Current Cardiovascular Imaging Reports

, Volume 4, Issue 2, pp 98–107

Measuring Treatment Effects in Clinical Trials Using Cardiac MRI


    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Georg Fuernau
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Ingo Eitel
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Philipp Lurz
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Steffen Desch
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Gerhard Schuler
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center
  • Holger Thiele
    • Department of Internal Medicine/CardiologyUniversity of Leipzig – Heart Center

DOI: 10.1007/s12410-011-9069-5

Cite this article as:
de Waha, S., Fuernau, G., Eitel, I. et al. Curr Cardiovasc Imaging Rep (2011) 4: 98. doi:10.1007/s12410-011-9069-5


Cardiac MRI (CMR) offers the potential to assess valid and reliable parameters associated with cardiac diseases and the corresponding clinical prognosis. It has therefore emerged as a tool for outcome measures, resulting in lower study sample sizes, shorter duration of clinical studies, and subsequently less trial costs. This review focuses on the theoretical and practical background of CMR in measuring treatment effects in clinical trials.


Cardiac magnetic resonance imagingClinical trialsOutcome measures


The goal of clinical research identifying new therapeutic strategies is to reduce mortality and morbidity by altering the natural course of disease. The selection of appropriate end points in clinical trials is of crucial importance in the assessment of the effects of therapeutic interventions. Meaningful end points should 1) link the treatment effect to the underlying pathophysiology; 2) be clinically relevant and provide prognostic information to subsequent patient outcome; and 3) be determined accurately, with high specificity and sensitivity, as well as high reproducibility. Moreover, the choice of the primary end point influences the size of the projected treatment effect, which is a major determinant of study sample size [1••].

Cardiac MRI (CMR) provides a multifaceted view of the heart by assessing cardiac function and structure in vivo and noninvasively. CMR parameters have been linked to specific cardiac pathophysiological states and can be assessed with high intraobserver and interobserver reproducibility [2•]. Several CMR parameters have been linked to adverse clinical outcome in a diversity of cardiac diseases [3•]. Therefore, CMR offers the potential to assess clinical prognosis and therapeutic success, resulting in lower study sample sizes, shorter duration of clinical studies, and less trial costs. Consequently, CMR has emerged as an important tool for outcome measurements.

This review focuses on the role of CMR in measuring treatment effects in clinical trials. We will discuss the level of evidence and report on data from recent studies.

Statistical Background: Primary End Point, Treatment Target Effect, and Study Sample Size

Primary End Point

Clinical trial end points used to assess treatment effects should be causally linked to the underlying pathology [4]. However, some end points might be directly linked to the pathophysiological elements but nonetheless not influence mortality or morbidity [5]. Therefore, an end point should also be related to the patient’s clinical outcome. Furthermore, an ideal end point should be easy to measure and demonstrate high intraobserver and interobserver reproducibility, partly influencing sensitivity and specificity [1••].

Treatment Effect

The basis for the definition of the target treatment effect is the “minimum clinically important difference” of measures leading to the subsequent minimum change in an end point a trial is designed to detect [6]. It is often defined by clinical judgment, based on current literature and guidelines or expert consensus. In cardiovascular medicine, clinical parameters such as death, myocardial infarction, or new congestive heart failure are often being used as primary end points, reflecting mortality and morbidity. The incidence of “hard” clinical end points is often relatively low, and long follow-up periods or large study sample sizes are required to detect treatment effects (e.g. reduction in mortality). Thus, surrogate parameters known to correspond with clinical outcome are often used as alternative end points to assess the effect of a new therapeutic strategy.

Statistical Power and Study Sample Size

For a superiority trial with a continuous surrogate end point, sample size is based on the effect size (the expected absolute difference between treatment groups), its variability, and the alpha and beta levels set by the study design [7]. By convention, alpha and beta are usually fixed. However, by choosing an appropriate surrogate end point it is often possible to detect small effect sizes, thus leading to significant reductions in study sample sizes and an increase in statistical power.

