Case Report: Refractory Shock due to Fulminant Dengue Myocarditis Treated with Venoarterial Extracorporeal Membrane Oxygenation: A Report of Four Cases

INTRODUCTION

The incidence of dengue has increased 30-fold in the past five decades, with outbreaks occurring in some parts of the world. ¹ Disease can affect anyone, even young people without comorbidities. ²

Severe dengue has a wide range of clinical presentations and represents 1–2% of all dengue cases. ³ Despite WHO recommendations for diagnostic, treatment, prevention, and control of dengue, severe ⁴ and even fatal forms are more and more reported. ⁵ Recent literature showed that secondary infections and serotype 2 of dengue are more frequently associated with severe forms. ⁶

Dengue with myocarditis has been considered as usually uncommon. ⁷ Yet, during the recent outbreak in China in 2014, the prevalence of myocardial failure in dengue hospitalized patients was 11.8%. ⁸ More and more cases of dengue myocarditis are being described in the literature, with some fatal cases. ^9–12

Here, we describe the first case series of four autochthonous adult cases suffering from fulminant dengue myocarditis with refractory cardiogenic shock to be treated with extracorporeal membrane oxygenation (ECMO), and reviewed the literature.

CASE 1

In December 2018, a 47-year-old female patient with no comorbidity was admitted to the general hospital of Reunion Island for dyspnea. On admission, the patient had tachycardia of 140 beats per minute (bpm) and no detectable arterial pressure. The blood sample revealed a lactate level of 13.4 mmol/L, high-sensitivity (hs) troponin I of 8,257 ng/L, brain natriuretic peptide (BNP) of 2,935 pg/mL, a hemoglobin level of 14 g/dL, and platelet count of 70 G/L. The electrocardiogram showed sinus rhythm and general ST segment (EKG portion between S wave and T wave) elevation. The chest radiography showed bilateral interstitial infiltrates. The transthoracic echocardiography found left ventricular dysfunction with left ventricular outflow time–velocity integral (LVOF VTI) of 4 cm (for a lower standard of 16 cm) and left ventricular ejection fraction (LVEF) less than 10%. A diagnosis of cardiogenic shock was made, and the patient was transferred to the intensive care unit (ICU) with dobutamine and norepinephrine introduced. The patient’s hemodynamic status rapidly deteriorated despite vasoactive drugs, requiring femoro-femoral venoarterial (VA) ECMO, intra-aortic balloon pump (IABP), and mechanical ventilation. A coronary artery angiography found no abnormality. On day-1, peripheral ECMO was changed to central ECMO with left ventricular decompression through a third apical cannula, because of thrombosis of left ventricular outflow tract, as shown in Figure 1. Hemorrhagic shock occurred, requiring multi-transfusion in the first 48 hours.

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Case 1 echocardiography. (A) Thrombosis of left ventriclar outflow tract. (B) Thrombosis forming under the aortic annula. (C) Complete aortic valve closure, thrombosis of sinus of Valsalva. (D) Ejection fraction less than 10% and pericardial effusion on apical four chamber view.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 2; 10.4269/ajtmh.20-0372

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The patient evolved favorably: dobutamine was stopped on day 1 and norepinephrine on day 5. Despite a decrease in thrombocytopenia to around 50 G/L, continuous infusion of unfractioned heparin was maintained with no significant hemorrhage. On day 4, ECMO was successfully removed with a LVEF of 40%. The patient was weaned from mechanical ventilation on day 14 and left the ICU on day 16. Follow-up by cardiologic physicians showed complete myocardial recovery on day 26.

Etiologic searching found positivity for dengue type 2 at serum reverse transcriptase (RT)-PCR (Nucli Sens easyMAG, Biomerieux, NJ). Plasma serological tests for dengue (dengue virus IgG and IgM Capture DxSelectTM ELISA; FOCUS Diagnostics, Cypress, CA) confirmed primary infection. Myocardial biopsy showed inflammatory signs but no cytopathogenic effect and no gigantic cells. A myocardial magnetic resonance imaging performed on day 24 showed acute myocarditis with contrast linear enhancement in lateral basal and median areas and with subnormal cardiac function (Figure 2).

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Case 1 magnetic resonance imaging. Contrast linear enhancement in lateral basal and median areas (arrow markers).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 2; 10.4269/ajtmh.20-0372

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CASE 2

A 29-year-old man suffering from type 2 diabetes and obesity presented at the emergency department on April 2019 because of suffering from headache, stomach pain, and vomiting. Once admitted, he had hypotension of 79/41 mmHg and tachycardia of 110 bpm. The body scan showed scattered hypoperfusion signs. Norepinephrine was introduced, and the patient was transferred to the ICU because of persistent hypotension despite crystalloid infusion. Biologic tests found metabolic acidosis with pH of 7.21, lactate level of 11.9 mmol/L, thrombopenia at 11 G/L, hemoglobin level of 17 g/dL, and hs troponine I of 126 ng/L. The treatment was implemented by general anesthesia, mechanical ventilation, massive crystalloid fluid infusion, increasing norepinephrine, continuous hemofiltration, blood cell, and platelet transfusions. Second, echography was performed and showed biventricular severe dysfunction. Implantation of peripheral ECMO as salvage measure for refractory shock with cardiac dysfunction was decided at hour 16. Unfortunately, the patient died at hour 18 with severe plasma leakage.

Among etiologic screening, we only found positivity for dengue 2 by plasma RT-PCR (NucliSens easyMAG BIOMERIEUX, Durham, NC). Serologic test found dengue reactivation or primary infection (Dengue Virus IgM/IgG Capture DxSelect ELISA; FOCUS Diagnostics, Cypress, CA). Afterward, we found the patient’s past of dengue fever few years before.

