Methamphetamine use and heart failure: Prevalence, risk factors, and predictors

doi:10.1016/j.ajem.2018.01.001

The American Journal of Emergency Medicine

Volume 36, Issue 8, August 2018, Pages 1423-1428

https://doi.org/10.1016/j.ajem.2018.01.001 Get rights and content

Abstract

Objectives

To compare methamphetamine users who develop heart failure to those who do not and determine predictors.

Methods

Patients presenting over a two-year period testing positive for methamphetamine on their toxicology screen were included. Demographics, vital signs, echocardiography and labs were compared between patients with normal versus abnormal B-type natriuretic peptide (BNP).

Results

4407 were positive for methamphetamine, 714 were screened for heart failure, and 450 (63%) had abnormal BNP. The prevalence of abnormal BNP in methamphetamine-positive patients was 10.2% versus 6.7% for those who were negative or not tested. For methamphetamine-positive patients, there was a tendency for higher age and male gender with abnormal BNP. A higher proportion of Whites and former smokers had abnormal BNP and higher heart and respiratory rates. Echocardiography revealed disparate proportions for normal left ventricular ejection fraction (LVEF) and severe dysfunction (LVEF < 30%), LV diastolic function, biventricular dimensions, and pulmonary arterial pressures between subgroups. For methamphetamine-positive patients with abnormal BNP, creatinine was significantly higher, but not Troponin I. Logistic regression analysis revealed predictors of abnormal BNP and LVEF < 30% in methamphetamine-positive patients, which included age, race, smoking history, elevated creatinine, and respiratory rate.

Conclusion

Methamphetamine-positive patients have a significantly higher prevalence of heart failure than the general emergency department population who are methamphetamine-negative or not tested. The methamphetamine-positive subgroup who develop heart failure tend to be male, older, White, former smokers, and have higher creatinine, heart and respiratory rates. This subgroup also has greater biventricular dysfunction, dimensions, and higher pulmonary arterial pressures.

Introduction

Methamphetamine was first synthesized in the early 20th century and marketed as a bronchodilator [1]. It was soon thereafter misused for various conditions, such as dieting and to increase wakefulness. Legal availability of methamphetamine ended in 1970, when it was designated as a controlled Schedule II drug. Methamphetamine faded from popularity until the late 1980s, when it reappeared in the western United States and Hawaii [2]. An increasing trend of methamphetamine-using patients presenting to emergency departments with chest pain, stroke, mental status change, skin infection, and traumatic injury was noted for the next two decades [3], [4], [5], [6]. A nexus between methamphetamine use and the development of heart failure was first recognized during this period [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. At present, methamphetamine use remains a significant problem that is expanding domestically and worldwide [20]. From the most recently published National Survey on Drug Use and Health (NSDUH) in 2015, approximately 897,000 people aged 12 or older were current users of methamphetamine, a substantial increase from 569,000 the prior year [21]. Visits to the emergency department have also increased significantly in the past decade [22]. According to the 2017 United Nations Drug Report, there are over 37 million estimated regular multinational methamphetamine users, with an annual prevalence of 0.77% [23]. Based on these statistics, it seems certain the prevalence of heart failure from methamphetamine use will increase in parallel, especially in younger patients with no other significant cardiac risk factors [24]. To address this issue, and to investigate the differences between methamphetamine users who develop heart failure versus those who do not, we extensively reviewed two years of clinical data. Another aim of our study was to determine if there were any predictive factors for the development of heart failure in patients using methamphetamine.

Section snippets

Methods

From August 1, 2014 to July 31, 2016, a retrospective review of all emergency department patients for whom BNP was tested was performed at an urban, academic Level I trauma center with an annual census of 80,000 visits. This facility serves a population of 500,000 within its city limits and 1.6 million in the surrounding area. The hospital serves as a tertiary referral center for Northern and Central California and is also the de facto public hospital providing care for a significant number of

Results

For the two-year study period, there were a total of 113,015 patients age greater than or equal to 18 years evaluated in the emergency department, and 4407 patients were positive for methamphetamine on their toxicology screen. Of these methamphetamine-positive patients, 714 were screened for heart failure with BNP testing (Table 1). The prevalence of abnormal BNP (> 100 pg/mL) in the methamphetamine-tested patient group was 10.2% (450/4407) versus 6.7% (7263/108,608) in the combined

Discussion

Our study demonstrated a high prevalence (10.2%) of heart failure in methamphetamine-positive patients with younger age and limited or no risk factors who were screened by BNP compared to methamphetamine-negative patients and those not tested (6.7%) presenting to the emergency department. The worldwide prevalence of heart failure among adults is approximately 1–2%, and > 10% among persons older than 70 years of age [26]. In the United States, the overall prevalence is 2.5% [27]. Heart failure is

Conclusion

Methamphetamine-positive patients have a significantly higher prevalence of heart failure than methamphetamine-negative patients or those not tested, and those who develop heart failure tend to be male, older, White, former smokers, and have higher creatinine, heart and respiratory rates. This subgroup also has greater biventricular dysfunction, dimensions, and higher pulmonary arterial pressures. The association of heart failure from methamphetamine use can be rationally explained from

Disclosure

The authors report no conflicts of interest.

