Ischemic CM is usually diagnosed by identifying the presence of obstructive CAD. The coronary anatomy can be assessed either directly, i.e. x-ray coronary angiography, or indirectly via stress-testing depending on the pretest probability of disease, which is derived from a combination of historical, clinical, electrocardiographic, and laboratory data. An individual with few risk factors and atypical symptoms may undergo stress testing (or simple reassurance if the risk is deemed particularly low), whereas a different individual with multiple risk factors and classic symptoms of angina may proceed directly to the catheterization laboratory. Likewise, the broad diagnosis of nonischemic CM is usually also made by assessing the coronary anatomy, either directly or indirectly. Once significant CAD has been excluded, a comprehensive evaluation including possibly endomyocardial biopsy may allow a specific etiology to be determined.
However, there are several drawbacks to the traditional approach. For one, it appears that many patients do not undergo definitive testing (invasive coronary angiography), and the accuracy of diagnosing CAD indirectly is only moderate. Autopsy data from patients enrolled in the ATLAS (Assessment of Treatment with Lisinopril and Survival) Trial13
, a large multicenter randomized trial of patients with moderate to severe heart failure, underscores this concern. Of the 171 patients who had autopsy, 70% (n=120) were diagnosed in life as having ischemic CM and 30% (n=51) as having nonischemic CM. Autopsy documented that 17% of those diagnosed with ischemic CM did not have CAD whereas 31% of those diagnosed with nonischemic CM had significant CAD. Overall, 21% had an incorrect clinical diagnosis.
One possible reason for the high rate of misdiagnosis may be an over reliance on certain findings from noninvasive imaging. Initially, it was thought that ventricular dysfunction due to nonischemic CM was primarily global rather than segmental as in ischemic CM, and that this characteristic could be used to distinguish these disorders by echocardiography14
. However, it is now recognized that segmental wall motion abnormalities are evident in up to 60 percent of patients with non-ischemic dilated CM even when patients with left bundle branch block are excluded15
. Furthermore, it is known that radionuclide scintigraphy with either dipyridamole or exercise testing is unreliable in differentiating ischemic heart disease from nonischemic CM since both groups of patients may have evidence of reversible and fixed perfusion abnormalities16
Additionally, in cases where a specific cause of nonischemic CM is being explored, classic imaging features such as “granular sparkling” on echocardiography in cardiac amyloidosis are limited to a few rare diseases and may be less accurate than first reported. In fact, in a recent study of 196 patients clinically suspected to have cardiac amyloidosis, this finding had a sensitivity of only 26%17
. Endomyocardial biopsy, the presumed gold standard, has limitations as well. Because of sampling error, test sensitivity may be low18, 19
, and especially in the chronic setting, many patients with cardiomyopathy may show only nonspecific changes on biopsy (e.g. cell loss and fibrosis). Not surprisingly, Felker et al.6
reported that among 1230 patients that underwent endomyocardial biopsy as part of an evaluation for unexplained cardiomyopathy, a specific histologic diagnosis was provided by the biopsy in only 15% of patients.
Finally, simple distinctions between cardiomyopathies based on the presence or absence of CAD can be problematic. For instance, it is possible that a patient with nonischemic CM may also have CAD, but which is incidental and is not contributing to contractile dysfunction. The quandary is that coronary atherosclerosis is common, especially in the elderly and those with diabetes mellitus, even if patients are asymptomatic and do not have myocardial dysfunction20
. A recent study in 1,921 patients with symptomatic heart failure and LV dysfunction (LVEF <40%) undergoing diagnostic coronary angiography highlights this issue4
. Among patients with LV dysfunction “out of proportion” to their degree of CAD (i.e. those with single vessel disease), prognosis was more similar to those with nonischemic CM than the remaining group with ischemic CM. The authors concluded that even though obstructive CAD is present, those with single-vessel disease should be reclassified as nonischemic for prognostic purposes.
Another problem with the traditional approach is the inherent assumption that ischemic and nonischemic cardiomyopathy cannot coexist. However, it is plausible that both ischemic and nonischemic myopathic processes, can be present simultaneously and may be contributing independently or synergistically towards systolic dysfunction (mixed cardiomyopathy). Thus, these limitations indicate that the presence of obstructive coronary atherosclerosis is not synonymous with an ischemic etiology, and that even with objective information such as from invasive coronary angiography, the appropriate classification for a given patient is not always clear.