally been widely used for viability guidance before revascularization procedures in CAD. The prognostic value of myocardial viability has, however, been challenged by the results of the STICH trial.10 In a review paper, in the European Heart JournalCardiovascular Imaging, however, Cortigiani et al.11 argued that myocardial viability remains a key parameter to consider in the evaluation of heart failure. They also concluded that echocardiography is the most cost-effective tool for viability assessment, and that there is no convincing evidence that the assessment of myocardial viability should be discontinued in the work-up of the chronic dysfunctional myocardium, at least, not on the basis of the STICH trial.

Numerous studies have investigated the use of non-invasive imaging in patients with acute coronary syndromes (ACS) but their clinical use has been limited, especially, in Europe. Sechtem et al.12 reviewed the current status of imaging techniques in ACS patients in the emergency department. They suggested that in accordance with the current guidelines, non-invasive imaging plays only a minor role in the acute management of patients with ST-elevation myocardial infarction (STEMI). However, in patients with non-STEMI, rest echocardiography should be performed routinely. Furthermore, cardiac magnetic resonance (CMR) and nuclear imaging have proved benefit and should be considered if further confirmation or exclusion of ischaemia and infarction is needed. The role of computed tomography angiography (CTA) remains to be determined but could be beneficial in patients with low-to-moderate likelihood of coronary artery angiography (CAD), negative troponin and inconclusive ECG.

Following acute myocardial infarction, imaging can contribute importantly to the risk stratification of patients. As summarized by Carrick and Berry13, CMR, in particular, allows a detailed characterization of myocardial infarction and infract size using late gadolinium enhancement (LGE) and area at risk from T2-weighted CMR.

Lønborg et al.14 used LGE-CMR to measure the infarct size in an observational study in 309 patients with STEMI treated with primary percutaneous intervention (PCI). The infarct size was significantly associated with the worst clinical outcome in a multivariable Cox regression analysis, which also included age, peak troponin T, LVEF, LV volume index, and heart rate, supporting the existing evidence of LGE-CMR as an independent prognostic marker of risk following STEMI.

By the subtraction of infarct size and areas at risk, the myocardial salvage index (MSI) can be derived by CMR. A study by Ubachs et al.15 added to the growing evidence base for the MSI in an elegant pre-clinical validation study. Ischaemia and reperfusion were induced in 18 pigs and native and gadolinium-enhanced T1- and T2-weighted CMR, myocardial perfusion single photon emission computed tomography (SPECT), and histology were performed ex vivo. The study showed that T2-weighted CMR agreed well with myocardial perfusion SPECT and T1-weighted CMR agreed well with histological measurement of the infarct size. In a clinical study, Canali et al.16 used the CMR-derived MSI to determine the impact of gender on reperfusion in 283 consecutive STEMI patients treated with primary PCI. Although the number of women was low (only 45 out of 283), a statistically larger MSI extent (P = 0.013), and smaller infarct size (acute CMR P < 0.001, follow-up CMR at 4 months, P < 0.001) were seen in women. At multivariate analysis, Killip class and female sex were independently associated with a higher MSI (P = 0.02, P = 0.05, respectively). These data are consistent with the previous study data and suggest that gender needs to be considered in studies in patients with STEMI.

Lønborg et al.17 also presented data on the influence of pre-infarction angina, collateral flow, and pre-procedural TIMI flow on the MSI in 200 STEMI patients. MSI was calculated from the area -at -risk on T2-weighted acute CMR and the infarct size from the follow-up LGE-CMR. Pre-infarction angina was significantly associated with MSI and patients with pre-infarction angina had higher MSI, suggesting a protective preconditioning effect. Pre-procedural TIMI was also strongly associated with MSI, while angiographically visible collateral flow to the infarct area was not.