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Cardiomyopathy-Associated Hospital Admissions Among Methamphetamine Users: Geographical and Social Disparities
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Methamphetamine is an emerging drug threat. The disparity in cardiomyopathy-associated hospital admissions among methamphetamine users (CAHMA) over the decade remains unknown.
The purpose of this study was to determine the trends and prevalence of CAHMA by age, sex, race, and geographical region.
We used data from 2008 to 2020 from the National Inpatient Sample database. We identified 12,845,919 cardiomyopathy-associated hospital admissions; among them, 222,727 were diagnosed as methamphetamine users. A generalized linear model with binomial link function was used to compute the prevalence ratio and 95% CI. Those who used other substances along with methamphetamine were excluded from the analysis.
CAHMA increased by 231% (P trend <0.001) from 2008 to 2020. CAHMA increased 345% for men (P trend <0.001) and 122% for women (P trend <0.001), 271% for non-Hispanic White (P trend <0.001), 254% for non-Hispanic Black (p trend <0.001), 565% for Hispanic (P trend <0.001), and 645% for non-Hispanic Asian (P trend <0.001) population. CAHMA also increased significantly in the West region (530%) (P trend <0.001) and South region (200%) (P trend <0.001) of the United States. Men, Hispanic population, age groups 26 to 40 and 41 to 64 years, and Western regions showed a significantly higher uptrend than their counterparts (P trend <0.001).
CAHMA have increased significantly in the United States. Men, Hispanics, non-Hispanic Asian, age groups 41 to 64. and western regions showed a higher proportional increase highlighting gender-based, racial/ethnic, and regional disparities over the study period.
Gut microbiota contribute to Methamphetamine-induced cardiotoxicity in mouse model
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Methamphetamine (METH) is a psychotropic drug known to cause cardiotoxicity. The gut-heart axis is emerging as an important pathway linking gut microbiota to cardiovascular disease, but the precise association between METH-induced cardiotoxicity and gut microbiota has yet to be elucidated. In this study, we established an escalating dose-multiple METH administration model in male BALB/c mice, examined cardiac injury and gut microbiota, and investigated the contribution of gut microbiota to cardiotoxicity induced by METH. Additionally, we treated mice with antibiotics and fecal microbiota transplantation (FMT) to assess the impact of gut microbiota on cardiotoxicity. Our results showed that METH exposure altered the p53 and PI3K/Akt signaling pathways and modulated the apoptosis pathway in heart tissue, accompanied by elevated levels of Bax/BCL-2 expression and cleaved caspase-3 proteins. METH exposure increased the diversity and richness of gut microbiota, and significantly changed the microbial community composition, accompanied by elevated abundance of Lactobacillus, Bifidobacterium, and decreased abundance of Bacteroides, norank_f_Muribaculaceae and Alistipes. Eliminating gut microbiota by antibiotics treatment alleviated METH-induced cardiotoxicity, while FMT treatment transferred similar cardiac injury manifestations from METH-exposed mice to healthy recipient mice. Our study unveils the crucial involvement of gut microbiota in the development of cardiotoxicity induced by METH and provides potential strategies for treating cardiac complications caused by METH.
Mitochondrial dysfunction and autophagy activation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats
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Citation Excerpt :
In our current study, our complementary gravimetric and histologic studies revealed increased heart weight and augmented cardiomyocytes cross-sectional areas in rat hearts subjected to 8-weeks of METH self-administration ‘binge and crash’ regime compared to age- and gender-matched control rats. A recent retrospective study identified abnormal brain natriuretic peptide (BNP) levels as a predictor of severe cardiac dysfunction (%LVEF <30%) in logistic regression analysis in METH HF patients [87]. Another retrospective study reported elevated BNP/pro-BNP levels corresponded to 90% documented HF in patients who use METH [79].
The recent rise in illicit use of methamphetamine (METH), a highly addictive psychostimulant, is a huge health care burden due to its central and peripheral toxic effects. Mounting clinical studies have noted that METH use in humans is associated with the development of cardiomyopathy; however, preclinical studies and animal models to dissect detailed molecular mechanisms of METH-associated cardiomyopathy development are scarce. The present study utilized a unique very long-access binge and crash procedure of METH self-administration to characterize the sequelae of pathological alterations that occur with METH-associated cardiomyopathy. Rats were allowed to intravenously self-administer METH for 96 h continuous weekly sessions over 8 weeks. Cardiac function, histochemistry, ultrastructure, and biochemical experiments were performed 24 h after the cessation of drug administration. Voluntary METH self-administration induced pathological cardiac remodeling as indicated by cardiomyocyte hypertrophy, myocyte disarray, interstitial and perivascular fibrosis accompanied by compromised cardiac systolic function. Ultrastructural examination and native gel electrophoresis revealed altered mitochondrial morphology and reduced mitochondrial oxidative phosphorylation (OXPHOS) supercomplexes (SCs) stability and assembly in METH exposed hearts. Redox-sensitive assays revealed significantly attenuated mitochondrial respiratory complex activities with a compensatory increase in pyruvate dehydrogenase (PDH) activity reminiscent of metabolic remodeling. Increased autophagy flux and increased mitochondrial antioxidant protein level was observed in METH exposed heart. Treatment with mitoTEMPO reduced the autophagy level indicating the involvement of mitochondrial dysfunction in the adaptive activation of autophagy in METH exposed hearts. Altogether, we have reported a novel METH-associated cardiomyopathy model using voluntary drug seeking behavior. Our studies indicated that METH self-administration profoundly affects mitochondrial ultrastructure, OXPHOS SCs assembly and redox activity accompanied by increased PDH activity that may underlie observed cardiac dysfunction.
New insight into methamphetamine-associated heart failure revealed by transcriptomic analyses: Circadian rhythm disorder
