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

Abstract

Kounis syndrome (KS) is a well-documented hypersensitivity vasospastic reaction induced by a variety of triggers. Clinical presentation ranges from non-specific symptoms such as dizziness and nausea to myocardial infarction. Many cases of KS were reported after the use of iodinated contrast media, mainly during radiological procedures. This report describes the case of a 46-year-old man developing coronary vasospasm and anaphylactic shock at the end of percutaneous coronary intervention. Occurrence of such pathology while performing coronary angiogram is a tricky situation for the invasive cardiologist. It requires recognising a rare syndrome and interrupting the procedure to avoid extra use of contrast media even in presence of severe coronary lesions due to vasospasm. Every interventionalist should be aware of such a presentation to recognise and react promptly when facing a potentially 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).

Figure 1.

Pre-PCI/and immediate post-PCI (two DES in LAD) coronary angiogram. PCI, percutaneous coronary intervention; DES, drug-eluting stent; LAD, left anterior descending artery; RCA, right coronary artery.

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.

Figure 2.

Kounis syndrome with initial occlusion of LAD and stenosis MA branch (B). Residual spasms after rewiring LAD (D). Good end result in LAD (E) but residual spasm in MA branch (F). DES, drug-eluting stent; LAD, left anterior descending artery; OM, obtuse marginal branch; PCI, percutaneous coronary intervention; ST, stent thrombosis.

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.

Discussion

Include a very brief review of similar published cases

KS is a relatively new entity in the field of medicine. Awareness arises worldwide but the knowledge regarding this syndrome relies almost only on case reports. Several settings and triggers have been described to date, followed by widely different outcomes. We underline the reports of cases related to contrast media (gadolinium or iodinated) some even leading to cardiac arrest.

From a physiological standpoint, the mechanism involving immune mediators in coronary syndromes is under research and currently not fully understood. KS might be an opportunity to better understand the link between these entities even though it does not offer to this day sufficient understanding to be clinically relevant.

From a clinical standpoint, this case-report emphasise the need for increased awareness of this not-so-rare syndrome. There are no guidelines for the treatment of KS but it is commonly admitted that standard antianaphylactic regimen and targeted coronary diagnosis and treatment is efficient.^{11 12} Like in this example, antihistaminic and corticosteroid drugs are the cornerstone in the treatment of anaphylactic reaction including KS. The addition of percutaneous cardiologic diagnostic and treatment may be also recommended.

Overall, early recognition is of the essence to improve outcome by diminishing exposure to the allergen and providing emergency targeted treatment. Increased awareness of emergency and invasive practitioners for this syndrome seems the first step in improving outcomes.

Patient’s perspective.

Before procedure, I felt rested and relaxed. I was admitted being trustful and feeling well.

During procedure, I continued to feel fine, surrounded by a friendly staff that explained every step of the procedure in a simple and understandable fashion. I felt well taken care of, even though while looking at the screen I didn’t understand quite much of details of the procedure.

After a while, I felt a pain in my right arm later irradiating in my chest. Up to this point I used to feel the motion of catheters in my arm but without pain, just a feeling. This new sensation became more and more intense and I began to feel tingling sensations in my limbs. A began to feel hot as well in my limbs first then in my whole body while I tried to concentrate on my breathing to forget the pain I was experiencing.

At this point, the pain was barely bearable. Everything surrounding me felt fuzzy, like a whirlwind of echoes and voices. I felt like every part of my body including my face was burning and I was nauseated. After that I felt like drained of all forces and couldn’t really remember what happened.

I can remember I was then transferred to the ICU where I regain gradually my calm and faculties. Overall, I didn’t feel much stressed out during all this time. I left the hospital the next day feeling great, full of energy.

I had to come back a few days later for a pain in my right arm where the procedure took place, was given medications and the pain left during the following 24 hours.

I’d like to specify that I had the feeling of being take care of by a skillful and thoughtful medical staff. I got answers to any questions with simple and understandable explanations. My fears were addressed to and led to a feeling I was well cared for. I emphasise this point because it feels to me such a care is the way to a positive outcome.

Learning points.

• Kounis syndrome is an unfrequent hypersensitivity reaction causing cardiac involvement ranging from angina pectoris to cardiac arrest.

• Many triggers have been reported including food, insect stings, material (latex) or drugs.

• Trigger avoidance and antianaphylactic treatment are recommended. Invasive cardiological diagnosis and treatment should be considered.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s)