SPECT perfusion imaging is an established method in assessing ischaemia and provides significant prognostic information. Schinkel et al.18 showed that SPECT perfusion imaging provided additional information for the prediction of the cardiac outcome even up to 9 years. They also found that perfusion imaging detected reversible perfusion defects (PDs) in 20% patients with normal exercise ECG. Thompson et al.19 studied the accuracy of SPECT perfusion imaging in detecting allograft vasculopathy, a condition that has been challenging for all non-invasive imaging methods. The authors found that perfusion imaging was not sensitive for detecting cardiac allograft vasculopathy in transplant recipients and the additional analysed parameters reflecting diastolic function did not provide beneficial information.

Owing to well-known limitations of CTA in overestimating haemodynamically significant CAD, the combination of anatomical coronary imaging with CT and functional imaging has gained increasing interest. Gaemperli et al.20 reviewed the current status of the hybrid imaging. In addition to increasingly used combination of CT angiography and PET or SPECT perfusion, also novel combination of CT and CMR as well as hybrid PET/MRI systems may have also cardiac applications. Another solution would be to obtain functional information from CT images. Choi et al.21 investigated the diagnostic performance of intracoronary gradient-based methods for this purpose. The authors found that these methods had only limited incremental value and were only moderately correlated with fractional flow reserve.

CT scanning is also increasingly used to image the left atrium and pulmonary veins using CT before catheter ablation is valuable for guidance of the procedure. Sohns et al.22 investigated whether the performed CT could be used to detect and exclude CAD in these patients. Commonly, CTA using standard CT systems in patients with atrial fibrillation has not been recommended due to problems in pacing. Sohns et al. detected that CT angiography was reliable in excluding significant CAD and could replace invasive coronary angiography in these patients. However, also in these patients, CT tended to overestimate the severity of CAD.

Atherosclerosis imaging

Cardiac CT offers useful information for risk stratification through the detection of coronary calcifications and angiography in asymptomatic subjects and symptomatic patients without known CAD as reviewed by Perrone-Filardi et al.23 The coronary calcium score (CCS) is a reasonable measure to improve the risk assessment in asymptomatic individuals at moderate risk, in whom CCS reclassifies a substantial number of subjects to different risk categories. The absence of coronary calcium is associated with a very low risk of risk of cardiovascular events in this population, but the clinical implication of zero CCS in symptomatic patients has been under debate. In 2088, patients who had undergone 64-slice cardiac CT for the assessment of chest pain, Kim et al.24 found that even in the absence of coronary artery calcification, these patients had non-negligible prevalence of obstructive CAD by CTA (4.3%). Thus, zero CCS did not guarantee favourable mid-term prognosis as composite MACEs of cardiac death, non-fatal MI, unstable angina requiring hospitalization, and late (>60 days) revascularization occurred in 1.3%. The authors concluded that CCS alone could not be used to exclude CAD in symptomatic patients referred to coronary CT angiography.

Coronary calcification correlates only weakly with the presence of obstructive CAD. Similarly, CCS and functional measures of coronary microvascular function have been found to be only weakly associated in patients without obstructive CAD. Danad et al.25 reported that, in such patients, CCS was a weaker predictor of microvascular dysfunction, detected by PET imaging of myocardial blood flow, than carotid ultrasound measurements of intima-media thickness. However, the measurement of coronary calcium is of interest for risk stratification in symptomatic patients. Bischoff et al.26 developed and validated methodology to accurately detect coronary artery calcifications in contrast-enhanced CTA images. Mylonas et al.27 validated quantification of coronary artery calcifications in positron emission tomography–computed tomography attenuation correction images. These techniques could enable comprehensive assessment of CAD including epicardial stenosis by CTA or myocardial perfusion imaging together with assessing cardiovascular risk associated with CAC without an additional radiation caused by the non-enhanced scan for calcium scoring.

Non-obstructive atherosclerotic lesions that do not cause significant anatomical luminal narrowing are common in patients with suspected CAD who are referred for coronary CTA. Segev et al.28 found that non-obstructive lesions by CTA were generally associated with the favourable outcome during intermediate follow-up in patients admitted to acute chest pain unit. The amount of MACEs (revascularization, ACS, or death) was equally low (<1%) in patients with non-obstructive CAD (n = 115) and normal coronary arteries (n = 266) by CTA 2-year-follow-up. This is somewhat in contrast to previous findings in which non-obstructive lesions had been linked with MACEs, albeit less often than obstructive lesions.