2022, Toxicology and Applied Pharmacology
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In the present study, blood pressure was not monitored during METH consumption, and the heart was not significantly enlarged after 4 weeks of METH consumption. The histopathological examination results in this study were in accordance with those of previous studies(Richards et al., 2018). However, the finding that METH induced the activation of fibroblasts and the transformation of fibroblasts to myofibroblasts contributed to the elevated secretion of Collagen I could provide new evidence for cardiac fibrosis in METH-related cardiotoxicity and reveal that the activation of fibroblasts played an important role in the development of cardiac fibrosis.
Methamphetamine (METH) abuse is a significant public health concern globally. Cardiac toxicity is one of the important characteristics of METH, in addition to its effects on the nervous system. However, to date, research on the cardiotoxic injury induced by METH consumption has been insufficient. To systematically analyze the potential molecular mechanism of cardiac toxicity in METH-associated heart failure (HF), a rat model was constructed with a dose of 10 mg/kg of METH consumption. Cardiac function was evaluated by echocardiography, and HE staining was used to clarify the myocardial histopathological changes. Integrated analyses, including mRNA, miRNA and lncRNA, was performed to analyze the RNA expression profile and the potential molecular mechanisms involved in METH-associated HF. The results showed that METH caused decreased myocardial contractility, with a decreased percent ejection fraction (%EF). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the RNAs with expression changes revealed abnormal circadian rhythm regulation in the METH groups, with circadian rhythm-related genes and their downstream effectors expressed differentially, especially the aryl hydrocarbon receptor nuclear translocator-like (Arntl). Competing endogenous RNA (ceRNA) networks associated with circadian rhythm, including Arntl, was also observed. Therefore, this study revealed that long-term METH consumption was associated with the HF in a rat model by decreasing the %EF, and that the abnormal circadian rhythm could provide new directions for investigating the METH-associated HF, and that the differentially expressed genes in this model could provide candidate genes for the identification and assessment of cardiac toxicity in METH-associated HF, which is fundamental for further understanding of the disease.
Methamphetamine-Associated Cardiomyopathy: Addressing the Clinical Challenges
2022, Heart Lung and Circulation
Citation Excerpt :
MA-CMP is an increasingly recognised disease entity in the midst of escalating community methamphetamine use [15]. Compared with other individuals with heart failure, observational studies have reported that patients with MA-CMP tend to be younger (50±10 vs 67±16 years) [8,29], predominantly male (60–93%) [15,19,29,30], and Caucasian [29]. Patients also tend to have fewer medical diagnoses, although more psychiatric comorbidities and social stressors [7,8], compared with patients with cardiomyopathy attributable to other causes [8,31,32].
The growth in methamphetamine usage worldwide continues to present increasing societal and health care challenges. With the escalation of its usage in a variety of social demographics, the entity of methamphetamine-associated cardiomyopathy (MA-CMP) has emerged. This entity is increasingly responsible for an important proportion of heart failure burden in both admissions to hospital and in those individuals requiring chronic heart failure care. MA-CMP poses some unique challenges including its recognition, particularly in younger patients presenting with new-onset heart failure, its severity at presentation and complications as well as management options. The challenging nature of methamphetamine addiction and the necessity to achieve abstinence is a fundamental aspect of management of this condition. As methamphetamine use continues at high levels in Australia, the burden of MA-CMP will inevitably increase and, therefore, all clinicians responsible for heart failure management require an awareness of this disease entity and the specific clinical challenges of its care.
Systolic dysfunction in patients with methamphetamine use and heart failure with preserved ejection fraction
2022, International Journal of Cardiology
Citation Excerpt :
These toxicities may lead to long term heart failure and pulmonary arterial hypertension (PAH) [2–6]. Methamphetamine associated heart failure (MethHF) is most commonly characterized by a non-ischemic, dilated cardiomyopathy with reduced ejection fraction [1–3,7–9]. We have previously shown that those with MU and heart failure with reduced ejection fraction have improvement in left ventricular ejection fraction (EF) with methamphetamine cessation [10].
Background: We aimed to evaluate for occult systolic dysfunction and the effect of methamphetamine cessation among patients with methamphetamine use (MU) and heart failure with preserved ejection fraction (HFpEF).
Methods: A retrospective cohort of patients with HFpEF with serial echocardiograms was stratified by MU and evaluated using myocardial strain analysis on echocardiograms at baseline and 1 year to measure global longitudinal strain (GLS). Contemporaneous controls with an ICD diagnosis of HF within 3 days of an MU case were chosen.
Results: Patients with MU (n = 31) were younger (49 ± 10 vs 59 ± 16 years, p < 0.01) and more frequently male (55% vs 26%, p = 0.04) than controls (n = 23). There was no baseline difference in ejection fraction (EF) (median 66% [IQR 58,71%] vs 62% [56,69%], p = 0.33) or GLS (−13.0% [−16.3,−10.9%] vs −14.8% [−16.0,−11.3%], p = 0.40). At one-year follow-up, MU cessation (n = 15) was associated with improvement in GLS (absolute change −4.4% [−6.5,−1.7%], p < 0.01), while no absolute change was observed with continued MU (n = 16) (0.74% [−1.2,2.8%], p = 0.22) or controls without MU (−0.6% [−2.1,2.8%], p = 0.78). Of those with abnormal baseline GLS, normalization was observed in 46% with MU cessation, none with continued MU, and 5% of controls (p < 0.001). Among MU patients, improvement in GLS was associated with decreased HF admissions per year [HR 0.74 per 1% change in GLS, 95% CI 0.55,0.98, p = 0.04].
Conclusions: Patients with MU and HFpEF may have occult systolic dysfunction as demonstrated by abnormal GLS, and MU cessation at 1 year is associated with improvement in GLS and a reduction in risk of HF admissions.

