Normal coronary angiography: blessing or curse?

This editorial refers to ‘Changes in symptoms of anxiety and depression following diagnostic angiography: a prospective cohort study’, by T.A. Hanssen et al., on page 106. Invasive coronary angiography is the gold standard for identifying the presence or absence of obstructive atherosclerotic coronary artery disease (CAD). In the absence of obstructive CAD (i.e. no stenosis ≥50%), the patient is typically informed they have a ‘normal’ angiogram since the angiogram findings do not account for the chest pain being investigated. In patients undergoing elective angiography for the investigation of stable chest pain, approximately 60% of the angiograms are reported to be normal.1 These patients represent a heterogeneous group in relation to their presenting symptoms, possible aetiological explanations for the chest pain and prognostic outcomes. Patients with non-obstructive coronary artery disease (NoCAD) may be considered to have a very good prognosis, and typically many of these patients have only been provided with reassurance that they do not have serious cardiac disease.2 However, a number of studies have uncovered that the prognosis of patients NoCAD is not benign. This is particularly relevant for those with evidence of myocardial ischaemia,3 but also refers to an elevated risk of cardiovascular events and mortality in comparison to people without CAD.4 This begs the question, ‘what are the implications of a normal angiogram for the patient?’ Traditional medical management of CAD focuses on survival and clinical outcomes; however, these aspects do not reflect all facets of health. Patient-reported health status is the impact of disease on patient function, as interpreted by the patient.5 Health status includes the entire range of disease manifestation in a patient including symptoms, functional limitation and quality of life (Figure 1). Following the diagnosis of CAD, several factors moderate health status including changes in the levels of perceived control, and higher levels of depression and anxiety.7 Depression in particular is associated with significantly more physical limitation, and lower quality of life in patients with CAD.8 Even though invasive interventions following angiography provide effective revascularization, residual physical, or psychosocial limitation can continue to impact health status. This is exemplified in the sub-study of the COURAGE trial where over 40% of stable CAD patients receiving percutaneous coronary intervention reported on-going chest pain symptoms at 1 year.9 For patients with normal angiography, although coronary disease may be absent, the impact on their perception of health and quality of life is relevant. The diagnostic result of the angiogram itself may confer an immediate impact on health status. Initially, this may be a positive effect10 but the sense of ‘relief’ certainly does not persist over time with decreased health status including lower quality of life and perceived control observed in NoCAD patients compared with CAD.11 Health status outcomes in coronary artery disease. Health status outcomes reflect the ways in which the underlying disease manifests itself to patients—symptoms, function, and quality life. Adapted from Spertus et al.6 Health status outcomes in coronary artery disease. Health status outcomes reflect the ways in which the underlying disease manifests itself to patients—symptoms, function, and quality life. Adapted from Spertus et al.6 The results of the study by Hanssen et al.,12 extend our understanding of health status for patients with NoCAD. In this study, 459 consecutive patients without known CAD undergoing elective coronary angiography were prospectively assessed for 1 year using self-report assessments of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). The sample were relatively young (mean age 62 years) and 57% were male. Obstructive CAD was evident in 38% of patients and of the 62% with normal angiograms, 41% showed smooth arteries (<20% stenosis). The baseline HADS demonstrated moderate to severe anxiety symptoms in approximately one in four patients and moderate to severe depression symptoms in one in five patients. No differences in scores were observed by angiogram findings at baseline. At 6 months post angiography, cross sectional analysis revealed lower scores, indicating better health status, in patients with obstructive CAD. This included a lower proportion of patients with moderate to severe anxiety symptoms, identified by a HADS-A score greater than eight. Longitudinal analysis demonstrated a significant improvement in both the HADS-A and HADS-D scores across all patients. These changed over time, with the worst scores occurring soon after index angiography and the greatest improvement in scores evident in the first 6 months. Of importance, the largest improvement in scores was observed in patients with obstructive CAD and the smallest improvement in those with smooth vessels. Moreover, NoCAD was an independent predictor of increased HADS-A scores at 12 months, in addition to baseline anxiety and levels of physical activity. Patients with NoCAD have