Chloroquine poisoning-associated inverted Tako-tsubo cardiomyopathy

To the Editor:

Tako-tsubo cardiomyopathy, also called left apical ventricular ballooning syndrome, is a transient left ventricular (LV) dysfunction usually attributed to an acute stress situation, mimicking an acute coronary syndrome despite normal epicardial arteries.¹ LV shape in Tako-tsubo cardiomyopathy is described as looking like a Japanese fishing pot used for trapping octopuses, with a round bottom and a narrow neck. However, variants have been reported with right ventricular, mid-ventricular, or basal involvement, which are referred to as inverted Tako-tsubo cardiomyopathy. To our knowledge, inverted in contrast to typical Tako-tsubo cardiomyopathy echocardiography patterns² were rarely reported in poisonings.³

We report a 35-year-old woman with no past medical history who was referred to our intensive care unit 2 h after ingesting 7 g of chloroquine. Electrocardiogram revealed membrane stabilizing effects with QRS prolongation (0.136 ms). The patient was intubated and received fluids (3000 ml saline), 8.4% sodium bicarbonate (750 ml), epinephrine infusion (started at 0.5 μg/kg/min then progressively increased up to 3 μg/kg/min), and diazepam (4 mg/kg per day) within the first 3 h. Rapidly, she developed seizures requiring phenobarbital infusion (20 mg/kg) with the resolution of seizure-like activity assessed using electroencephalography. On presentation, blood sampling showed elevated troponin Ic (45 μg/l; reference range < 0.04) and chloroquine concentration (16.9 μmol/l; reference range < 6). Routine blood and urine toxicological screening including ethanol, acetaminophen, salicylates, benzodiazepines, cyclic antidepressants, phenothiazines, meprobamate, opiates, and cocaine was negative. Echocardiography showed inverted Tako-tsubo cardiomyopathy pattern with ballooning of the basal and mid-ventricular segments but normal apical contractions. Cardiac output measured using echocardiography was 2 l/min while receiving 0.5 μg/kg/min epinephrine. Emergent extracorporeal life support was surgically inserted due to refractory cardiogenic shock, allowing a rapid weaning of epinephrine infusion. However, heart function did not recover until the fourth day. At this stage, echocardiography showed a persistent marked inverted Tako-tsubo cardiomyopathy pattern with a LV ejection fraction of 25%. Subsequently, the patient developed multiorgan failure with disseminated intravascular coagulation, massive hemolysis, acute renal and liver failure, and pulmonary edema on day 1, resulting in brain death on day 4.

Many clinical situations including poisoning have been associated with Tako-tsubo cardiomyopathy;^2,3 however, there have been no previous reports of chloroquine toxicity associated with Taku-tsubo cardiomyopathy. Several hypotheses could be suggested to understand the relationship between chloroquine poisoning and Tako-tsubo cardiomyopathy. Usually, myocardial ischemia is the first mechanism proposed to explain Tako-tsubo cardiomyopathy. Consistently, mild coronary artery stenosis is frequent in the general population and may be present in up to 10% of Tako-tsubo cardiomyopathy patients.¹ However, our patient did not undergo a coronary angiography due to her hemodynamic instability as well as the very low suspicion of coronary disease. No coronary stenosis including right coronary artery and circumflex artery can explain the inverted Tako-tsubo cardiomyopathy pattern, although a possible metabolism/perfusion mismatch leading to myocardial stunning cannot be ruled out. In our patient, no post-mortem examination was performed to definitively confirm patent coronary arteries.

In relation to epinephrine, Tako-tsubo cardiomyopathy has been attributed to a change in the transduction pathway following catecholamine receptor stimulation with a molecular switch from the stimulatory alpha-subunit of the G protein called G(s) and linked to adenyl cyclase to the inhibitory subunit called G(i).⁴ Chlorquine-induced membrane stabilizing effect causes intense endogenous adrenergic release in response to ventricular conduction blockade. Catecholamine storm resulting from both chloroquine poisoning and its management based on epinephrine infusion may have played a significant role; however, a resulting typical Tako-tsubo cardiomyopathy pattern would have been expected, due to the apical repartition of catecholamine receptors in the LV, sparing the basal region.⁵

Finally, cardiac involvement is frequently associated with neurological impairment in the intensive care unit. Typically, Tako-tsubo cardiomyopathy patterns have been described during subarachnoid hemorrhage and status epilepticus.¹ Here, early chloroquine-induced seizures may have represented an additional neurological trigger of the inverted Tako-tsubo cardiomyopathy.

In conclusion, physicians should be aware of the possible development of Tako-tsubo cardiomyopathy pattern after chloroquine poisoning. The possible mechanisms for this include direct chloroquine toxicity, catecholamine infusion, myocardial ischemia, and seizures.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.