Rhabdomyolysis in an HIV-infected patient following coronary angiography: case report and literature review

Introduction

Ischaemic heart disease is being observed with increasing frequency among human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy (cART).^1,2 These patients may undergo coronary computed tomography angiography, invasive coronary angiography and percutaneous coronary interventions, all of which entail the administration of radiographic contrast media.

In the present report, we describe, to the best of our knowledge, the first case of an HIV-infected patient treated with cART in whom coronary angiography was complicated by rhabdomyolysis. We also discuss the relationship between rhabdomyolysis, iodinated contrast media and cART.

Case report

A 52-year-old Caucasian man with HIV was admitted to the cardiology ward of our Institute for exertional angina. The patient had been on cART since 1996. More precisely, since 2007 he was taking the protease inhibitors (PIs) saquinavir (500 mg in the morning and 1000 mg in the evening) and ritonavir (100 mg OD), as well as the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (150 mg BD) and zidovudine (300 mg BD). Plasma viraemia was stably suppressed (<50 copies/mL) and immune recovery was satisfactory (CD4⁺ T cell count of 550/mm³). A concomitant use of other pharmaceutical products or recreational drugs was denied by the patient, who did not present any other concomitant disease.

An exercise electrocardiogram was positive for ischaemia at a moderate work load (100 Watt). Thus, coronary angiography was performed with 110 mL of isosmolar iodinated X-ray contrast medium (Iomeprol 350 mg/mL) and showed left main and three-vessel diseases.

The following day, the patient developed aesthenia and muscular pain. Laboratory tests showed an increase in creatine kinase (CK) and myoglobin levels up to 7611 UI/L and 2089 ng/mL, respectively. Interestingly, myoglobin was within the normal range at baseline, while CK levels were slightly increased (228 UI/L).

Suspecting rhabdomyolysis, the patient was hydrated (2 L normal saline solution per day), maintaining a daily diuresis greater than 2 L and preserving renal function. Creatinine was 0.89 mg/dL at baseline (creatinine clearance 88 mL/min/1.73 mq) and 0.78 mg/dL two days after contrast administration. Five days after coronary angiography, symptoms completely disappeared and laboratory tests returned to normal values.

The patient underwent electromyography which revealed a myogenic pattern. Ischaemic forearm exercise test was also performed which showed a slight increase in the production, with delay in normalisation, of lactic acid, associated with a normal ammonia value. Muscle biopsy was not performed in view of the severity of coronary artery disease that required urgent surgical revascularisation. The patient was, therefore, treated with on-pump quadruple coronary artery bypass grafting and post-operative course was uneventful.

Discussion

We describe a case of temporal association between rhabdomyolysis and administration of hypo-osmolar iodinated X-ray contrast medium suggesting a causal relationship.

Two cases of rhabdomyolysis following contrast medium administration have been described in non-HIV patients,^3,4 and in both cases renal disease coexisted.

Our patient after coronary angiography maintained a normal renal function, but the increased baseline CK levels could have been indicative of underlying muscular damage. This damage conceivably may have been secondary to mitochondrial dysfunction caused by NRTIs. ⁵ In fact, our patient had an ischaemic forearm exercise test compatible with mitochondrial dysfunction. ⁶ The notable increase in skeletal muscle enzymes could have been, therefore, secondary to lactic acidosis triggered by the iomeprol administration in the context of a pre-existing suffering muscle, as previously described with co-administered iodinated X-ray contrast media and biguanides. ⁷ Coincidentally, lactic acidosis has been linked to therapy with NRTIs as well. ⁸

It should be pointed out that the antiretroviral therapy taken by our patient was not in accordance with current guidelines. ⁹ Our patient was treated in a non-standard fashion due to the fact that he did not undergo periodic outpatient visits and his therapy could not be modified. Nevertheless, the therapy controlled his viraemia effectively. However, it may have favoured the onset of the adverse event; in fact, zidovudine is the drug with the highest risk of mitochondrial dysfunction and rhabdomyolysis.^8,9

Finally, in a patient, such as ours, with HIV infection complicated by premature coronary artery disease, ¹⁰ statin therapy should have been administered, but we preferred not to because of the episode of rhabdomyolysis. When commencing statin therapy in such patients, one should always keep in mind the pharmacokinetic interactions of PIs with cytochrome P450 3A4 ¹¹ to reduce the risk of rhabdomyolysis.^12–14

To exclude the presence of coronary artery disease, tests that require the use of iodinated X-ray contrast media are frequently necessary. To reduce the risk of lactate acidosis (5.1 per 1000 patient-years on cART ¹⁵ ) favoured by NRTIs, one should administer 7 mL/kg of normal saline solution to prevent contrast-induced nephropathy. Temporary discontinuation of NRTIs should also be contemplated, as is the case with metformin. This is particularly recommended in the presence of signs attributable to NRTI-induced mitochondrial dysfunction or lactic acidosis such as muscle soreness, fatigue, low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea or elevated CK, aminotransferases or serum lactate. ¹⁵