Emergency. 2018; 6 (1): e9 CA S E RE P O RT Methamphetamine-Induced Cardiomyopathy (MACM) in a Middle-Aged Man; a Case Report Zulfiqar Qutrio Baloch1∗, Muhammad Hussain2, Shabber Agha Abbas2, Jorge L. Perez1, Muhammad Ayyaz1 1. Department of Internal Medicine, Brandon Regional Hospital, Brandon, Florida, USA. 2. R-Endocrinology, Hamilton, New Jersey, USA. Received: December 2017; Accepted: December 2017; Published online: 20 January 2018 Abstract: The development of methamphetamine-associated cardiomyopathy (MACM) represents a severe complication of chronic methamphetamine abuse. MACM-induced irreversible structural and functional changes in the heart can eventually lead to decompensated heart failure, ultimately requiring heart transplantation. In this case re- port we present a 47-year old male with a previous history of chronic amphetamine abuse who presented to the emergency room with severe dyspnea at rest associated with mild substernal non-radiating chest pain. He denied any previous cardiac history but had a positive urinary toxicology for methamphetamine. A complete cardiac workup ruled out all other etiologies. The patient required a 3-week intensive pharmacotherapy inter- vention to stabilize acute heart failure symptoms. At discharge he was classified as having New York Association Class III (NYHA-III) heart failure. His medical symptoms did not improve and he was considered for heart trans- plantation. With the increase in availability and abuse of methamphetamine, case of MACM such as ours are more frequently being encountered in the emergency departments. In addition to raising awareness, our case provides an outline of how MACM patients likely may present and the subsequent morbid sequela. Clinicians should maintain a high degree of suspicion when assessing all patients with a history of methamphetamine abuse. Early cardiac evaluation can help identify ventricular compromise in asymptomatic patients providing an opportunity to intervene prior to the development of irreversible MACM. Keywords: Methamphetamine; Cardiomyopathies; Emergency Service, Hospital © Copyright (2018) Shahid Beheshti University of Medical Sciences Cite this article as: Qutrio Baloch Z, Hussain M, Agha Abbas Sh, L. Perez J, Ayyaz M. Methamphetamine-Induced Cardiomyopathy (MACM) in a Middle-Aged Man; a Case Report. Emergency. 2018; 6 (1): e9. 1. Introduction Methamphetamine is a highly addictive central nervous sys- tem (CNS) stimulant produced from the parent compound amphetamine, which is frequently used to treat attention deficit hyperactivity disorder. Methamphetamine and re- lated compounds are frequently abused as recreational drugs, and are the second most widely used illicit drug in the United States after cannabis (1). Apart from CNS stimulation, methamphetamine has significant adverse effects on the peripheral nervous system associated with both short-term and long-term usage. The primary mechanism of action of methamphetamine is the increased release and decreased ∗Corresponding Author: Zulfiqar Qutrio Baloch, MD, PGY 2, Department of Internal Medicine, Brandon Regional Hospital, 119 Oakfield Dr, Brandon, FL 33511, USA. Email: zulfiqar.qutrio@gmail.com Tel: 813-916-5551, Fax: 813- 916-2944 uptake of catecholamines at the neuronal synapse produc- ing a marked effect on the cardiovascular system. Common physical symptoms after acute intoxication are chest pain, hypertension, arrhythmias, myocardial infarction, and pal- pitations (2). Chronic methamphetamine abuse can lead to development of severe cardiovascular complications such as coronary artery disease, acute myocardial infarction, ischemic cardiomyopathy, methamphetamine-associated cardiomyopathy (MACM), aortic dissection, malignant hy- pertension, dysrhythmias, and sudden cardiac death (3, 4). We discuss the case of a patient with dyspnea at rest due to severe cardiomyopathy following three years of metham- phetamine use. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Z. Qutrio Baloch et al. 2 2. Case presentation: A 47-year-old male presented to the emergency department with a chief complaint of severe dyspnea at rest associ- ated with mild substernal non-radiating chest pain. He de- nied palpitations, productive cough, abnormal sound while breathing, difficulty swallowing, history of a cardiac problem, recent viral illness, recent travel history, or any recent expo- sure to anyone having a similar presentation. His past med- ical and surgical histories were not significant. Family his- tory was not significant for cardiomyopathy. Upon urinary drug screening his test was positive for methamphetamine use. He stated that he had been using methamphetamine for the past three years. He denied use of any other recreational drugs and denied excessive alcohol use. On physical examination he was found to be alert and ori- ented to time, place, and person. Vital signs on presenta- tion were: blood pressure: 