Association between QTc interval prolongation and outcomes of diabetic foot ulcers: Data from a 4-year follow-up study in China
Introduction
Diabetic foot ulcers (DFU), are frequent and disastrous complication of diabetes [1], [2], [3], often leading to lower extremity amputation (LEA). A large number of references reported that DFU was associated with an increased risk of cardiovascular events [4], cardiovascular deaths [5], [6] and all-cause mortality [6], [7], [8]. Some Refs. [1], [9], [10] and part of our previous studies [11], [12], [13] also reported that DFU population was in bad conditions and having poor prognosis. A number of risk factors contribute to the development [14], [15], [16], [17] and prognosis [17], [18], [19], [20], [21], [22] of DFUs, including previous amputation, previous foot ulcer history, peripheral neuropathy or foot deformity, peripheral artery disease (PAD), impaired vision, smoking, and renal impairment. Recent research [15], [23] revealed that cardiac autonomic neuropathy (CAN) was also independently associated with the development of DFUs in patients with type 2 diabetes. However, the association between CAN and DFU prognosis still remains unclear.
CAN [24], a common complication of diabetes, often diagnosed by Ewing methods (measuring heart rate variability during a Valsalva maneuver, deep breathing, and upright posture), was significantly related with cardiovascular disease (CVD) and CVD-related mortality [25]. One research reported that CAN also was a simple, noninvasive marker of an imbalance or disturbance between sympathetic and parasympathetic (vagal) activity in the lower extremities [26]. The disturbance may cause sympathetic denervation of the skin, with reduced nutritive capillary blood flow and impaired wound healing. It was indicated that QTc interval prolongation was a reasonable predictor for CAN in diabetic patients [27]. QTc interval prolongation was also reported [27], [28], [29] to be associated with autonomic failure in patients with diabetes, could further predispose these patients to sudden arrhythmia and death. Thus, whether the simple term QTc interval prolongation can be used to independently predict DFU patients’ death or ulcer related outcomes really interested us.
In this observational prospective study, we assessed whether QTc interval prolongation was associated with wound healing, ulcer recurrence, all-cause or specific death, and nonfatal cerebral and cardiovascular events (NCCE) in DFU populations. To our best knowledge, this was the first long term prospective study of such scale to investigate these associations.
Section snippets
Subjects
From March 2009 to December 2012, a total of 732 patients hospitalized in our department for DFU were consecutively recruited. However, only patients who had all inclusion criteria and none of exclusion criteria were included. Briefly, the inclusion criteria were: (1) aged ≥18 years old when admitted; (2) the diagnosis of diabetes were confirmed or were in anti-diabetic medication or insulin therapy; (3) with at least one ulcer located at or below the ankle. The exclusion criteria were: (1) not
Results
By the end of this study, the median follow-up time was 48 months, ranging from 0.2 to 86 months.
Discussion
In this cohort study, we analyzed the association between QTc interval and ulcer related or patients related outcomes in DFU population. We found that QTc interval prolongation was an independent predictor of cardiac sourced mortality in DFU patients. Although supported by abundant previous theoretical foundation and univariate analysis in this study, the independent association of QTc interval prolongation with all-cause death, ulcer’s healing, recurrence, cerebral cardiovascular death, as
Conclusion
QTc interval was an independent risk factor for cardiac death, but not for all-cause deaths or NCCVE in DFU patients. It neither independently associated with diabetic foot ulcers’ healing nor recurrence.
Acknowledgement
Funding from the Chinese Scientific Research Project of Medical Public Welfare Industry Foundation (201502007) was gratefully acknowledged. No potential conflicts of interest relevant to this article were reported. Zhengyi Tang designed this study, reviewed the data and manuscript, and was the guarantor of the work. Shumin Wang collected and analyzed the data and drafted manuscript. Yang He, Lei Xu, Shanshan Zhang make many contributions to data collection. Junyi Gu, Jianyuan Shi, Yaping Shen
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