Iodinated contrast media induced Kounis syndrome during coronary angiogram: a life-threatening clinical dilemma

Background

Kounis syndrome (KS) is an acute hypersensitivity reaction that is characterised by the activation and degranulation of mast cells and the presence of a cardiac event such as coronary vasospasm, stent thrombosis and myocardial infarction.1 2 The mediatory molecules released include histamine, proteases, arachidonic acid metabolites or platelet-activating factor. These molecules act as a trigger of several physiologic paths leading to vascular spasm and activation of the coagulation system.3 The KS has been described in a wide variety of allergic reactions, from contrast media, drugs to hymenoptera or snake bites.4–7

The prevalence of KS is estimated by 19/100 000 people, which represented 3.4% of the consultations for anaphylaxis in the ER department. Provided a lifetime incidence of anaphylactic reactions in the USA of 0.05%–2.0%, this syndrome is probably widely underdiagnosed.8 All physicians should be aware of this entity and trained to initiate proper treatment.

These considerations are of utmost importance for medical staff dealing with drugs and products that are known to trigger anaphylactic reactions and thus possibly KS. Clinical procedures involving the use of allergenic material—such as contrast, drugs or vaccine—could be harmful if exposure is sustained during a KS. Therefore, the staff should be attentive to discontinue the exposure of the potential trigger as soon as the signs and symptoms of KS happen.

Case presentation

A patient in his forties with no allergic history was referred to a coronary angiogram for de novo chest pain. The pain was systematically relieved by nitroglycerine. The radial coronary angiogram revealed a chronic total obstruction of the mid-left anterior descending (mid-LAD) coronary artery. A percutaneous coronary intervention (PCI) was performed and led to the implantation of two overlapping drug-eluting stents (2.5/28 mm and 2.25/20 mm, Synergy, Boston Scientific) with an initial good angiographic result (figure 1).

The patient then started reporting about paresthesia in the arms and legs. His heart rate rises from 68 to 118 bpm. Inspection of the skin does not show any erythema. No chest pain or dyspnoea. Given a drop in systolic pressure from 157 to 102 mm Hg, anaphylaxis was considered and an antiallergic medication with 125 mg of methylprednisolone and 2 mg of clemastine was administrated intravenously. Because of the paucity of symptoms and a persistent drop in blood pressure together with sinus tachycardia, we performed a transthoracic echocardiogram to rule out any mechanical complication related to the procedure. A bolus of 10 mg of intravenous ephedrine (Dilution of 1: 100 000 (0.01 mg/mL)) and 50 µg of intravenous epinephrine (Dilution of 1:100 000 (0.01mg/mL)) were administered. At this time, the patient reported chest pain and the echocardiography showed transient apical akinesia. This motivated to perform a new coronary angiography, which demonstrated occlusion of LAD. The artery was quickly revascularised with a semicompliant balloon (Sapphire II Pro 2.00-20 balloon, OrbusNiech) and an intracoronary infusion of nitroglycerin was started. A thigh residual stenosis was then treated by implantation of a third drug-eluting stent (3.00/08 mm, Synergy, Boston Scientific) (figure 2). Antiaggregating therapy with intravenous tirofiban was initiated. At this moment, a facial erythema appeared. The control angiogram showed a good result in LAD but new subocclusive stenosis of a marginal branch of the circumflex artery. We suspected a KS triggered by contrast media and the procedure was ended at this stage to minimise further. Due to spasms in the peripheral arteries, invasive pressure reading was not possible without a central measurement. Therefore, a pigtail catheter was left in the ascending aorta until haemodynamic stabilisation was achieved.

Investigations

The serum tryptase was 38 µg/L (normal value<13.5 µg/L) and high-sensitivity troponin peak was recorded at 32 ng/L (normal value<14 ng/L).

Differential diagnosis

The unusual course of this case started with paresthesia and sinus tachycardia at the end of PCI. At this stage, the differential diagnosis included, among others, anxiety, allergy, stroke or pericardial effusion. Alternatively, a coronary thrombosis, dissection or vasospasm could be responsible for the drop in blood pressure even without chest pain.

The appearance of chest pain modified the working hypothesis. At this stage, we performed echocardiography to exclude a cardiac tamponade but demonstrated a new impairment of left ventricular wall motion. This provided insight into a possible new coronary occlusion and motivated us to repeat a coronary angiogram.

After treating the stent thrombosis, we noted a spastic lesion in a previously healthy branch. This made us to suspect an allergic reaction to the contrast medium causing a KS. Elevated tryptase level later confirmed our working hypothesis of anaphylactic reaction causing the coronary involvement. We did not consider the metallic scaffolding of the stents to be the culprit in this case, provided only delayed hypersentivity reactions (type IV) were reported to date in the literature and the fact our patient showed no sign of anaphylactic reaction after discontinuation of the procedure without ablation of said stents.

The main challenges in diagnosing KS in this patient were the following:

• The patient had no history of allergy and was obese (body mass index 42 kg/m²), which delayed the appearance of visible skin erythema and made echocardiography difficult. Cardiac output diminution could also explain this delayed apparition of skin feature through lack of peripheral perfusion.9

• The initial vasospasm of LAD was considered to be induced by the procedure in the absence of evidence of multivessel vasospasm at the time.

• The onset of KS with occlusion of the LAD and subocclusion of the left circonflex artery added a cardiogenic component to anaphylactic shock.

• The spasms of the peripheral arteries did not make it possible to have a reliable measurement of the arterial pressure without a catheter in the ascending aorta.

Treatment

The main challenges in the treatment of KS in this case were as follows:

• Injections of contrast media-induced spasms but were necessary for the treatment of acute occlusion of the LAD. From then on, minimal injections were made and we opted to revascularise the arteries, but leave a final result with residual spasms in the other branches without further angiographic control.

• Although simultaneous anaphylactic shock required administration of vasoconstrictive amines, coronary spasms required administration of vasodilators.

• A few case reports demonstrate epinephrine-induced coronary vasospasms after treating drug-induced vasovagal reactions or allergic reactions. We only used minimal dosage of catecholamine, though it is possible it contributed to the initial worsening of the diffuse spasms.10

Outcome and follow-up

The clinical follow-up was simple with rapid mobilisation and hospital discharge after 12 hours. Corticosteroids and antihistamine were prescribed for 5 days. The patient presented later with right arm weakness due to radial artery thrombosis. Subsequently, he did not have any new symptom and underwent a complete allergic work-up with the eviction of Iomeprol.