90/70 mmHg, pulse rate: 120 beats/minute, and respiratory rate: 26 breaths/minute. Ar- terial oxygen saturation was 88% in room air. Examination of the chest revealed bilateral diffuse crackles, most pro- nounced on lung bases. A chest radiograph showed pul- monary congestion and cardiomegaly. An electrocardio- gram (ECG) showed sinus tachycardia, low voltage, poor pro- gression of R-wave in precordial leads, incomplete LBBB, extreme right axis deviation with RV strain, S1 Q3 inverse T3 pattern, Q-wave in 2-3 AVF suggestive of old MI (Fig- ure 1). Cardiac troponin testing was within reference range. To further narrow down the differential diagnosis a com- plete work-up was ordered including: complete blood count (CBC), basic metabolic profile (BMP), lipid profile, thyroid function tests, creatinine phosphokinase, erythrocyte sedi- mentation rate (ESR), blood morphology, liver function test (LFT), protein level, and iron studies. These were all found to be within reference range. Moreover, immunological as- says [immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-Epstein–Barr virus] and toxoplasmosis serology were found to be negative. Fasting transferrin saturation test was normal. Transthoracic echocardiography (TTE) revealed se- vere left ventricular (LV ) and left atrial (LA) dilatation, ex- tremely impaired systolic function with left ventricular ejec- tion fraction (LVEF) below 15% (actual was 8%), full size RV, normal mitral and aortic valve, normal aortic root size (Fig- ure 2). Subsequent coronary angiography testing found no coronary artery disease. Treatment for acute heart failure exacerbation was imme- diately initiated including use of lisinopril, carvedilol, and furosemide. Following three weeks of intensive pharma- cotherapy and considerable clinical improvement the patient was discharged from the hospital. At time of discharge the patient was classified as having New York Heart Association Class III (NYHA-III) heart failure. Outpatient follow-up visits Figure 1: 12 leads electrocardiography of the patient. Figure 2: Transthoracic echocardiography of the patient (paraster- nal long axis view). were scheduled at 1, 2, and 3 months, respectively. No clin- ical or echocardiographic improvements were noted during all follow-up visits. After optimal medical treatment the pa- tient’s symptoms were not improved and he was considered for heart transplantation. 3. Discussion The incidence of methamphetamine abuse among young population has increased with predominance among col- lege students in the United States (5). There are several reasons behind this increased frequency. One explanation is the relatively easy availability and access through the In- ternet as depicted in the World Drug Report 2016 (1). An- other reason is the inexpensive pricing making it a suitable drug of choice even for those with economic constraints. As an agent having a long duration of action it holds a particular appeal for those desiring chronic stimulant ef- fects (1). Methamphetamine can be ingested orally, smoked, snorted, or injected. Smoking or injecting the drug pro- duces an immediate effect and makes the patient prone to developing adverse health problems, while raising the addic- tion potential. Methamphetamine has good lipid solubility compared to its parent compound, amphetamine, and can This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2018; 6 (1): e9 more readily cross the blood brain barrier. The drug has a marked effect on both central and peripheral nervous sys- tems. By facilitating increased release and decreased reup- take of catecholamines from nerve terminals, it stimulates alpha- and beta-adrenergic receptors. The pronounced ef- fects of the drug are on multiple organ systems including the cardiovascular system leading to hypertension and tachycar- dia in the short-term and severe cardiovascular complica- tions such as myocardial infarction, dysrhythmias, ventric- ular hypertrophy, pulmonary edema, hypertension, cerebral stroke, cerebral hemorrhage, seizures, psychosis, and in cer- tain cases even death. Acute coronary syndrome can also be a result of cardiac damage as evident by published case reports on acute coronary syndrome and coronary artery rupture following drug abuse (6, 7). The prevalence of methamphetamine-induced heart failure is also consider- able, with at least one study reporting an up to 5% incidence rate in patients presenting to the emergency department with heart failure (8). A recent article pointed out that the experience of emergency health care personnel, especially mental health professionals, in dealing with patients pre- senting with acute methamphetamine abuse is quite com- plex. They have to employ a range of different strategies to stabilize patients who are acutely engaged in hyperactive and stimulant behavior (9). The development of cardiomyopathy is a severe complica- tion of chronic methamphetamine abuse