Cardiac Magnetic Resonance

CMR can offer appropriate study end points as 1) it allows direct visualization of the heart, including assessment of its function, structure, and tissue characteristics which are directly linked to different pathological states (Table 1) [2, 8]; 2) various CMR parameters have been shown to be associated with adverse prognosis and thus offer valid data [3•]; 3) many CMR parameters show low intraobserver and interobserver variability and high reproducibility, offering reliable data; and 4) changes in CMR parameters often occur more frequently and earlier after the therapeutic intervention than most clinical events. Thus, the use of CMR as outcome measure in clinical trials often allows the reduction of a study’s sample size. Several clinical trials have utilized CMR as an outcome measure. While an in-depth discussion of CMR-pathological correlation is beyond the scope of this paper, selected recent trials will be reviewed to enlighten the role of CMR in measuring treatment outcomes. A detailed list of published and ongoing trials using CMR parameters as outcome measures can be found in Table 2.
Table 1

Assessment of cardiac function, structure, and tissue characterization using cardiac MRI



Clinical indications


SE and double IR GRE/SSFP

- LV/RV/LA/RA dimensions

- Anatomy

- Myocardial masses



- LV/RV/LA/RA volumes

- Ejection fraction

- Wall motion abnormalities (at rest + during stress)

- Valvular heart disease


T1-sensitive sequences

- Ischemia evaluation, detection of functionally significant stenoses

Tissue characterization


- Cardiac mass


- Acute myocardial infarction


- Acute myocarditis/inflammation


- Iron overload cardiomyopathy


- Myocardial infarction (acute + chronic)


- Myocarditis


- Amyloidosis


- Sarcoidosis


- Hypertrophic cardiomyopathy

GRE, gradient echo; IR, inversion recovery; LA, left atrial; LGE, late gadolinium enhancement; LV, left ventricular; RA, right atrial; RV, right ventricular; SE, spin echo; SSFP, steady-state free precession

Table 2

Recent randomized clinical trials using CMR parameters as primary or secondary outcome measures



Sample size

CMR end point

Year published

Volumes and function

Jahnke et al. [17]

Pulmonary vein isolation in atrial fibrillation


LA volumes


Gaddam et al. [50]

Spironolactone in patients with resistant hypertension and hyperaldosteronism


LV volumes and LV mass at 3 and 6 months


Cowan et al. [14] (ONTARGET CMR substudy)

Combination of telmisartan and ramipril vs ramipril alone in high-risk CAD patients


LV mass and volumes at 24 months


Stable CAD

Kirschbaum et al. [51]

Complete vs incomplete revascularization in multivessel CAD


LV ejection fraction at 6 months


Chan et al. [23]

Endomyocardial implantation of autologous bone marrow cells in patients with severe CAD


LV ejection fraction and myocardial perfusion reserve at 6 months


Thiele et al. [12] (EPACCO trial)

Application of circulating progenitor cells in CTO


LGE and LV ejection fraction at 3 and 15 months


Pegg et al. [52]

Comparison of a hybrid technique on-pump beating heart CABG with conventional on-pump CABG in patients with CAD


LGE, LV ejection fraction, and LV volumes at 6 months


Yao et al. [53]

Intracoronary administration of bone marrow mononuclear cells in chronic myocardial infarction


LV ejection fraction and LV volumes at 6 months


Pegg et al. [54]

Off-pump CABG vs on-pump CABG in patients with CAD and CHF


RV ejection fraction and RV volumes at 6 months


Webb et al. [55]

Oral testosterone in men with low plasma testosterone and CAD


Myocardial perfusion reserve at 2 months


Cheng et al. [56]

PCI vs conservative treatment in CTO and nonoccluded CAD


Myocardial perfusion reserve at 2 months


Acute myocardial infarction

Thiele et al. [37] (LIPSIA-N-ACC study)

High-dose N-acetylcysteine in addition to primary PCI in STEMI


Myocardial salvage index at days 2–4


Abbate et al. [57]

Interleukin-1 blockade with anakinra in STEMI


LV end-systolic volume index at 10–14 weeks


Wöhrle et al. [58]

Autologous intracoronary bone marrow cell therapy after STEMI


LV ejection fraction at 6 months


Lonborg et al. [36]

Ischemic postconditioning in STEMI


Myocardial salvage at 3 months


Haeck et al. [59]

Proximal embolic protection and thrombus aspiration in STEMI


Infarct size at 4–6 months


Patel et al. [60] (APEX-AMI trial)