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Original ContributionMethamphetamine use and heart failure: Prevalence, risk factors, and predictors

Abstract

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Disclosure

J Emerg Med

Am Heart J

Forensic Sci Int

Am J Med

Drug Alcohol Depend

Hum Pathol

Chin Med Sci J

Pharmacol Ther

Brain Res Mol Brain Res

J Cardiovasc Magn Reson

Drug Alcohol Depend

Forensic Sci Int

J Am Coll Cardiol

Am J Med

Am J Cardiol

Heart Lung Circ

Heart Fail Clin

Amphetamine derivatives. In Cole S, ed. street drugs: new research. New York: Nova

Science

Methamphetamine. Stimulant of the 1990s?

West J Med

The prevalence of methamphetamine and amphetamine abuse in North America: a review of the indicators, 1992-2007

Drug Alcohol Rev

Methamphetamine use and emergency department utilization: 20 years later

J Addict

Amphetamine and methamphetamine emergency department visits

Propylhexedrine-induced left ventricular dysfunction

Ann Intern Med

Acute cardiomyopathy secondary to intravenous amphetamine abuse

Ann Intern Med

Acute amphetamine cardiomyopathy in a drug addict

Clin Cardiol

Amphetamine cardiomyopathy

Ann Intern Med

Reversible dilated cardiomyopathy induced by methamphetamine

Clin Cardiol

Cardiomyopathy associated with the smoking of crystal methamphetamine

JAMA

Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profiles

J Forensic Sci

Crystal methamphetamine-associated cardiomyopathy: tip of the iceberg?

J Toxicol Clin Toxicol

Sudden unexpected death of a methamphetamine abuser with cardiopulmonary abnormalities: a case report

Med Sci Law

Fatal amphetamine-associated cardiotoxicity and its medicolegal implications

Am J Forensic Med Pathol

Original Contribution
Methamphetamine use and heart failure: Prevalence, risk factors, and predictors