and is rarely a sign of acute abuse. In a study on 107 young patients present- ing with idiopathic cardiomyopathy, 40% of patients were found to have chronically abused methamphetamines in subsequent interviews and urinalyses (3). Our patient pre- sented with severe dyspnea at rest and on further investi- gation was found to have severe systolic dysfunction due to cardiomyopathy following three years of chronic metham- phetamine abuse. Patients fitting this profile develop struc- tural and functional changes in myocytes such as atrophy, hypertrophy, eosinophilic degeneration, and fibrosis (10). Histopathological assessment is likely to reveal cardiomy- opathic lesions including slight interstitial fibrosis. These changes eventually lead to decompensated heart failure that requires heart transplantation for continued survival (8). Certain patients who achieve symptomatic relief with phar- macotherapy alone may benefit from biventricular cardiac pacing or automatic implantable cardiac defibrillators (4). The decision to pursue such interventions depends on many factors such as treatment compliance, likelihood of relapse, presence of co-morbidities, and risk of device infection, es- pecially in intravenous drug abusers (4). Schurer and col- leagues recently investigated the histopathological impact of methamphetamine discontinuation in chronic abuse pa- tients by following the clinical characteristics, histopatho- logical features, and clinical outcome in a cohort of 30 pa- tients presenting with MACM (10). Patients with LVEF <40%, whose endomyocardial biopsy confirmed MACM were fol- lowed for mean 35 ± 22 months post-study inclusion. They compared histopathology changes between those who dis- continued the drug and those who continued. Patients en- rolled in the study were highly symptomatic and 83.3% of them had New York Heart Association functional class III or IV dyspnea. The mean duration of methamphetamine abuse was 5.7 years. Baseline LVEF was 19 ± 6%. At follow-up, 23 patients had stopped taking methamphetamine whereas 7 continued. Those who continued had persistently, severely impaired LVEF and LV dilatation; whereas those who dis- continued had LV remodeling and improved LVEF. Discon- tinuation was also associated with improved symptoms. In terms of the primary endpoint of composite death, non- fatal stroke, and rehospitalization for heart failure, these events occurred more frequently in the group that contin- ued abusing methamphetamine (p=0.037). With respect to histopathologic changes, only fibrosis was found to be asso- ciated with the duration of methamphetamine abuse, occur- ring in a more severe form with longer abuse duration. No difference in inflammatory changes was observed between the 2 groups. Our patient had an LVEF of 8%, which is typ- ical as patients with MACM have a significantly lower LVEF compared to patients with cardiomyopathy from all other causes (3). In addition to that, our patient had no signifi- cant risk factors responsible for causing cardiomyopathy and heart failure, except for methamphetamine abuse. Patients with a modestly reduced LVEF may demonstrate a more se- vere ventricular dilatation than those with other causes of cardiomyopathy on imaging. MACM and its clinical sequela warrant attention, especially in an era of increasing use of methamphetamines and related compounds. Recognizing MACM and associated heart failure in the emergency set- ting is essential for initiating both short-term and long-term treatments, which hold implications for survival. 4. Conclusion: Methamphetamine-induced cardiomyopathy or MACM and its clinical sequela warrant attention, especially in an era of increasing use of methamphetamines and related com- pounds. Clinicians should maintain a high degree of suspi- cion when assessing all patients with a history of metham- phetamine abuse, especially chronic users and those who may have preliminary signs or symptoms of cardiovascu- lar compromise. In patients presenting with idiopathic car- diomyopathy, methamphetamine abuse should be in the dif- ferential diagnosis if the patient’s profile is suspicious. Early cardiac evaluation can identify ventricular compromise in asymptomatic patients prior to the development of MACM and should be considered for screening purposes. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Z. Qutrio Baloch et al. 4 5. Appendix 5.1. Acknowledgements The authors would like to thank the internal medicine department staff of Brandon Regional Hospital, Brandon, Florida, USA. 5.2. Authors contribution All authors passed four criteria for authorship contribution based on recommendations of the International Committee of Medical Journal Editors. 5.3. Conflict of interest None. 5.4. Funding None. References 1. World Drug Report 2016 [cited 2017 August 28]. 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This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com