Acute right ventricular failure: a novel presentation of methadone-induced cardiotoxicity
- Mohamad Badie Taha 1,
- Osama Dasa 1,
- Mohammad Al-Ani 2,
- Omar B Taha 1,
- Nila S Radhakrishnan 1 and
- Mustafa M Ahmed 2
- 1 Division of Hospital Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
- 2 Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
- Correspondence to Dr Mohamad Badie Taha; mohamad.taha@medicine.ufl.edu
Abstract
As methadone use increases, the potential for methadone-induced cardiotoxicity (MIC) may rise. We describe a case of acute right ventricular (RV) failure leading to cardiogenic shock after methadone overdose. This presentation was followed by full RV recovery. This previously undescribed presentation highlights the challenges involved with MIC, its diagnosis and its management.
Background
Methadone is a widely used synthetic opioid in the management of opioid addiction and chronic pain. The increased use of methadone has resulted in an increased prevalence of its toxicity, particularly methadone-induced cardiotoxicity (MIC). Reported MIC includes conduction abnormalities, arrhythmias, cardiomyopathy and coronary artery diseases (CADs).1 In this report, we describe a patient who presented with acute and isolated right ventricular (RV) failure leading to cardiogenic shock after intentional methadone overdose. The pathophysiology leading to this, potentially fatal, cardiotoxicity of methadone is not fully understood. To our knowledge, acute RV failure is a novel presentation of MIC.
Case presentation
The patient is a 56-year-old woman with a medical history significant for chronic obstructive pulmonary disease, chronic hepatitis C infection, seizure disorder on levetiracetam and major depression, not on medical therapy. She was being treated with methadone (60 mg daily) maintenance therapy for opiate addiction and chronic back pain. She was witnessed by her husband to ingest a total of 2.4 g of methadone in a suicidal attempt at her home. As the paramedics arrived roughly 30 min after the witnessed overdose, the patient was unresponsive, pupils were pinpoint, Glasgow Coma Scale Score of 7, heart rate 96 beats per minute, blood pressure 101/69 mm Hg, respiratory rate 12 breaths per minute, oxygen saturation 96% and blood glucose level of 157 mg/dL. She was given a total of three doses of naloxone, 1.0 mg each, with no response, and underwent endotracheal intubation for airway protection. On arrival to the emergency department, her temperature was 36.1°C, heart rate 120 beats per minute, blood pressure 79/46 mm Hg, respiratory rate 16 breaths per minute and oxygen saturation 97%. On physical examination, she was unresponsive. Her skin was cold and mottled, and her jugular venous pressure was elevated 15 cm H2O above the sternal angle level. Peripheral pulses were regular but weak. Auscultation yielded normal heart sounds and clear lung fields bilaterally.
Investigations
Laboratory values were significant for elevated high-sensitivity troponin I value of 631 pg/mL, which peaked at 927 pg/mL, and B-type natriuretic peptide value of 428 pg/mL. Serum and urine drug screen was positive for methadone but negative for other opiates, cocaine and ethyl alcohol, and serum levetiracetam was within the therapeutic range. Arterial blood gas showed mild metabolic acidosis (pH 7.31, pCO2 31 mm Hg, and pO2 140 mm Hg), and infection workup was negative. X-ray of the chest was negative for any significant cardiopulmonary changes. CT angiography (CTA) scan of the chest showed mild dilatation of the right ventricle (RV) but no evidence of pulmonary embolism, dilatation of the pulmonary arteries or any other significant cardiopulmonary changes (figure 1). Although the study was not ideal, there was no suggestion of CAD. Serial ECGs showed sinus tachycardia and prolonged corrected QT (QTc) intervals, but no significant ischaemic changes (figure 2). The initial transthoracic echocardiography (TTE) showed dilated RV with severe systolic dysfunction and relative preservation of contractility at the apex compared with the basal segments. The tricuspid regurgitation doppler waveform was incomplete and not adequate for the estimation of the RV systolic pressure. The left ventricle (LV) size and ejection function were normal with no LV wall motion abnormalities (figure 3 and video 1). A TTE that was done 3 months before this presentation, for evaluation of atypical chest pain, did not show any LV or RV dilation or dysfunction or any evidence of elevated pulmonary artery pressure.