Pexelizumab (anti-C5 complement antibody) in STEMI


Infarct size and LV ejection fraction at 90 days


Weir et al. [61]

Eplerenone in CHF after STEMI


LV end-systolic volume index at 24 weeks


Dill et al. [11] (REPAIR-AMI trial)

Intracoronary administration of bone marrow–derived progenitor cells after STEMI


LV ejection fraction at 4 and 12 months


Tendera et al. [62] (REGENT study)

Intracoronary infusion of bone marrow–derived selected CD34 + CXCR4+ cells vs non-selected mononuclear cells after STEMI


LV ejection fraction at 6 months


Song et al. [63]

Upstream high-dose tirofiban treatment in STEMI


Infarct size at 1 month


Atar et al. [30] (FIRE study)

Administration of FX06 in AMI


Infarct size at 5 days


Sardella et al. [32] (EXPIRA trial)

Thrombus aspiration in STEMI


Microvascular obstruction at 4 days and infarct size at 3 months


Thiele et al. [29] (LIPSIAbciximab)

Intracoronary vs intravenous bolus abciximab application in patients with STEMI


Infarct size and microvascular obstruction at 2 days


Hahn et al. [64]

Distal protection device in STEMI


Infarct size at 3 days


Engelmann et al. [65]

Granulocyte colony-stimulating factor in subacute STEMI


Global and regional myocardial function at 3 months


Kang et al. [66] (MAGIC Cell-3-DES trial)

Intracoronary infusion of mobilized peripheral blood stem cells in STEMI


LV ejection fraction at 6 months


Ripa et al. [67] (STEMMI trial)

Granulocyte colony-stimulating factor after STEMI


Systolic wall thickening at 6 months


Janssens et al. [68]

Transfer of autologous bone marrow–derived stem cells after STEMI


LV ejection fraction at 4 months


Thiele et al. [69]

Pre-hospital combination-fibrinolysis plus conventional care vs pre-hospital combination-fibrinolysis plus facilitated PCI in STEMI


Infarct size at 6 months


Gick et al. [70]

Filter-based distal protection in STEMI


Infarct size at 3 days


Wollert et al. [71] (BOOST trial)

Intracoronary transfer of autologous bone marrow cells after STEMI


LV ejection fraction at 6 months


Valvular heart disease

Kim et al. [16]

Surgery in TR


RV volumes and RV ejection fraction at 1 and 27 months


Gelfand et al. [72]

Surgery in MR


LV volumes and LV ejection fraction at 27 months


Lurz et al. [41]

Bare metal stenting and percutaneous pulmonary valve implantation for treatment of right ventricular outflow tract obstruction


RV stroke volume and pulmonary regurgitation


Nonischemic cardiomyopathies

Tanner et al. [73]

Deferoxamine monotherapy vs deferiprone and deferoxamine in patients with iron-overload cardiomyopathy


LV ejection fraction and T2* at 6 and 12 months


Hughes et al. [46]

Agalsidase in patients with Fabry disease


LV mass at 6 months


Shimada et al. [74]

Prednisolone in cardiac sarcoidosis


LGE at 1 month


CABG, coronary artery bypass graft; CAD, coronary artery disease; CHF, congestive heart failure; CTO, chronic total occlusion; LA, left atrial; LGE, late gadolinium enhancement; LV, left ventricular; MR, mitral regurgitation; PCI, percutaneous coronary intervention; RV, right ventricular; STEMI, ST-elevation myocardial infarction; TR, tricuspid regurgitation

Volumes and Function

Ventricular volumes, masses, and function can be assessed with CMR by acquisition of a three-dimensional (3D) stack of short-axis images covering the whole left and right ventricle. In comparison to other imaging techniques, such as echocardiography, assessment of cardiac function using CMR is more accurate and reproducible with lower intraobserver and interobserver variability [9].

Impaired right (RV) and left ventricular (LV) function is associated with adverse clinical outcome [10] and thus has been used repeatedly as a target of new therapeutic strategies, such as in the CMR substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial [11]. This study could demonstrate a significant improvement of LV function after 12 months through intracoronary administration of bone marrow–derived progenitor cells in 54 patients with ST-elevation myocardial infarction (STEMI) and impaired LV function. Likewise, in stable coronary artery disease (CAD) in the setting of recanalized chronic total occlusions it has been shown that application of circulating progenitor cells results in a significant improvement of LV function as compared to control at short-term and long-term follow-up [12].

