Impact of arrhythmia on diagnostic performance of adenosine stress CMR in patients with suspected or known coronary artery disease

To the best of our knowledge, this is the first study evaluating the diagnostic performance
of adenosine stress CMR for detection of significant coronary stenosis in patients
with different types of arrhythmia. Our data indicate that adenosine stress CMR performs
well for detection of relevant coronary stenosis in patients with suspected CAD (diagnostic
accuracy 75 %), and also in patients with known CAD (diagnostic accuracy 74 %), despite
the presence of various arrhythmias during the CMR procedure. These results underscore
the increasing value of adenosine stress CMR in the real world clinical routine.

Patient characteristics

The average patient age and gender distribution are similar to previous stress CMR
studies in which patients with arrhythmia where usually excluded from analysis 5]. This also holds true for the clinical symptoms leading to CMR referral in the present
population 25]. Types of arrhythmia found in our patients include atrial fibrillation, frequent
VES and frequent SVES, which are known to be associated with CAD 8]–10]. As to expect, the subgroup with known CAD was older (72.2?±?9.6 years), with fewer
females (18 %) and higher prevalence of hyperlipidemia than the group with suspected
CAD (69.9?±?10.4 years, p?=?0.17; 54 % females, p??0.05).

General CMR findings

Median LV-EF of all patients was 54 %, which is comparable to other studies evaluating
the diagnostic performance of adenosine stress CMR in a mixed patient population comprising
patients with suspected and known CAD 23]. Patients with known CAD had a lower LV-EF and larger end-diastolic and end-systolic
volumes, most likely explained by the higher prevalence of ischemic scar represented
by CAD-type LGE (68 vs. 21 % in the suspected CAD group), resulting in reduced LV-EF
and ventricular remodeling. Ischemia was also more common in patients with known CAD
than in the group with suspected CAD, respectively.

Diagnostic performance of CMR

Entire population

Looking at the entire population, the diagnostic accuracy of stress CMR for the detection
of ?70 % stenosis on coronary angiography was 73 % (sensitivity 72 %, specificity
76 %) for all 159 patients with suspected or known CAD, and different types of arrhythmia.
This is lower than reported in a large meta-analysis 5] calculating a sensitivity of 90 % and a specificity of 81 %. However, many studies
of this meta-analysis excluded patients with arrhythmia to improve image quality,
which most likely explains the difference to our data based on patients presenting
with arrhythmia only.

Analyzing our entire population data per coronary territory demonstrate CMR to yield
a diagnostic accuracy of 77 % for the LCA (sensitivity 78 %, specificity 77 %), and
of 82 % for the RCA (sensitivity 63 %, specificity 88 %). This is also lower than
in the meta-analysis mentioned above, demonstrating sensitivities of 83, 76 and 78 %
and specificities of 83, 87, and 87 % for LAD, LCX and RCA, respectively. However,
patients with arrhythmias were excluded in most studies of this meta-analysis 5].

Comparing patients with atrial fibrillation to patients with VES (Table 3) reveals a good diagnostic accuracy for LCA and RCA (78 and 81 %) in the atrial fibrillation
group, and in patients with VES (78 and 85 %). However, the sensitivities for detecting
relevant RCA stenosis were lower in both groups when compared to the LCA (atrial fibrillation
63 vs. 81 %, VES 65 vs. 75 %). This is in accordance with other studies 5], reporting a higher sensitivity for detection of stenosis in the LAD when compared
to LCX and RCA, most likely due to the surface radiofrequency coil receiving lower
signal intensities from the inferior and lateral segments 5].

Patients with suspected CAD

Evaluating the subgroup presenting for work-up of suspected CAD the diagnostic accuracy
was 75 % (sensitivity 80 %, specificity 74 %). This is less than reported by Klem
et al. 18], who first described the Duke algorithm for work-up of suspected CAD by combining
LGE and perfusion sequences in 92 patients. However, in contrast to the present data,
the Klem population only included one patient with atrial fibrillation and two patients
with VES.

Among our 72 patients with suspected CAD the prevalence of significant coronary stenosis
was low (14 %), underscoring the need of noninvasive imaging in patients with arrhythmia
before undergoing coronary angiography. One reason for the low prevalence of CAD might
be that patients with arrhythmia are at an “increased risk” to be referred to coronary
angiography due to previous inconclusive exercise tests, or the presence of arrhythmia
itself in combination with risk factors and complaints. Interestingly, this finding
nicely matches the results of Smit et al. who performed a myocardial perfusion single
photon emission computed tomography (SPECT) analysis in patients with atrial fibrillation
and suspected CAD. The prevalence of CAD (?70 % stenosis) in this group was 13 % 26].