A challenge for non-invasive imaging of atherosclerosis is to find markers that could identify the plaques associated with the high risk of events. Rupture-prone or vulnerable plaques and non-invasive imaging modalities for their detection were reviewed by Joshi et al.29 Papadopoulou et al.30 reported a novel CTA marker of high-risk plaques as a result of the evaluation of coronary bifurcation atherosclerotic lesions beyond volumetric and compositional analysis by integrating information on the bifurcation angle in curved multiplanar reformat images. Interestingly, a wide bifurcation angle predicted the presence of high-risk plaque phenotype, thin cap fibroatheroma as detected by optical coherence tomography (OCT) imaging in the proximal segment. Local haemodynamic factors, in particular, low-endothelial shear stress, play a role in the localization and development of plaques with high-risk features and are related to bifurcation angle.

Epicardial adipose tissue measured in non-enhanced cardiac CT scans has been proposed as a risk marker for CAD, but its significance has remained controversial. Versteylen et al.31 measured epicardial adipose tissue in symptomatic patients with different glycaemic state: diabetes, impaired, or normal fasting glucose. Although there was an association between large epicardial adipose tissue volume and CAD, it was not independent of traditional risk factors that seemed to outweigh epicardial fat as a risk factor for CAD. On the contrary, Ito et al.32 found in patients undergoing percutaneous coronary interventions that large epicardial fat volume was associated with ACS and the presence of the thin cap fibroatheroma phenotype by OCT.

Advanced imaging techniques

Three-dimensional echocardiography

The advantages of the 3D in echocardiography have been pointed out in several papers published in 2012. First, Lang et al.33 have produced, with the help of an outstanding writing committee, the joint EAE/ASE recommendations paper for image acquisition and display using 3D echocardiography. Three-dimensional echocardiography has gained the value in the evaluation of LV volumes and function, cardiac mechanics, valve morphology and function, and cardiac chambers structure. In a large meta-analysis, Kleijn et al.34 underlined that the 3D echocardiography is a feasible and reliable tool for the assessment of LVD and may have an additional value to the current selection criteria for accurate prediction of response to CRT. In another study, the same authors reported the reliability of LV volumes and function measurements using 3D speckle tracking echocardiography (3DSTE). Reliability was not only good, but also even better for circumferential strain, a parameter for which the inter-observer variability is known to be high with 2D echocardiography.35 When compared with CMR, 3DSTE-derived LV volumes were underestimated in most patients, while the measurement of the LVEF revealed excellent accuracy. Measurements of circumferential strain were systematically greater (i.e. more negative) with 3DSTE than CMR, which likely reflects various inter-technique differences that preclude direct comparability of their measurements.36 Underestimation of LV volumes and EF by 3D echocardiography was also pointed out by Miller et al.37 They showed, however, that the degree of underestimation was also partly related to suboptimal echocardiographic image quality.

The decline in right ventricular (RV) EF in relation to progressive RV remodelling is a predictor of clinical worsening in patients with pulmonary arterial hypertension (PAH). Grapsa et al.38 performed a longitudinal follow-up of patients with PAH using 3D TTE. They confirmed that PAH leads to right atrial (RA) and RV dilatation and functional deterioration, which are linked to an adverse clinical outcome. In that study, 3D measurement of RA sphericity index emerged as the most sensitive parameter to predict the outcome.

The tricuspid valve annulus (TA) is a complex 3D structure that is incompletely understood. In 50 cases (20 controls and 30 patients with dilated right heart), Ring et al.39 reported the added value of 3D transesophageal echocardiography (TEE) for the detailed evaluation of TA. They showed that, in dilated right hearts, the TA dilates in a septo-lateral direction, resulting in a more circular orifice. The dynamic changes of the TA are lost in these patients, potentially contributing to functional tricuspid regurgitation.