LV mass and volumes are known to be influenced by different pathological states, such as arterial hypertension. In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), the combination of the angiotensin receptor blocker telmisartan with the angiotensin-converting enzyme inhibitor ramipril did not lead to a decrease in morbidity and mortality in comparison to ramipril alone [13]. In the CMR substudy including 287 patients, the combination of telmisartan and ramipril had a similar effect on LV mass and volumes than ramipril alone [14]. These results strongly support the major outcome findings and even give insight into the potential pathophysiological explanations for the results of the primary study.

Assessment of RV function using echocardiography is limited, mainly due to the complex and asymmetric shape of the right ventricle. 3D echocardiography has overcome some of these limitations, although assessment of RV function using CMR is easier to standardize, less prone to registration errors, and has better resolution than 3D echocardiography [15]. CMR was used in a study of 31 patients undergoing surgery for severe functional tricuspid regurgitation for the assessment of RV volumes. The trial could demonstrate a significant reduction in RV volumes and preserved RV function post-surgery. Furthermore, RV end-diastolic volume index before surgery could effectively discriminate between patients with post-surgical normal RV function from those with impaired RV function, enlightening the importance of accurate pre-surgical assessment of RV volumes and function [16].

Apart from RV and LV function and volumes, CMR can also assess atrial volumes. A study by Jahnke et al. [17] could demonstrate that pulmonary vein isolation for atrial fibrillation with subsequent restoration of sinus rhythm leads to a significant decrease of left atrial systolic and diastolic volumes, indicating structural reverse remodeling.

Myocardial Ischemia and Scar in Stable CAD


Assessment of myocardial ischemia using CMR can be performed with stress perfusion (Fig. 1a) or stress wall motion assessment. Both imaging techniques have shown good performance for the detection of relevant CAD in comparison to invasive coronary angiography or positron emission tomography [18, 19]. Furthermore, perfusion imaging has shown excellent sensitivity and specificity to detect functionally significant coronary stenoses in comparison to the pressure wire–derived fractional flow reserve, which represents the invasive gold standard [20]. The absence of inducible new regional wall motion abnormalities or perfusion deficiencies has been shown to be associated with a good clinical prognosis [21, 22]. Recently, Chan et al. [23] could demonstrate that direct endomyocardial implantation of autologous bone marrow cells in patients with severe stable CAD leads to a significant increase in myocardial perfusion reserve. This has also been shown in recanalized chronic total occlusions, where endothelial progenitor cell application led to a significant improvement in perfusion in comparison to placebo [12]. Nevertheless, perfusion or stress wall motion imaging have not been used in a large number of trials. This might in part be caused by the current non-standardized imaging parameters and the difficulties of quantification of the effects.
Fig. 1

a, Myocardial perfusion at rest (left) and during stress (right) displaying a perfusion deficit in the anterior and septal wall (white arrows). b, CMR findings in acute myocardial infarction. Upper left/middle/right: T1-weighted CMR showing transmural myocardial infarction (red contour) with a central core of microvascular obstruction (yellow contour). Lower left/middle/right: T2-weighted CMR showing myocardial edema (green contours) with a hypointense core indicating intramyocardial hemorrhage (blue contours)


Late gadolinium enhancement (LGE) can be assessed by T2-weighted imaging 10 to 15 min after gadolinium injection and appears as a hyperenhancement. In patients with CAD it corresponds to myocardial fibrosis and scar tissue. LGE has been shown to be associated with adverse clinical outcome in patients with suspected CAD even without clinical evidence of prior myocardial infarction and provides incremental prognostic information beyond common clinical, angiographic, and functional predictors [24]. A small clinical CMR substudy demonstrated a significant reduction of LGE in patients with stable CAD after recanalization of chronic total occlusions and application of endothelial progenitor cells as compared to controls [12].

Acute Myocardial Infarction

Using T1-weighted and T2-weighted imaging, infarct size, microvascular obstruction (MO), as well as myocardial salvage and myocardial hemorrhage can be assessed (Fig. 1b).