In a per coronary territory analysis, the diagnostic accuracy for the LCA was 76 %
(sensitivity 80 %, specificity 76 %). For the RCA our data revealed a diagnostic accuracy
of 89 % (sensitivity 100 %, specificity 89 %), completely in line with the results
of Klem et al. 18]. However, it must be noted that only one patient with suspected CAD had ?70 % RCA
stenosis.

Patients with known CAD

Focusing on the subgroup with known CAD the diagnostic accuracy of CMR stress testing
for the detection of ?70 % stenosis was 74 % (sensitivity 71 %, specificity 79 %).
A study by Klein et al. investigated the diagnostic performance of adenosine perfusion
CMR in 78 patients 27] reporting a diagnostic accuracy of 82 % for detection of ?50 % stenosis (sensitivity
77 %, specificity 90 %), excluding patients with atrial fibrillation.

Per coronary territory the diagnostic accuracy for the LCA was 78 and 77 % for the
RCA, which is also quite in line with other reports 23], 27]. Figure 4 demonstrates the feasibility of adenosine stress CMR in a patient presenting with
frequent VES (bigeminus).

Fig. 4. Two CMR exams with two different rhythms in one and the same patient. 77-year old
male undergoing stress CMR two times within four weeks due to LAD in-stent restenosis
early after intervention. One scan was performed during bigeminus (upper row), whereas the second scan was performed in sinus rhythm (bottom row). Note that the stress perfusion defect in the LAD territory (left column) could be detected in sinus rhythm, as well as during bigeminus

Limitations

Limitations of the present study are, that adenosine stress CMR was compared with
invasive coronary angiography, which is not the perfect gold standard for comparison
as functional significance of coronary obstruction and luminal diameter stenosis are
known to show only moderate correlation. Furthermore, it is important to keep in mind
that the algorithm used for CMR analysis of patients with suspected CAD is intended
to detect significant obstruction of the epicardial coronaries compared to invasive
coronary angiography (70 % stenosis). Thus, perfusion defects that were considered
as artifacts according to the algorithm used in this analysis may be a surrogate parameter
for microvascular dysfunction. Hence, it might be possible that these patients who
suffer partly from distinct anginal symptoms were classified as healthy by CMR, which
could be confirmed by coronary angiography. Another limitation is the selection bias
introduced by excluding patients with collateralized occlusions and CMR studies with
severe breathing artifacts. Despite introducing a bias, we believe that the exclusion
of collateralized occlusions is favorable in order to keep the data consistent, since
in those cases no ischemia may be present despite occlusion of the vessel. Furthermore,
removal of CMR data sets due to severe breathing artifacts seems reasonable since
aim of our study was to evaluate the impact of arrhythmia (and not of severe breathing
artifacts) on the diagnostic accuracy of an adenosine stress CMR test. Moreover, it
should be stated that only a few patients (4 out of 163 patients, =0.02 %) were excluded
due to severe breathing artifacts.

Clinical implications

On the basis of the data presented it may be safe to assume that the diagnostic performance
of adenosine stress CMR for detection of significant coronary stenosis is somewhat
impaired in patients presenting with arrhythmias compared to patients without arrhythmias
(75 vs. 88 % for suspected CAD 18] and 74 vs. 82 % in known CAD 27]), but still sufficient for clinical routine use. In fact, with a sensitivity of 72 %,
and specificity of 76 % (overall diagnostic accuracy of 73 %) adenosine stress CMR
in patients with arrhythmias performs well in comparison to other stress testing modalities
(SPECT: sensitivity 73–92 %, specificity 63–87; stress echocardiography: sensitivity
80–85 %, specificity 80–88 %; exercise ECG: sensitivity 45–50 %, specificity 85–90 %)
2], underscoring the value of adenosine stress CMR in a real world clinical setting.

Unfortunately, the current study was not designed to evaluate the prognostic value
of stress CMR in patients with arrhythmias. However, given the encouraging results
with regard to the diagnostic performance in those patients, and the results of the
EuroCMR Registry demonstrating a good prognostic value of adenosine stress CMR in
patients presenting for work-up of suspected CAD 28], including those with arrhythmias, it is likely that adenosine stress CMR also has
a good prognostic value in arrhythmic patients. Nevertheless, additional data is needed
to underscore this important point.