CASE 3

On May 2019, a 63-year-old woman, smoker with past of splenic venous hematoma, suffered from fever and stomach pain. An abdominal scanner showed stability of the splenic hematoma but pericardial effusion. Pericardial effusion was found to be moderate at echocardiography, without compressive signs and normal myocardial function. A serologic test for dengue was found positive. On day 10, she was admitted at hospital because of dyspnea worsening. The patient arterial blood pressure was of 87/58 mmHg, tachycardia of 109 bpm, and pulse oximetry of 91%. There were bilateral interstitial opacities at chest radiography. Electrocardiogram showed sinus tachycardia without other abnormalities. The hs troponin I level was of 1,0251 ng/L and BNP of 784 pmol/L. Echocardiography revealed left myocardial dysfunction with LVOF VTI of 8 cm and LVEF of 10%. As the patient arrived for coronary artery angiography processing, a cardiac arrest occurred with electromechanical dissociation. She recovered after 15 minutes of resuscitation and was implanted with peripheral VA-ECMO and IABP. Angiography was found to be normal. Echocardiography showed almost complete loss of contraction. Organ deficiencies begin to decrease under ECMO support. Extensive testing revealed only positivity for dengue type 2 on serum RT-PCR and serologic test. The patient was negative for immunologic origin of thrombosis.

On the following 7 days, the myocardial state was stagnant. The IABP was complicated with leg ischemia which required the device removal. Computed tomography at day 6 found several cerebral and digestive ischemias. The patient died on day 7.

CASE 4

On March 2020, a 52-year-old man without any comorbidities presented at emergency for vomiting, diarrhea, and fever with a 3-day duration. On admission, the patient had tachycardia of 105 bpm and hypotension of 95/70 mmHg. Biological sample found pH of 7.35, lactate level of 4.2 mmol/L, thrombopenia of 129 G/L, hemoglobin level of 18 g/dL, and hs troponine I of 677 ng/L. Electrocardiogram showed no significant anomalies. A thoraco-abdomino-pelvic tomodensitometry was found to be regular. Echocardiography showed severe dysfunction with LVEF of 25%, LVOF VTI of 8 cm, and moderate pericardial effusion. Hemodynamic state decreased, and the patient was transferred to the ICU with diagnostic of cardiogenic shock. Dobutamine and norepinephrine were introduced at increasing doses. The patient required mechanical ventilation and VA-ECMO with IABP as cardiogenic shock became refractory. During the first 24 hours, the patient required 8 L of crystalloids infusion and transfusion of platelet because of thrombopenia of 69 G/L. There was no need in red blood cell. Diagnostic of dengue was made by RT-PCR. All other etiologies were found negative. The patient’s condition improved from day 5. Dobutamine and norepinephrine were stopped. As myocardial function recovered at day 7, VA-ECMO and IABP were removed. The patient was weaned from mechanical ventilation only at day 13 because a healthcare associated pneumonia associated with lung edemas. He was discharged from intensive care on day 17.

DISCUSSION

Myocarditis is an emerging form of severe dengue. Knowledge of this form is insufficient among medical community, and the management is still not well established. Ours is the first adult case of fulminant dengue myocarditis to be successfully treated with VA-ECMO, despite challenges in managing thrombotic and hemorrhagic complications (summarized in Table 1).

The diagnosis of fulminant dengue myocarditis should be considered when a patient suspected for dengue presents with congestive symptoms. According to European Cardiologic Society guidelines, diagnosis should be supported by electrocardiogram, troponin and BNP plasmatic levels, and echocardiography. ^13,14

Physiopathology and clinical course of dengue myocarditis are poorly known. ^11,15 A recent review of arbovirus infections found similarities between chikungunya and dengue. ¹⁶ Three outcomes are supposed to occur: full recovery, partial reversion, or death. ¹⁷ Long-term prognostic of fulminant myocarditis has been shown to be excellent among survivors. ¹⁸

The management of dengue fulminant myocarditis is challenging, especially during the critical phase because of plasma leakage and hemorrhagic events. A treatment proposed for refractory cardiogenic shock in reference centers is VA-ECMO. ¹⁹ Literature reviewing showed feasibility of veno-venous ECMO in acute respiratory distress syndrome in dengue. ²⁰ Only two cases of VA-ECMO being successfully used in children are described, but none among adult population. ^21,22 This circulatory support requires technical expertise and has significant morbi-mortality, including hemorrhagic complications. ^23,24 Despite increased hemorrhagic risk in dengue, ²⁵ case numbers 1 and 4 indicate that VA-ECMO is feasible in dengue.

Case number 2 died because of severe vasoplegic shock, which made ECMO management really difficult, but not because of hemorrhagic events. The medical state of case 3 was stabilized during few days on VA-ECMO, but the patient died because of ischemic adverse events of both the devices.

Since the beginning of 2018, Reunion Island has been faced with a dengue epidemic, with more than 25,000 serologic confirmed cases, including 738 (3%) hospitalized patients and 20 (0.1%) fatal cases. ²⁶ Recent epidemiologic reports show that the number of dengue cases increased markedly in 2019. In addition to the serotype 2 of dengue usually found, serotypes 1 and 3 have been recently identified on the local population. Severe forms might become more encountered. ^27,28 Dengue is a major public health concern, all the more so because no specific treatment is available at present. Dengue myocarditis is not rare, possibly underdiagnosed and potentially life threatening.

Our center experience showed that VA-ECMO support is feasible and could help to survive in cases of dengue fulminant myocarditis with refractory cardiogenic shock. Given the exponential rise in the number of dengue cases worldwide, ECMO may be increasingly required, and further studies are needed. Countries with access to ECMO support may already consider this device in case of cardiogenic shock in dengue.

Consent of patients 1 and 4 were given for this publication. For deceased patients, close family members give their consent.

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