Infarct Size

With assessment of LGE using T1-weighted imaging it is possible to directly visualize and quantify areas of infarcted myocardium, both after STEMI and non-STEMI [25]. In an international multicenter study this technique demonstrated high diagnostic sensitivity to detect either acute or chronic infarctions [26]. Due to an in-plane spatial resolution of 2 mm leading to a fourfold to sixfold higher spatial resolution and a higher contrast-to-noise ratio than single photon emission CT, LGE imaging has shown to be consistently more sensitive and specific in detecting and quantifying the extent of infarction [27]. Furthermore, infarct size has been shown to be associated with worse functional and clinical outcome [28] and has therefore been used as a surrogate end point in various studies examining reperfusion success. In the Randomized Leipzig Immediate Percutaneous Coronary Intervention Abciximab IV Versus IC in ST-Elevation Myocardial Infarction (LIPSIAbciximab) trial including 154 patients with STEMI undergoing primary percutaneous intervention (PCI), intracoronary bolus administration of abciximab led to a significant reduction of infarct size in comparison to intravenous injection [29]. In the first multicenter study analyzing infarct size as primary end point, Atar et al. [30] could not show a significant reduction of infarct size in patients with STEMI receiving FX06, an anti-inflammatory acting peptide, in comparison to the control group. Various trials analyzing the impact of stem cell administration on infarct size during or early after reperfusion yielded conflicting results (Table 2).

Microvascular Obstruction

CMR can also display zones of MO, which appear as central dark zones within the infarcted area. MO represents myocardial tissue hypoperfusion corresponding to “no-reflow.” MO can be assessed 1 to 2 min (early MO) and 10 to 15 min (late MO) after gadolinium injection. Recently, a higher prognostic impact of late MO in comparison to early MO independent of traditional angiographic, clinical, and electrocardiographic parameters could be demonstrated [31]. In a substudy of the Thrombectomy with Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention (EXPIRA) trial, both the prevalence, as well as the extent of MO could be reduced by performance of thrombectomy prior to PCI as compared to controls [32]. These results highlight the beneficial effect of the studied therapeutic interventions and give insight into the pathophysiological mechanisms leading to the development of MO.

Myocardial Salvage

Another part of a comprehensive infarct CMR protocol is T2-weighted imaging. T2-weighted CMR sequences are ultra-sensitive to water-bound protons, delivering information on myocardial edema displayed as areas of high T2-signal. Recently, T2-weighted imaging has demonstrated high accuracy in measuring the area at risk in reperfused infarcts [33, 34]. By comparing T2-weighted imaging to LGE, myocardial salvage can be assessed retrospectively [34]. Importantly, CMR assessment of myocardial salvage can be performed by only one scan within the first week of the index event and does not require injection of an isotope as compared to nuclear scintigraphy. As a consequence, assessment of myocardial salvage has been significantly simplified by the introduction of CMR. Myocardial salvage is a strong predictor for adverse clinical outcome after STEMI [35] and has been used to test the efficacy of reperfusion modalities. In a study by Lonborg et al. [36], a significant increase in myocardial salvage through mechanical post-conditioning in patients with STEMI could be observed. In the Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate Percutaneous Coronary Intervention Acute Myocardial Infarction N-ACC (LIPSIA-N-ACC) study, the first clinical trial analyzing myocardial salvage as an end point, N-acetylcysteine, which has antioxidant properties, failed to show beneficial effects on myocardial salvage, despite encouraging results in animal models [37].

Myocardial Hemorrhage

Recent studies have also demonstrated the potential of T2-weighted imaging to detect intramyocardial hemorrhage (IMH), a marker of severe reperfusion injury. A hypointense core within the hyperintense area at risk likely corresponds to such IMH. IMH has been shown to be an independent predictor of adverse LV remodelling irrespective of the initial infarct size and MO [38]. However, histological proof of the specificity of hypointense cores in T2-weighted images (vs more specific T2*-weighted CMR) is still awaited. These remaining questions need to be clarified before the use of IMH in clinical trials can be recommended.

