Immunosuppression Medication and Cardiac Function Improvement Treatments Might Prevent Takayasu Arteritis Patients with Aortitis from Receiving Cardiac Surgery
Takayasu arteritis (TA) is a non-specific large-vessel vasculitis characterized by granulomatous inflammation of the vascular walls. It is a significant cause of aortitis, accounting for 53% of cases. Aortitis in TA patients often involves the aorta, aortic root (including the ring and sinus), and valves, leading to severe complications such as aortic stenosis, dilation, aneurysm, dissection, aortic valve insufficiency, and perivalvular leakage. These complications can result in heart failure and increased mortality. While medication treatments, including glucocorticoids, traditional immunosuppressive agents, and biological agents, are the cornerstone of management for TA patients with aortitis, some patients may also benefit from cardiac surgical interventions such as aortic valve replacement (AVR), Bentall procedure, coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI). However, the prognosis of TA patients with aortitis remains unclear, and this study aimed to investigate their clinical outcomes and explore associated factors to guide healthcare practices.
The study enrolled 115 patients with TA and aortitis from a prospective TA registry study in East China, which began in 2009. The participants met the 1990 American College of Rheumatology classification criteria for TA and were evaluated at baseline for demographics, manifestations, comorbidities, laboratory and radiological examinations, and disease activity. Patients were included if they had imaging findings (such as computed tomography angiography, magnetic resonance angiography, positron emission tomography, or echocardiography), intra-operative visible findings (such as congestion, edema, thickening, pseudoaneurysm, prolapse, tear, or perivalvular leakage), or pathological findings (non-infectious inflammation in vascular and valvular tissues). Patients with atherosclerosis, infection, tumor, rheumatic diseases, systemic vasculitis, or congenital heart diseases were excluded.
The primary outcome of the study was the acceptance of primary cardiac surgeries by TA patients with aortitis, while the secondary outcome was the occurrence of secondary cardiac surgeries (reoperations). Disease activity was evaluated using the Kerr score, and cardiac function was assessed using the New York Heart Association (NYHA) classification. Univariate analyses compared disease activity, cardiac function, medications, and examinations between patients with and without the study outcomes. Multiple logistic regression analyses were conducted to determine independently associated factors with the study outcomes, expressed as odds ratios (OR). Kaplan-Meier curves were used to show the time to outcomes. Clinical remission was defined as having no new-onset or aggravated manifestations, with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) decreasing to normal levels, and a glucocorticoid dose of ≤15 mg/day.
The study found that 87.8% of the patients were evaluated as active at baseline, with 71.3% receiving immunosuppression medications. These medications included monotherapy with glucocorticoids (mean dose: 31.4 ± 16.0 mg/day) and combined regimens of glucocorticoids with other immunosuppressive drugs such as hydroxychloroquine, cyclophosphamide, leflunomide, mycophenolate mofetil, thalidomide, azathioprine, and methotrexate. Cardiac function was evaluated using the NYHA classification, with 37 patients classified as NYHA class I, 20 as class II, 53 as class III, and 5 as class IV.
During a mean follow-up period of 39.1 ± 30.2 months, 57.4% of the patients achieved both clinical remission and improved cardiac function to NYHA class I-II after receiving immunosuppression medications. Among these, 43 patients were originally active with NYHA class I-II, and 23 were active with NYHA class III-IV. Other active patients with NYHA class III-IV included 16 who achieved remission but did not improve in cardiac function and eventually underwent cardiac surgeries, and 19 who received cardiac surgeries directly without prior immunosuppression treatments. At the end of the follow-up, 35 patients had undergone primary cardiac surgeries, including ten Bentall procedures, eight AVR, five aorta replacements, six CABG, two PCI, and one other bypass graft. Among these, five patients underwent secondary cardiac surgeries, including two PCI for restenosis, two AVR for perivalvular leakage, and one aortic valve repair for valve perforation. One patient died from liver and kidney insufficiency within 30 days after surgery. Sixteen patients continued post-operative immunosuppression medications, and 30 achieved clinical remission and improved cardiac function six months post-operatively. Significant improvements were observed in platelet levels, fibrinogen, ESR, CRP, internal diameter of the aortic root, left ventricular end-systolic diameter, posterior wall thickness of the left ventricle, and ascending aorta width.
Patients who underwent at least one cardiac surgery were more likely to have NYHA class III-IV (100.0% vs. 28.8%), a higher internal diameter of the left atrium (45.5 ± 6.4 mm vs. 37.8 ± 3.9 mm), and a lower rate of receiving medication treatments (37.1% vs. 93.8%) compared to those who did not undergo surgery. Multiple logistic regression analysis identified NYHA class III-IV as a risk factor for primary cardiac surgery (OR = 6.7, 95% CI: 2.6–17.1), while immunosuppression medication treatments were protective (OR = 0.3, 95% CI: 0.1–0.5). Kaplan-Meier curves showed that patients with NYHA class III-IV were more likely to undergo primary cardiac surgery than those with class I-II. Patients without immunosuppression medications all underwent primary surgeries within the first 12 months, significantly different from those with medications. All patients who underwent secondary cardiac surgeries were in NYHA class III-IV, and there was no significant difference in secondary surgery rates between patients with and without pre-operative immunosuppression medications.
The study concluded that 60.3% of active patients with NYHA class III-IV underwent cardiac surgeries during follow-up, with a risk of primary cardiac surgeries within the first 15 months and secondary surgeries six months after the primary ones. Immunosuppression medications were shown to control disease activity, stabilize or improve cardiac function, and prevent or postpone primary cardiac surgeries, particularly for active patients with NYHA class III-IV. The mean time from medication to remission was 4.7 ± 1.9 months, and from medication to surgery was 11 months. Pre-operative immunosuppression treatments significantly improved post-operative outcomes, particularly by reducing the incidence of secondary surgeries. Therefore, early and sufficient immunosuppression medication treatments may benefit TA patients with aortitis by achieving dual remissions in both disease activity and cardiac function, leading to better outcomes.
doi.org/10.1097/CM9.0000000000001160
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