Radionecrosis Induced by Cardiac Imaging Procedures: A Case Study of a 66-Year-Old Diabetic Male with Several Comorbidities

Author Affiliations: From the Center for Wound Care & Hyperbaric Medicine at Grenada Lake Medical Center, Grenada, Mississippi. The author reports no conflicts of interest regarding the content herein. Manuscript submitted December 7, 2007, provisional acceptance given March 10, 2008, and accepted March 20, 2008. Address for correspondence: Liza De Olazo Banaag, MD, Center for Wound Care & Hyperbaric Medicine at Grenada Lake Medical Center, 965 J. K. Avent Dr, Suite 100-A, Grenada, MS 38901. E-mail: liza.banaag@glmc.net

_______________________________________________ ABSTRACT: Radionecrosis is a rare sequitur of cardiac catheterization and imaging procedures. A 66-year-old diabetic male with several comorbidities developed a scapular burn immediately after the last of 3 cardiac catheterization and stenting procedures conducted over a 3-year period. The burn subsequently developed into a large eschar that required extensive debridement, a prolonged treatment of hyperbaric oxygen therapy, and plastic surgery to heal. Wound healing was compromised by the patient’s diabetes and a potentially long course of steroids prescribed for other medical problems. Primary clinicians should be aware of suspicious-looking wounds that develop subsequent to cardiac catheterizations, especially in diabetic patients.

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J INVASIVE CARDIOL 2008;20:E233–E236 Radiation necrosis has been defined as the exposure of tissue to any kind of radiation and profile that results in hypoxia, hypocellularity, and hypovascularity of the tissue bed.1 The vast majority of cases arise from radiation therapy for cancer treatment in which adjacent healthy tissues are damaged,2 the effects of which are categorized as acute, consequential, or late.3 Late effects, meaning appearance months or years after the insult, can be particularly devastating, and can happen with a surprisingly high frequency. For example, osteoradionecrosis, which has been characterized as exposed irradiated bone that fails to heal over 3 months,4 has been reported at a rate of 8­–15%.5,6 The effects of late radionecrosis are also poorly understood, but according to Stone et al, involve damage to the vasculature and release of vasoactive cytokines, thus leading to collagen deposition, the formation of thrombi, and death to slow-growing parenchymal cells.2 In contrast to cancer treatment, radiation necrosis resulting from prolonged exposure to ionizing radiation during cardiac interventional procedures that involve fluoroscopy, cineradiography, and intravascular brachytherapy appears to be a relatively rare event, although the true incidence is not known.7–14 Most of these cases initially described the injury as a skin lesion or skin eruption with telangiectasia, or an ulcerative lesion, sometimes identified initially as contact dermatitis12 or a drug eruption.11 Frequently, such cases are misdiagnosed. For example, 1 patient who developed a painful and erythrematous area of skin that ulcerated and then necrosed over a 5-month period testified in court during a malpractice case that he visited 5 physicians before receiving a correct diagnosis.14 If one looks for patterns within the cases, 2 observations stand out: 1) the right scapular region or upper back area is a common location; and 2) these patients had undergone either extensive coronary angioplasty or angiographic procedures that were complicated and long in duration, or there were multiple procedures due to subsequent complications or developments over a relatively short period of time (a few weeks to 1 or 2 years), thus increasing the radiation dose received in a relatively small area of tissue. The fact that prolonged or repeated cardiac angiographic procedures can place patients at much higher risk for developing radionecrosis of skin tissue has apparently not been sufficiently stressed among many cardiologists,14 though such warnings to radiologists were published as early as 1991. These warnings stressed that high-level fluoroscopic equipment could cause patients to absorb dose rates of 0.93 Gy (93 rads) per minute.15 Shortly thereafter, the FDA issued a series of public health advisories regarding the use of fluoroscopy, culminating in an advisory specifying which patients should have radiation exposure recorded, and how this should be accomplished.16 Several standards published by the American College of Radiology have also addressed this issue.14 In the diabetic population, both angiographic restenosis and the need for repeat revascularization are more common compared to nondiabetic patients.17 In addition, it is suspected that individuals with diabetes and/or connective tissue diseases might be more sensitive to radiation, thus lowering the threshold dose at which a skin response might occur.12 Therefore, it is possible that this group might be at even