Valvular Heart Disease

Echocardiography represents the gold-standard for valvular morphological assessment and grading of severity of valvular stenosis and/or regurgitation. However, there is an increasing role of CMR regarding timing and assessment of outcome of valvular interventions. Only very limited data are available on valvular interventions and the impact on mortality, both for surgical and transcatheter interventions. Procedural success is most often based on ventricular functional and morphological remodeling. Given its high accuracy in the assessment of ventricular volumes and ejection fraction, CMR has been used to measure the impact of aortic valve replacement in the context of aortic regurgitation and stenosis on LV systolic and diastolic function [39]. Further, CMR plays a major role in clinical trials on timing and outcome of right-sided valvular lesions. Especially in patients with congenital heart disease and pulmonary regurgitation or stenosis, the exact timing for interventions is still unknown and fiercely debated. In recent studies, RV end-diastolic volume thresholds, as assessed by CMR, have been established, beyond which normalization of RV volumes after pulmonary valve replacement is unlikely [40]. Finally, with the extension of minimal invasive and transcatheter valve interventions, the techniques and the patient population undergoing treatment will change fundamentally. CMR is likely to be the key technique to assess the impact of these new techniques on biventricular remodeling [41].

Nonischemic Cardiomyopathies

Using cine-weighted and T2-weighted imaging, as well as LGE, further distinction between different entities of cardiomyopathies can be performed. The main focus is on the differentiation between ischemic or nonischemic origin. Nonischemic cardiomyopathies often display typical patterns in MRI.

Iron overload cardiomyopathy can be directly visualized using T2* imaging. T2* times have been shown to be inversely related to the amount of iron deposition and are associated with adverse clinical prognosis [42]. In a study by Modell et al. [43], CMR-guided iron chelate treatment led to a significant decrease in mortality by identifying patients at the highest risk, leading to intensification of medical therapy.

In dilated cardiomyopathy LGE typically occurs mid-wall, particularly affecting the basal and mid-septum. Currently, LV ejection fraction is widely used to determine the need for an implantable cardioverter-defibrillator (ICD). In trials with limited patient numbers it has been shown that the amount of LGE is a stronger predictor for cardiac death and inducible arrhythmias than LV ejection fraction [44]. These findings offer the potential for further risk stratification in patients with an LV ejection fraction >35%, although this has not been evaluated in a large study cohort so far.

A similar relation of LGE with sudden cardiac death was observed in patients with hypertrophic cardiomyopathy >40 years of age [45]. However, no data exist using LGE to guide ICD implantation.

In Fabry disease, a condition in which α-galactosidase activity is reduced leading to an accumulation of glycosphingolipid GB3, midwall LGE of the basal lateral wall, as well as prominent LV hypertrophy can be observed. In a study by Hughes et al. [46], a significant decrease in LV mass could be demonstrated in patients receiving enzyme replacement therapy in comparison to the placebo group, which was consistent with other laboratory and electrocardiographic findings.

In patients with sarcoidosis, cardiac involvement is usually patchy and affects mainly the LV, resulting in low accuracy of endomyocardial biopsies due to sampling errors. In contrast, CMR can detect the often bizarre patterns of LGE and demonstrate areas of inflammation using T2-weighted imaging. This allows early identification of cardiac manifestations leading to an early initiation of corticosteroid therapy, which is supported by the findings of Vignaux et al. [47].

In suspected myocarditis, CMR can be understood as the first-line imaging technique [48]. However, to date no therapeutic intervention other than symptomatic or unspecific treatment has shown significant improvement in clinical outcome or a change in the corresponding CMR findings. However, this is currently part of extensive clinical research, and CMR parameters might help identify beneficial effects of a treatment earlier than clinical outcome parameters.

In patients following heart transplantation, organ rejection can be assessed with the techniques used for the detection of myocarditis [49]. This is of importance as screening for organ rejection is a critical component of care in post-transplantation patients. Although up to date endomyocardial biopsies are the standard screening tool, CMR might possibly reduce or eliminate the need for endomyocardial biopsies and be of importance for future studies analyzing new treatment strategies to prevent or reverse organ rejection.


With the introduction of CMR parameters as surrogate end points in clinical trials it is possible to assess biologically plausible and reliable data with high prognostic impact often occurring earlier and more frequently than the corresponding clinical outcome measures. This leads to a reduction of the projected follow-up durations as well as study sample sizes. Therefore, CMR is likely to play an important role in future clinical trials.


Drs. de Waha and Fuernau contributed equally to this work.


No potential conflicts of interest relevant to this article were reported.

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