1

Case presentation

The patient is a 50-year-old African American female with a history of non-ST segment elevation myocardial infarction 15 months prior to this event. At that time, she underwent coronary angiography and was found to have single-vessel coronary artery disease with a 90% mid left anterior descending (LAD) coronary artery stenosis and significant disease in a second diagonal branch. Her left ventricular ejection fraction was mildly decreased at 45% with apical hypokinesis. She was treated with a 2.5×28 mm sirolimous drug-eluting stent in the mid LAD, which was post-dilated to 3 mm in the mid segment and 3.5 mm at the proximal edge with a noncompliant balloon. This was followed by balloon angiogplasty of the second diagonal branch 4 days later due to recurrent angina. Intravascular ultrasound (IVUS) of the LAD stent during her second procedure revealed a well-apposed and well-expanded stent in the mid LAD. She received clopidogrel for 12 months in addition to aspirin, simvastatin, metoprolol and lisinopril. She had been stable from the cardiac standpoint since then. On the day of her admission, she was exposed to carbon monoxide while she was working at an industrial plant. This was due to a carbon monoxide leak, affecting her and several of her coworkers. She complained of headache, lightheadedness, nausea and vomiting followed by a syncopal episode. Emergency medical services were activated by calling 911. The paramedics found her alert and oriented with a heart rate of 56 beats per minute and a blood pressure of 84/60 mmHg. She complained of sudden-onset retrosternal pressure-like chest pain, with an intensity of 10 (out of 10), accompanied by dyspnea. She was brought to Henry Ford Hospital. On arrival to the emergency room, her vital signs were as follows: heart rate, 56 beats per minute; blood pressure, 88/48 mmHg; respiratory rate, 20 breaths per minute; temperature, 96.8°F; oxygen saturation, 97% on 2 l of oxygen per minute via nasal cannula. The rest of her physical exam was unremarkable. The arterial blood gas revealed the following: p O ₂ , 172 mmHg; oxygen saturation, 99%; p CO ₂ , 44 mmHg; pH 7.25. The carboxyhemoglobin level was 21.2%. The initial troponin I was 6.23 ng/ml and the creatine kinase-MB was 38.5 ng/ml. The leukocyte count was 27,600/μl. The rest of her blood count and chemistry values were within normal limits. The 12-lead electrocardiogram revealed sinus bradycardia at a rate of 56 beats per minute and 3 mm ST elevation in anterior leads. She received oxygen at a 100% FiO ₂ via a non-rebreather mask for treatment of acute carbon monoxide poisoning and was transferred to the cardiac catheterization laboratory for primary angioplasty due to acute anterior ST segment elevation myocardial infarction. The coronary angiography revealed stent thrombosis in the mid LAD causing 100% occlusion ( Fig. 1 ). She underwent successful balloon angioplasty with a 3.5-mm noncompliant balloon within the stent ( Fig. 2 ). IVUS of the mid LAD stent revealed a well-apposed and well-expanded stent during her prior coronary intervention. There were no other lesions noted during this procedure. A two-dimensional echocardiogram revealed an ejection fraction of 20–25% with severe hypokinesis of all mid to distal segments. She remained hemodynamically stable and was transferred to the medical intensive care unit to continue treatment for acute carbon monoxide poisoning. Her treatment consisted of oxygen therapy using a non-rebreather mask. No hyperbaric chamber was used. The subsequent medical treatment for myocardial infarction included abciximab for 12 h, aspirin, clopidogrel, simvastatin and metoprolol. Lisinopril was not resumed due to low blood pressure. She had a good response to medical treatment for carbon monoxide poisoning as well as myocardial infarction. The troponin I peaked at 33.19 ng/ml and the creatine kinase-MB peaked at 194.4 ng/ml, which resolved during the hospitalization. She remained asymptomatic and hemodynamically stable from the cardiac standpoint and was discharged home in 5 days.

Stent thrombosis causing 100% occlusion of the mid LAD artery.

Left: Balloon angioplasty of the mid LAD. Right: Final angiography after balloon angioplasty reveals a patent LAD stent with normal flow.

2

Discussion

To our knowledge, this is the first reported case of carbon-monoxide-poisoning-induced late stent thrombosis. Multiple other cardiac harmful effects have been described but have not included late stent thrombosis.

Carbon monoxide poisoning can cause myocardial ischemia and infarction even in the absence of significant coronary artery disease . Various mechanisms have been proposed. Carbon monoxide competes with oxygen for hemoglobin, and its affinity for hemoglobin is 200–250 times greater than that for oxygen, causing a leftward shift in the oxygen–hemoglobin dissociation curve . This binding of carbon monoxide to the hemoglobin molecule causes alterations in the hemoglobin molecule, preventing oxygen from being released easily, which causes a reduction in oxygen delivery to the tissues, resulting in tissue hypoxia . Carbon monoxide may also bind to proteins, including myoglobin and cytochrome c oxidase . It has been found to bind to myoglobin in cardiac and skeletal muscles at carboxyhemoglobin levels of <2%, further interrupting muscle oxygen transport, causing hypoxia . It may bind cytochrome c oxidase, which is an enzyme in the mitochondrial electron-transport system chain that produces ATP by catalyzing the reduction of oxygen to water . The altered mitochondrial function secondary to hypoxia results in temporary contractile dysfunction of myocardial cells . Other mechanisms of cell death secondary to carbon monoxide poisoning are oxygen radical formation and subsequent lipid peroxidation along with induction of cellular apoptosis by nitric oxide secondary to high carbon monoxide levels .

Carboxyhemoglobin also affects coronary perfusion. A study by Ayres et al. found that increased levels of carboxyhemoglobin saturation of 9% for 30–120 s in the absence of coronary disease resulted in increased coronary blood flow, increased myocardial extraction ratio and a decrease in coronary sinus oxygen tension .

Carbon monoxide poisoning can cause microscopic cardiomyocyte structural changes as well. Tritapepe et al. evaluated the structural changes in a 25-year-old female with heart failure from carbon monoxide poisoning. Normal coronary arteries were documented by angiography. Endomyocardial biopsy was obtained. The electron microscopy findings revealed swollen mitochrondria, slight intracellular edema with occasional focal abnormal mitochondria and large deposits of glycogen in myocardial cells. The glycogen deposits were suspected to be secondary to hibernating myocardium since there was no history of chronic disease (myocardiopathy, congenital cardiopathy or glycogenosis). They found decreased uptake in a Tc sestaMIBI scintigraphy despite normal coronary arteries, indicating stunned myocardium likely secondary to mitochondrial impairment .

Another important pathogenic effect of carbon monoxide poisoning is the increased thrombotic tendency secondary to endothelial damage, increased platelet stickiness and alterations of the fibrinolytic pathway. The increase in viscosity and polycythemia are likely to contribute to acute myocardial infarction in the presence of normal coronary arteries and have been proposed as potential mechanisms . We suspect that this mechanism might have been the most important contributing factor in this particular case. An additional potential explanation is the fact that the patient received clopidogrel for 12 months only and had discontinued clopidogrel 3 months prior to the event. It is possible that the late stent thrombosis could have occurred due to the lack of clopidogrel alone, and the carbon monoxide poisoning could have aggravated an already formed thrombus. We suspect that carbon monoxide poisoning played a crucial role either by precipitating the thrombus formation or by aggravating an existing thrombus.