CT angiography scan of the chest. Images did not show pulmonary thromboembolism or any major cardiopulmonary changes. (A) No dilatation of the PA noted. PA diameter=26.9 mm, AA diameter=32.1 mm and PA/AA diameter ration=0.84. (B) Multiplanar reconstructed four-chamber view showing mid-level dilatation of the RV (mid-level RV diameter=37.1, mid-level LV diameter=36 mm and mid-level RV/LV diameter ration=1.03), but normal basal and longitudinal dimensions. AA, ascending aorta; LV, left ventricle; PA, pulmonary artery; RA, right ventricle.
Serial ECGs on presentation to the emergency department. (A) At the time of presentation, ECG showing sinus tachycardia, no ST-segment elevation, QTc 505 ms and (B) 1 hour after the presentation, ECG showing sinus tachycardia, no ST-segment elevation, QTc 530 ms. QTc, corrected QT interval.
Echocardiography on presentation to the emergency department showing dilated RV with severe RV systolic dysfunction and relative preservation of contractility at the apex, moderate tricuspid regurgitation and normal LV function with no regional wall motion abnormality. RV length=77.2 mm, RV basal dimension=31.2 mm, RV FAC=23.3%, TAPSE=12.3 mm, LV EF=55%. (A) Subcostal long-axis view during diastole. (B) Subcostal long-axis view during systole. EF, ejection fraction; FAC, fractional area change; LV, left ventricle; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion.
Differential diagnosis
A middle-aged woman presenting with methadone overdose, acute RV dysfunction, haemodynamic instability (ie, shock) and altered mental status. The differential diagnosis included acute myocardial infarction, acute respiratory failure, acute pulmonary embolism, acute intracranial pathology, sepsis and drug toxicity. CT of the head was negative for any intracranial abnormalities, CTA of the chest was negative for acute or chronic intrathoracic pathologies and no dilatation of the pulmonary artery, suggesting no chronic pulmonary hypertension. Arterial blood gas showed mild metabolic acidosis but no hypoxemia. Sepsis workup did not suggest any potential source of infection. All this workup excluded acute pulmonary process as the underlying aetiology of this presentation.
Concerning acute coronary syndrome (ACS) being a possible diagnosis due to haemodynamic instability, elevated cardiac enzymes and a new onset isolated and severe RV dysfunction, the patient did not have underlying cardiac risk factors, serial ECGs did not show any acute or chronic ischaemic changes, CTA of the chest was not suggestive of CAD and the RV systolic function recovered within few days. Therefore, no ischaemic cardiac workup was pursued during the hospitalisation period.
Finally, the patient had a normal TTE that was done 3 months prior to the current presentation. On admission, TTE showed isolated and severe RV dysfunction. After supportive care, TTE showed a complete resolution of the RV dysfunction. This all raised the possibility of atypical stress-induced cardiomyopathy due to methadone overdose.
Treatment
The patient was managed with intravenous isotonic fluid resuscitation (30 mL/kg), mechanical ventilation and vasopressor support (norepinephrine, the highest dose reached was 0.3 mg/kg/min). She gradually improved and was extubated on day 2. A repeat TTE on day 4 showed normalisation of the RV size and function (figure 4 and video 2).
Echocardiography on day 4 after stabilisation and recovery showed normal RV size and systolic function, mild tricuspid regurgitation and normal LV function. RVSP=30 mm Hg, RV length=69 mm, RV basal dimension=31.6 mm, RV FAC=35%, TAPSE=19 mm, LV EF=55%. (A) Subcostal long-axis view during diastole. (B) Subcostal long-axis view during systole. EF, ejection fraction; FAC, fractional area change; LV, left ventricle; RV, right ventricle; RVSP, right ventricle systolic pressure; TAPSE, tricuspid annular plane systolic excursion.