higher risk for radiation-induced dermatitis. Radionecrosis can present in many different ways, and its course will depend on recognition, treatment, and comorbid factors.7 For example, it is possible that a mild burn might not be correctly diagnosed because it is not linked to a previous procedure. This was initially the case in a 66-year-old white male with a complex medical history who initially presented for shortness of breath, fever, and increasing weakness, but also had a burn on his right shoulder. Case Report. The patient described here gave his consent for this case study to be considered for publication. The treatment of this patient conformed to our institutional guidelines, and those of the American Physiology Society. The patient had both long-standing coronary arterial disease (CAD) and type II diabetes mellitus with peripheral neuropathy. In addition, he had a history of chronic renal disease, hypertension, morbid obesity, hyperlipidemia, gastroesophageal reflux, gout, and more recently, peripheral vascular disease. Both parents died of lung cancer, and his brother also has a significant history of CAD. The patient smoked 3 packs a day of cigarettes for more than 20 years, but quit 30 years ago, and was not a user of alcohol or drugs. Despite his cormorbidities, the patient was in relatively good health until he presented with an inferior-wall myocardial infarction and complete heart block on February 10, 2003. As a result, he underwent left heart catheterization, right coronary artery (RCA) AngioJet® (Possis Medical, Minneapolis, Minnesota) rheolytic thrombectomy, angioplasty, and stent implantation. Following a laparoscopic cholecystectomy in December of 2004, he complained of angina pectoris in March of 2005, and underwent angioplasty and stenting of the proximal RCA (Figure 1). Six months later, his anginal symptoms reappeared, requiring repeat angioplasty to the same artery and 2 more stents that were placed in the distal and proximal segments. The last 2 procedures were extremely difficult to perform and it was noted that high cumulative radiation dosages were employed during the imaging procedures, although drug-eluting stents were utilized, so no concurrent radiation was given to prevent restenosis. A few weeks after the last cardiac procedure, the patient noticed a large square-shaped burn on his right shoulder, but did not connect it with the procedure, and it was not treated. In January 2006, the patient visited the emergency room, complaining of shortness of breath. He was diagnosed with a large pleural effusion and subxiphoid pericardial drainage was performed. The effusion was bloody, but cytology and pathology were negative for malignancy. Two months later, a second effusion occurred, and a left thoracoscopic window was created. In early April 2006, a third effusion was apparent after the patient complained again of shortness of breath, and this was relieved with a pleural tap. The recurring effusion was believed to be the result of the pericardium window, though infection, an autoimmune inflammatory process or pericarditis were not ruled out at this stage. Since the fluid was draining into his chest and not being reabsorbed, the options were a repeat thoracentesis, implantation of an in-dwelling catheter, or a course of steroid treatment. In addition, it had become apparent that the patient had developed anemia, vitamin B12 deficiency, and bilateral leg edema, which was partially treated with ankle bandaging. After numerous consultations and eliminating gastrointestinal blood loss as a cause of the anemia, it was decided to start the patient on oral steroids (prednisone, 20 mg). In early May 2006, the patient complained of dizziness, confusion, falling at home, feeling very weak, and having chills and fever. His temperature was 102.8º F, his pulse was 112, his respiratory rate was 22, and his blood pressure was 154/75. His lungs were clear by auscultation, with a negative chest X-ray, and there were no cardiac abnormalities. However, a necrotic ulcer was observed on the right heel, with significant erythema extending up the leg to the knee. Evidence of cellulitis in the right leg secondary to an infected foot ulcer was buttressed by a white blood cell count of 21,000. In addition, his diabetic condition, which was normally controlled by Humulin NPH (35 units daily) and Humulin-R (Eli Lilly and Company, Indianapolis, Indiana), as needed, appeared to be temporarily out of control, with a blood glucose of 372 mg/dL, although his HbA1c of 8.1 indicated good management overall. The patient was treated with intravenous piperacillin and tazobactam (Zosyn, Wyeth Pharmaceuticals, Inc., Philadelphia, Pennsylvania) and his Humulin NPH was increased to 45 units daily. The diabetic foot ulcer was drained, underwent 3 debridements, and finally healed by late October with the use of vacuum-assisted closure negative-pressure wound therapy. The patient’s shoulder wound had also deepened and become very