Heart failure (HF) is a complex and progressive disease that leads to significant morbidity and mortality. Approximately 1-2% of the adult population in developed countries has HF, the prevalence rising to ≥10% among persons aged 70 years or older.1 There are many causes of HF, and these vary in different parts of the world. However, the etiology is routinely categorized as ischemic or non-ischemic.

Patients with ischemic HF may benefit from revascularization2 and so the presence, anatomic characteristics, and functional significance of coronary artery disease (CAD) should be assessed in patients with new-onset HF.3

The gold standard diagnostic method for CAD detection has been invasive coronary angiography (ICA). Multidetector computed tomography (MDCT) has emerged as a robust alternative, demonstrating high diagnostic performance for identifying coronary stenosis.4 Several recent studies5–8 have shown that it is extremely accurate even in subjects with left ventricular (LV) dysfunction. Therefore, new-onset HF is currently considered an appropriate indication for MDCT.9 However, the performance of coronary MDCT angiography (CTA) for the differentiation of HF etiology in clinical practice has not been fully validated, and few studies have set out to evaluate the role of coronary artery calcium (CAC) score and CTA in patients with LV dysfunction. We sought to assess the value of MDCT in the exclusion of ischemic etiology in HF patients and to test the potential application of the Agatston score as a gatekeeper for CTA in this context.

Of the 4424 patients who underwent CTA between April 2006 and May 2013, 100 fulfilled the study's inclusion criteria. Patient data are presented in Table 1.

Diagnostic quality of CTA was classified as good in 67% of patients, average in 25% and poor in 8%.

According to the MDCT findings, 27 patients presented obstructive CAD: 11 with ≥50% luminal stenosis and 16 with CAC >400 (Figure 1).

Figure 1.

Cardiomyopathy etiology of the 100 HF patients who underwent CTA. CAD: coronary artery disease; CTA: multidetector computed tomography coronary angiography; ICA: invasive coronary angiography; MDCT: multidetector computed tomography.

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Patients with obstructive CAD presented lower body mass index (25.1 vs. 27.7 kg/m2, p=0.01), less radiation exposure (following the study protocol) (0.9 vs. 5.5 mSv, p=0.005) and lower LVEF (31 vs. 37%, p=0.004).

All patients with obstructive CAD as assessed by CTA had some degree of calcification (CAC >0) and the patient with the lowest calcium score in this group had a value of 3.3.

Of the 27 patients with CAD as assessed by MDCT, 21 underwent ICA (nine with CAD according to CTA and 12 with Agatston calcium score >400). Six patients with CAD detected on MDCT did not undergo ICA. Of these, two were referred for non-invasive stress perfusion imaging and ischemia was excluded. In the other four patients the physician's decision was to correct cardiovascular risk factors and to optimize therapy without further testing.

Of the 21 patients who underwent ICA, 12 had non-obstructive CAD and nine (43%) had obstructive CAD. Of these only six (29%) had criteria for ischemic cardiomyopathy (Table 2).

Of the seven patients in atrial fibrillation (AF), one had tachycardia precluding CTA acquisition and only underwent CAC testing. Of the remaining six, three had no CAD, one had ≥50% stenosis on CTA and two had CAC >400. Average image quality was reported in all of these CTA cases. The patient with rapid heart rate and the patients with obstructive CAD and CAC >400 underwent ICA, which revealed no obstructive CAD.

The main finding of our study is that in symptomatic heart failure patients with depressed LV function of unknown etiology, MDCT was able to exclude CAD in the majority of cases (73%). Furthermore, in our intermediate to low pre-test probability HF population, the absence of coronary calcification was an effective predictor of the absence of CAD and was thus able to confidently exclude an ischemic etiology. According to these findings, a calcium score threshold of zero can be safely used as a gatekeeper for CTA acquisition in these patients – thus avoiding the small, but non-negligible, risk of complications related to contrast administration and radiation exposure.

Our results are in line with the published literature.18 Abunassar et al. reported that in a population of 153 patients with a history of HF and low LVEF (<50%) all the 13 subjects with ischemic etiology had some degree of coronary calcification as assessed by the calcium score, whereas 30% of the subjects with non-ischemic cardiomyopathy had a Agatston score of zero.18

CAD is believed to be the underlying cause in approximately two-thirds of patients with HF and low LVEF.19,20 The distinction between ischemic and non-ischemic cardiomyopathy and assessment of CAD extent have major clinical implications in patients with dilated cardiomyopathy.21 Clinical data and assessment of pre-test probability based on cardiovascular risk factors have been shown to be unreliable in this differentiation.21,22 Therefore, auxiliary exams are usually necessary. One approach would be the use of functional tests to detect ischemia scar, using nuclear, magnetic resonance or stress echocardiography. Cardiac magnetic resonance (CMR) may be particularly suited for this indication, given its accurate assessment of volumes and biventricular function and its high-resolution ability to detect scarring and to distinguish different patterns of fibrosis according to the underlying etiology. However, the availability of CMR is still limited in some centers and a significant proportion of HF patients are still referred for ICA to assess the coronary tree and to infer the etiology. A recent study demonstrated that nearly two-thirds of patients referred for ICA do not have obstructive CAD (defined as ≥50% stenosis in the left main or ≥70% in any other coronary artery).23 According to this study, ICA may be unnecessary in many patients – and MDCT might be used as an effective non-invasive alternative for the exclusion of CAD.24–26 However, HF patients have distinctive characteristics that may limit the image quality and diagnostic performance of MDCT, particularly reduced apnea capability, higher prevalence of atrial fibrillation and lower cardiac output (which tends to slow the first passage of contrast, leading to contrast dilution and suboptimal vessel opacification). In our study, MDCT image quality was considered diagnostic in the majority of patients and overall performance appears to support its use for exclusion of CAD in this context.

Only a third of patients presented obstructive CAD on CTA, and only 6% had criteria for ICM. This low prevalence of CAD may be explained by the study design, since patients referred for MDCT are usually those with a relatively low probability of CAD. In our study the majority of patients had a low to intermediate pre-test probability, probably reflecting a good clinical selection of candidates for this test, especially suited for the exclusion of CAD.

One particular subgroup of HF patients requiring a focused analysis is the population with AF.27 The reported prevalence of AF in modern heart failure series ranges from 13% to 27%. Moreover, the prevalence of AF in patients with HF increases in parallel with disease severity, ranging from 5% in patients with mild HF to 10%–26% among patients with moderate HF and up to 50% in patients with severe HF.27 In our HF population, with a mean LVEF of 35±7.7%, only 7% of patients presented AF. This low prevalence may be explained, once again, by patient selection. Although AF poses a challenge to MDCT due to typically higher rates and an irregular R-R interval,25 recent studies28,29 have demonstrated that MDCT can still be an option in this context. Also, Marwan et al.30 reported that in 60 patients (15% with unexplained LV dysfunction) with controlled AF (range 32-107 bpm) referred for MDCT for exclusion of CAD the sensitivity, specificity, positive predictive value and negative predictive value were 100%, 85%, 67% and 100%, respectively. Our data, although on only seven AF patients, are consistent with these findings.

In our intermediate to low pre-test probability HF population, MCDT was able to exclude an ischemic etiology in 73% of cases in a single test. According to our results the Agatston calcium score can serve as a gatekeeper for CTA in patients with HF.

The authors have no conflicts of interest to declare.

PAS, NB, NDF, MC, DL and WF performed the CTA. NDF performed the statistical analysis. NB was a major contributor in writing the manuscript. All authors read and approved the final manuscript.