Impact of cardiac condition on wound healing and recurrence in patients with chronic limb-threatening ischemia undergoing revascularization

Background Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral artery disease. Although cardiac conditions adversely affect the prognosis of CLTI patients, it remains unclear which specific cardiac parameters impact wound healing and recurrence after revascularization. Purpose This study aimed to investigate which cardiac conditions are associated with wound healing and wound recurrence in CLTI patients with tissue loss who underwent revascularization. Methods This multicenter, retrospective study enrolled 1831 CLTI patients (median age 76 years, male: 61.3%, diabetes: 65.0%, hemodialysis: 50.4%, median ejection fraction: 64% [55, 69], heart failure [HF]: 13.2%, coronary artery disease: 51.2%, atrial fibrillation [AF]: 15.8%) with tissue loss (median ankle brachial index: 0.64 [0.51, 0.79], WIfI [Wound, Ischemia, and foot Infection] clinical stage 4: 44.1%) who underwent endovascular therapy between April 2010 and March 2024. Outcomes were wound healing and wound recurrence. Kaplan-Meier analysis was used to assess rates, and Cox proportional hazards regression analysis was used to identify associated factors. Results During a median follow-up of 15 months, wound healing occurred in 978 patients and recurrence in 291 patients. The Kaplan-Meier 1-year rates for wound healing and recurrence were 57.8% and 17.6%, respectively. In univariate analysis for impact of cardiac parameter on wound healing, history of HF was the strongest cardiac factor associated with wound healing. In multivariate analysis, age ≥ 75 years (hazard ratio [HR] 95% confidence interval [CI]: 1.21 [1.06-1.39], p=0.006), body mass index < 18.5 kg/m2 (HR: 0.76 [0.64-0.91], p=0.003), non-ambulatory status (HR: 0.73 [0.63-0.84], p<0.001), hemodialysis (HR: 0.79 [0.69-0.90], p<0.001), Serum albumin < 3 g/dL (HR: 0.72 [0.62-0.85], p<0.001), WIfI clinical stage, per 1-stage increase (HR: 0.91 [0.85-0.98], p=0.008) were significantly associated with wound healing but the history of HF was not (HR: 0.81 [0.64-1.01]. p=0.058). Interaction analysis revealed a more marked decreased risk of wound healing in the HF group in patients without AF (p for interaction=0.015). The 1-year wound recurrence rate was significantly higher in patients with HF than in those without (24.2% versus 17.0%, log-rank p=0.003). Multivariate analysis revealed that hemodialysis (1.96 [1.51-2.55], p<0.001) and history of HF (1.63 [1.10-2.42], p=0.015) were significantly associated with wound recurrence. Conclusion This study showed that a history of HF is a strong and significant factor associated with wound recurrence after revascularization in CLTI patients. Although a history of HF was not an associated factor with wound healing, its negative impact was significantly modified by the absence of AF. These findings suggest that HF status, particularly its interplay with AF, should be considered in the long-term wound management of CLTI patients.