painful, measuring approximately 6 cm x 3.3 cm, with a 1 cm erythema extending outside of the wound boundary, as well as dilated capillaries (Figure 2). After initial debridement, a biopsy was performed since the tissue felt very tough, as though it were plastic. The pathologist reviewing the biopsy indicated it was suggestive of radionecrosis, although the history and findings of the wound did not seem to be consistent with the diagnosis. Since the patient could not tolerate conventional wound care dressings, and because radionecrosis was suspected, a course of 30 hyperbaric oxygen (HBO) treatments (Marx protocol18) were given, followed by debridement and closure with plastic surgery and 10 more HBO treatments. The wound responded to HBO therapy (Figure 3), and by the end of 2006, had healed completely. Discussion. Given the location of the wound and its appearance immediately after the last coronary intervention, there seems little doubt that the wound was radiation-induced. Both of the last 2 procedures involved extensive imaging of the coronary vasculature, as well as angiograms of the right femoral and iliac arteries in the last procedure to exclude a possible pseudoaneurysm versus an arteriovenous fistula. A similar case was recently reported in a diabetic patient who underwent multiple fluoroscopy-guided cardiac procedures.19 However, in the case reported here, the development of the wound was certainly influenced by the diabetic condition of the patient, as diabetes is well known for increasing the risk of wound initiation and infection, as well as impeding healing.20,21 Although steroid administration generally depresses wound healing,22 it is unclear whether the prolonged steroid course prescribed for the patient exacerbated the scapular wound, since we did not know the state of the patient’s hypothalamus-pituitary axis at the time. HBO therapy, which requires uninterrupted daily treatments for optimum efficacy, was delayed in part due to the patient’s multiple medical problems, otherwise it would have been initiated sooner. The estimated threshold radiation dosage to induce radionecrosis is estimated to be between 6 and 25 Gy,12,23–25 whether it is a single exposure or a cumulative exposure over a period of several years. For diabetic individuals, it is not known what the threshold for injury is versus healthy individuals, but it must be assumed that the threshold dosage is lower, especially when the diabetes is uncontrolled. Moreover, while a radiation-induced lesion typically appears within 0–3 months after radiation exposure, it can manifest itself years later. Consequently, cardiovascular specialists should be advised to estimate dosages during an intervention and include them in medical records so that primary care physicians can be alerted if the estimated dosage exceeds 6 Gy. Diabetic patients should also be informed regarding the risks of developing radiodermatitis during vascular imaging procedures so that any suspicious dermatitis can be promptly treated. In this case, it was not until the biopsy findings were known that we associated the wound with the previous cardiac procedures. As cardiac and other vascular interventions become more sophisticated and effective and are increasingly employed in a population that has a high prevalence of diabetes, it is likely that that the incidence of such events will increase unless measures are taken to decrease absorbed dosages. It might be assumed that improvements in imaging technology will mitigate this problem, but a number of concerns exist. First, there is a substantial variation (4- to 6-fold) in fluoroscopic exposure rates due to habitus conditions, the type of X-ray system, vendor, and geographic region, with no association with improved image quality.26 As Laskey et al state, “cardiac catheterization laboratories must minimize such potentially harmful variability in X-ray exposure.”26 Second, filmless (digital) acquisition does not appear to reduce exposure.27 Third, it has been assumed that pulsed fluoroscopy clearly reduces patient exposure to radiation,28–31 but recent evidence suggests that this is not the case unless the pulse rate is reduced to less than 25 pulses/second.32 Finally, the dose-area product, or DAP, which has been accepted as the conventional method for estimating radiation exposure,33 may be inadequate for determining maximum skin dosage. In conclusion, although prevention of radionecrosis is important, perhaps the most important message that can be conveyed is to increase awareness that radionecrosis is a possible outcome in those patients at increased risk. Communication of this risk to all physicians treating the patient, as well as the patient him/herself, will help minimize possible misdiagnosis and accelerate early treatment. Acknowledgments. The author would like to thank all the physicians and nurses who cared for this patient and documented their findings in their case notes.

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