Frequency of subclavian artery stenosis in patients with mammarian artery coronary bypass and suspected coronary artery disease progression

In the current study, we retrospectively analyzed a large, multicenter patient cohort with IMA coronary bypass presenting for coronary angiography and suspected CAD progression over a period of more than 20 years for the presence of subclavian stenosis. With data from almost 4000 individuals, this study presents the largest population addressing this question to this date.

Prevalence of subclavian stenosis

Subclavian stenoses ipsilateral to the IMA grafts were present in about 2% of patients, two-thirds of which were classified as severe. The prevalence of subclavian stenosis in the general population is reported at about 2–4% and may be as high as 7–18% in patients with PAD [8, 16, 17]. In several studies screening for subclavian stenoses in patients with CAD referred for potential CABG surgery, the prevalence was 2.5–6.8% [8, 10, 12, 13] with 2.5% in the largest population (1,498 patients) [12].

There are different explanations for the slightly lower frequency in our study: first, our population differs significantly when compared to the published pre-CABG populations in several regards. On the one hand, patients with significant subclavian stenosis may have been treated or excluded from IMA-bypass grafting prior to surgery in our study. State-of-the-art pre-CABG diagnostics provided, most of the subclavian stenoses identified in our study should be de novo stenoses occuring after bypass surgery. However, the subclavian stenoses in our study may in part reflect the prevalence of lesions that were not detected before CABG surgery and in part the new incidence of stenoses that developed after CABG surgery.

On the other hand, average patient age in our population was 80 years and therefore older than published pre-CABG populations, which may positively or negatively affect prevalence and incidence of subclavian stenoses. While an older population would generally be considerd to have an increased burden of polyvascular disease, the condition studied may also have a negative prognostic impact over time.

Secondly, our study was purely retrospective and no prospective screening procedure was performed. Thus, it is possible that subclavian stenoses were missed during the clinical workup of patients. Particularly mild and moderate stenoses may not have been identified by non-invasive blood pressure measurement, invasive blood pressure measurement during coronary angiography, and particulary when performing only selective IMA angiography.

Interestingly, we saw an increase in the number of patients diagnosed with subclavian stenosis over time (Supplemental Fig. 3). This documented rise is most likely caused by an increased awareness of this relevant medical condition in everyday clinical practice, improved screening algorithms including the implementation of routine bilateral blood pressure measurement in all patients, and improved availability of high quality duplex ultrasound. Considering this change in diagnostic prevalence over time, we cannot rule out that significant stenoses may have been missed. In patients with subclavian stenoses, female gender was more frequent compared to the overall population (35% vs. 18%). The reasons for this difference may be related to vessel size, sex differences in vascular biology, or to chance in our population. Further analyses are required for a improved understanding of sex differences in the presentation and pathophysiology of vascular disease.

Treatment strategies

Endovascular treatment is feasible for many patients with subclavian stenosis, and endovascular and surgical treatments generally achieve good results at low complication rates [5, 12, 18]. In the current study, only half of the patients with severe subclavian stenosis received endovascular or operative revascularization of the subclavian artery. Within the other half, two-thirds underwent PCI either in the native coronary vessel receiving the bypass, thereby compensating for the insufficient IMA graft function, or PCI in a different coronary vessel considered the target lesion at the time of diagnosis. The remaining third (11% of patients with ipsilateral subclavian artery stenosis) did not receive any revascularization procedure. Documented reasons for a complete conservative treatment decision included negative ischemia testing, insufficient or occluded IMA graft, limited putative benefit, and failure to present for scheduled ischemia testing or revascularization. In some cases, no reason was documented. Considering age and morbidity of the patient population, conservative treatment numbers appear acceptable. Nevertheless, the presence of occluded IMA grafts in 9% of patients with subclavian stenosis raises the question, if some of these IMA graft occlusions occurred as a consequence of the subclavian stenosis and could have been prevented by earlier diagnosis and treatment. 73% of patients with severe stenosis who received subclavian revascularisation reported symptom relief. This rate was numerically lower in the other groups, suggesting benefit from subclavian revascularistation, although numbers were too low to draw valid conclusions.

Clinical significance and screening

Subclavian artery stenosis in patients with IMA grafts may present in various clinical forms, as sudden death, myocardial infarction, stable angina, or progressive LV dysfunction [3, 4]. Therefore, subclavian stenosis should always be considered in patients with IMA graft and cardiac symptoms. We believe that subclavian stenosis in patients with ipsilateral coronary artery IMA-bypass graft should never be considered a benign condition and requires systematic diagnostic testing and treatment in many cases. Depending on the supply area of the IMA graft, its prognostic significance may be comparable to a significant stenosis of the left main coronary artery in individuals without CABG.

Even so, due to the frequent lack of symptoms and the benign course of the condition in asymptomatic patients without coronary IMA graft, there is still limited awareness and likely a significant underdiagnosis of the condition, despite the simplicity of its diagnosis.

Diagnosis of subclavian stenosis is easily established by non-invasive testing. Bilateral blood pressure measurement and additional color duplex ultrasonography in case of ≥ 15 mmHg inter-arm blood pressure difference are simple and cost-effective screening tools with acceptable sensitivity for the identification of severe subclavian stenoses [19].

Finally, in patients with an IMA graft and known subclavian stenosis, guidelines recommend ischemia testing [6]. Yet, in our experience, treadmill exercise or pharmacologic testing may not detect clinically relevant subclavian steal phenomena induced by brachial exercise. Hand grip exercise testing can be used to detect clinically relevant ischemia [2, 20]. Development of standardized testing procedures for all patients with IMA grafts undergoing ischemia testing need to be established.

Limitations

The current multicenter study has all important limitations related to its retrospective design. Subclavian stenoses were graduated semiquantitatively by the treating clinicians at the time of diagnosis based on several parameters. A large number of patients received more than one coronary angiography. The high average age and the population may not ideally represent other populations. Most importantly, lacking a prospective screening approach, we cannot rule out that subclavian stenoses were missed during the clinical workup of patients.

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