Outcome and follow-up
The patient was discharged home on hospital day 7 in a stable condition with instructions to follow-up as an outpatient. A follow-up TTE at 1 month post discharge revealed normal RV and LV size and function (video 3). A follow-up ECG showed normalisation of the QT interval.
Discussion
In this case report, we describe a novel presentation of MIC, leading to isolated and acute RV dysfunction after the ingestion of a hefty dose of methadone. The presentation was followed by a full functional recovery of the RV.
Acute RV failure syndromes are most often seen and well described in acute myocardial ischemia, pulmonary embolism, acute respiratory distress syndrome or following cardiac surgery. When the RV fails to produce sufficient output, the LV is underfilled, cardiac output falls and circulatory shock may follow, often abruptly. Other potentially fatal complications include life-threatening ventricular arrhythmias and RV thrombosis. TTE is exceedingly useful in recognising this problem.2 3 In our case, there was no evidence of ACS or pulmonary disease. The exact mechanism for RV dysfunction in methadone overdose is not fully understood. Previous case reports described stress-induced cardiomyopathy (Takotsubo syndrome) leading to left ventricular dysfunction, without any evidence of involvement of coronary arteries, in acute methadone poisoning4 5 and withdrawal.6 7 It is believed that stress-induced surge of hormones such as catecholamine, respiratory depression, and circulatory collapse cause microvascular dysfunction and myocardial stunning, leading to acute cardiomyopathy. Besides, methadone significantly increased mean arterial pressure, catecholamines and vasopressin concentrations.8 Full recovery of stress-induced cardiomyopathy is typically observed within a few days. In our case, complete recovery was observed on hospital day 4. The described clinical picture could represent an atypical presentation of stress-induced cardiomyopathy.
Biologic plausibility on methadone-related RV failure can be deduced from animal research. Experiments have shown that the use of higher doses of methadone resulted in higher mean pulmonary artery pressure.9 10 When pulmonary vascular resistance rises markedly, the RV dilates and thins, and the septum shifts towards the left. This all may lead to a decrease in cardiac output.3
Treatments of this potentially fatal condition are focused on optimisation of RV preload, afterload and contractility. When patients continue to deteriorate despite all medical efforts, mechanical support becomes the last therapeutic option. The most readily available forms of mechanical support are extracorporeal membrane oxygenation and RV assist device, which, luckily, were not needed in our case.3
In conclusion, in the recent era of the opioid epidemic, clinicians should be vigilant about the risks and benefits of methadone for the treatment of pain and opioid addiction to avoid catastrophic sequelae resulting from cardiovascular toxicity. MIC is a potential cause of isolated an RV dysfunction that is potentially life-threatening. This case highlights a new entity of MIC that should be further explored.
Learning points
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Isolated right ventricular (RV) dysfunction is a novel presentation of methadone induced cardiotoxicity.
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When clinicians prescribe methadone, they should be more vigilant about the potential cardiotoxicities of methadone, ranging from the asymptomatic prolongation of corrected QT (QTc) interval to sudden cardiac death.
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Clinicians should recognise methadone toxicity as a cause of acute and isolated RV dysfunction; a potentially fatal complication.
Footnotes
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Twitter @mohamadbtaha
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Contributors MBT, OD, OBT and NSR contributed to the article planning and conception. MBT, OD, MA-A and OBT contributed to the acquisition of data. MBT, OD, MA-A, OBT, NSR and MMA contributed to the analysis and interpretation of data. MBT, OD and OBT contributed to drafting the article. MA-A, NSR and MMA contributed to revising the article critically for important intellectual content. All authors approved the version submitted and agree to be accountable for the article and to ensure that all questions regarding the accuracy or integrity of the article are investigated and resolved.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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