Similar to TA, mitral annulus geometry can be accurately evaluated by 3D TEE. Using 3D TEE as the reference method, Hyodo et al.40 pointed out that conventional antero-posterior/commissure-commissure mitral annulus diameter measurements are sufficiently correlated to 3D planimetry of the mitral annulus to be recommended in practice.

In a review paper, Muraru et al.41 smartly described the role and the incremental clinical benefits of 3D vs. 2D echocardiography in the assessment of the functional anatomy of the aortic valve complex.

RV outflow tract (RVOT) pacing has been advocated as an alternative to apical pacing to avoid long-term detrimental effects. RVOT has a complex geometry limiting the identification of the pacing site by standard X-ray. Gao et al.42 showed how helpful is 3D TTE for the visualization of the RVOT high septal pacing site. Of note, although it is well known that RV pacing has a negative impact on global LV function, its mechanism remains unclear. In 116 RV paced patients, Tanaka et al.43 described the usefulness of 3DSTE for the evaluation of early subtle changes in multidirectional regional RV deformation associated with chronic RV pacing, which may play a clinical role in predicting future global LV dysfunction.

Contrast echocardiography

Myocardial contrast echocardiography (MCE) is a remarkable technique that allows immediate simultaneous assessment at the bedside of wall motion, LV opacification, and myocardial perfusion. The clinical usefulness of MCE has been highlighted in a couple of articles. Galiuto et al.44 evaluated the anatomical correlates of PD MCE in the subacute phase of AMI. The authors demonstrated that both coronary microcirculation and myocardial cells within PD areas are anatomically damaged in AMI.

Regadenoson is a novel selective A2A receptor agonist, comparable with adenosine. Le et al.45 examined the haemodynamic profile and ability of regadenoson to detect coronary artery stenosis during MCE in an open chest animal model of dogs. They showed that regadenoson increased the coronary blood flow significantly for 30 min, which was attenuated in proportion to coronary stenosis severity. The optimum time for image acquisition was 3–10 min after drug administration.

Kutty et al.46 evaluated the efficacy of MCE in the haemodynamic and anatomic assessment of repaired congenital heart disease (CHD) at rest and during supine bicycle stress echocardiography. Fifty-one CHD patients with compromized image quality were prospectively studied at rest and during exercise using definity and contrast pulse sequencing. The authors pointed out that MCE at rest and during supine exercise echocardiography enabled safe and comprehensive assessment of anatomy, haemodynamics, and biventricular functional and perfusion reserve in adolescents and young adults with surgically modified CHD.

New techniques

Integrated backscatter has become a technique for the assessment of myocardial fibrosis. Kosmala et al.47 compared the association cardiac function with markers of fibrosis in 172 patients with metabolic syndrome. They found that myocardial echodensity by integrated backscatter was a stronger correlate of LV systolic and diastolic dysfunction in MS, than circulating pro-collagen peptides. They further concluded that an echocardiographic evaluation of myocardial acoustic properties might have clinical utility in MS and other disease conditions associated with enhanced fibrosis. This paper was accompanied by an editorial by Bijnens and D'hooge48 who elaborated the challenges and the potential use of the integrated backscatter technique.

A promising new technique for exploring flow patterns in LV is echocardiographic particle image velocimetry. This technique was studied by Gao et al.49 and concluded that contrast-enhanced imaging of blood flow dynamics can be used to characterize flow patterns inside the LV with acceptable accuracy.


In its first year as a multi-modality cardiovascular imaging journal, the European Heart JournalCardiovascular Imaging has published an impressive collection of review articles and original studies using all major imaging modalities and covering a wide spectrum of methods and clinical topics. This review has summarized the studies in myocardial function, myocardial ischaemia, and emerging techniques published in 2012. Part II of the review will focus on valvular heart diseases, heart failure, cardiomyopathies, and CHDs.

Conflicts of interest: none declared.


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