impaired health status when compared with a general population,13 including a poorer quality of life and increased psychological distress. In the study, by Hanssen et al.,12 patients with obstructive CAD demonstrated significantly lower levels of anxiety and depression over time in comparison to patients with NoCAD, despite baseline health status being similar. The reasons for this difference over time are likely to be complex and require further evaluation of additional health domains, including the prescribed treatments and symptomatic status. The authors do not present data on subsequent revascularization or cardiac medications but it is likely that patients with obstructive CAD underwent further therapies providing relief from cardiac symptoms and possibly reassurance that their disease had been adequately managed, relieving their mental health burden. Further, the chest pain status of patients in the study is unknown. This is an important limitation as symptomatic status is a key determinant of a patient’s perception of their health. In patients with CAD, frequent chest pain symptoms as measured by the Seattle Angina Questionnaire are associated with worse quality of life.14 For patients with NoCAD, functional outcomes should not be dismissed as many remain symptomatic with over 50% of patients continuing to report ongoing chest pain causing limitations in daily life activities, and some suffering from persistent chest pain for many years. Seattle Angina Questionnaire scores over 12-months following angiography also show a significantly delayed improvement for patients with NoCAD when compared with CAD patients.13 This is particularly relevant as some patients with NoCAD have an ischaemic basis for their chest pain via mechanisms such as abnormal coronary vascular resistance or endothelial dysfunction. These patients may benefit from further invasive evaluation such as coronary haemodynamic studies to identify the source of the coronary vasomotor dysfunction (involving the large epicardial vessels or microvasculature) and thereby, providing direction for future therapy options. The differences in health status observed in the current study also reflect the role of psychopathological disorders as an important differential diagnosis in patients with angiographic exclusion of CAD. Association with anxiety states, such as panic disorder and somatoform disorders15 have been reported. Unfortunately, these disorders are often not recognised and may heavily burden the healthcare system. An angiogram that does reveal cardiac disease may also perpetuate the patient’s anxiety as there is no explanation for symptoms or pathway for intervention, as indeed suggested by Hanssen’s findings. As studies have uncovered concern in relation to prognosis in NoCAD patients, attention also needs to focus on assessing and improving well-being in these patients. This cannot be emphasised enough. Although scores on health status assessments are perceived to be ‘soft’ endpoints, they are in fact independently predictive of prognostic outcomes, and therefore, can be considered as providing additional risk stratification information.16 In addition to quality of life limitation, NoCAD patients are prone to ongoing healthcare utilization with subsequent evaluation and management highly variable among clinicians. Although efforts to develop management pathways are in progress,17 improving our present clinical practice may be achievable now by implementing care that is guided by patients’ reports of their health status. Measuring symptom burden, functional capacity, and physical and mental quality of life allows for informed clinical decisions. The health status trajectories should be considered as part of any evaluation of prescribed therapies. For example, if improvements in chest pain symptoms over time do not correlate with improvements in quality of life, then examination for psychological conditions may be considered. Health status assessments enhance the clinician’s understanding of the patient’s disease burden, and also provide opportunities for the patient to be involved in their care, thereby promoting engagement in shared-decision making. In this way, care is patient-centred and on a pathway towards being individualized. Truly personalised medicine requires quantification and understanding of an individual’s risks, benefits and expected outcomes of treatment, and necessitates new health tools that can assist in this decision-making process. Currently, even, the use of health status assessments has not yet evolved as an integrated clinical tool to compliment contemporary practice. Much work is needed to bridge this gap. The finding of normal angiography may be viewed as a paradox, in that the knowledge of no coronary disease on one hand provides comfort, but for the patient it can also be what causes the most anxiety. For clinicians, it presents a very real challenge but at the same time, an important opportunity to drive efforts in establishing a foundation for further evaluation of these patients where quantifying, interpreting, and managing health status is at the core. Conflict of interest: none declared.