Abstract
Methamphetamine-associated cardiomyopathy continues to grow within the United States. Although initiation of guideline-directed medical therapy and cessation of methamphetamine are cornerstones of therapy, many barriers to guideline-directed medical therapy use exist for patients with methamphetamine-associated cardiomyopathy. This paper presents a case series of patients who demonstrated profound clinical and echocardiographic improvement with engagement in a community heart failure program paired with the use of alarmed pill containers to target medication adherence.
Key Words: alarmed pill container, heart failure, methamphetamine use
Visual Summary
Rates of methamphetamine-associated cardiomyopathy (MACM) and hospitalizations for associated heart failure (HF) are increasing exponentially in the United States.1,2 Methamphetamine affects the cardiovascular system through direct myocardial toxicity, accelerated atherosclerosis, and sympathetic stimulation.3 This manifests as acute myocarditis or chronic HF after prolonged use.4 Methamphetamine cessation is associated with improvement of MACM, but access to stimulant use disorder treatment is limited and there are no Food and Drug Administration-approved pharmacologic treatments; furthermore, not all patients have goals of stimulant abstinence.4, 5, 6 Clinically, patients with MACM with reduced left ventricular ejection fraction (LVEF) are started on guideline-directed medical therapy (GDMT) for HF, but there is limited data on clinical outcomes and LVEF recovery, particularly in those with continued stimulant use.7
Take-Home Messages
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Patients with MACM enrolled in the CHFP demonstrated improvement in LVEF after receipt of GDMT through an alarmed pill container.
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Our CHFP is a novel strategy to engage patients with MACM in care and up-titrate GDMT.
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Despite continued methamphetamine use, patients with MACM can have clinically meaningful improvement in LVEF and functional status with GDMT adherence.
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Alarmed pill containers provide a structured approach to help people with medication-adherence challenges and should be studied further.
Myriad obstacles to care exist for people with MACM, including mental health conditions, difficulty attending outpatient appointments, and medication adherence.8,9 Our institution developed the community heart failure program (CHFP), a mobile team of health care providers, to bring state-of-the-art cardiovascular care directly to patients. Patients enrolled in the CHFP are seen in the community, often a shelter or subsidized housing unit, by a team that includes a nurse, nurse practitioner, and physician. A visit may include a physical examination, blood work, medication management, patient education, and harm reduction strategies. Care delivery is centered around the patient and aligning with their goals. Although some patients demonstrated improved medications adherence with these outreach efforts, many continued to struggle. Accordingly, the CHFP began distributing alarmed pill containers to patients (Figure 1). These kits are locked until a set time each day, when they light up and audibly alarm until medications are taken. If the medications are not taken during that 30-minute window, the alarm stops, and the kit rotates to the next day to assess medication adherence.
Visual Summary.
LVEF Over Time for Patients With Methamphetamine-Associated Cardiomyopathy Engaged in the CHFP
CHFP = community heart failure program; LVEF = left ventricular ejection fraction.
Figure 1.
Alarmed Pill Containers Used by the Community Heart Failure Program
We present a case series of patients with MACM who demonstrated dramatic clinical and echocardiographic improvement after engagement with low-barrier clinical visits by the CHFP and use of alarmed pill containers, despite continued methamphetamine use (Table 1).
Table 1.
Each Patient’s Left Ventricular Ejection Fraction at CHFP Intake, Initiation of the Alarmed Pill Box Strategy, and Most Recent Echocardiogram
| CHFP Initial Visit, % | Alarm Pill Box, % | Contemporaneous, % | |
|---|---|---|---|
| Patient 1 | 16 | 22 | 49 |
| Patient 2 | 20 | --- | 42 |
| Patient 3 | 33 | --- | 60 |
CHFP = community heart failure program.
Case 1
A 52-year-old man with housing instability and a 30-year-history of methamphetamine, fentanyl, and heroin use presented to the emergency department with progressive exertional dyspnea and lower extremity edema. A transthoracic echocardiogram demonstrated a severely dilated left ventricle (left ventricular end diameter volume indexed 161 mL/m2) with severely reduced systolic function (LVEF 16%), severely dilated right ventricle with moderately reduced function, and elevated pulmonary artery systolic pressure, at 62 mm Hg (Videos 1 and 2). He was diagnosed with MACM after invasive coronary angiogram and serologic nonischemic work-up was unrevealing. He was initiated on GDMT (lisinopril 10 mg and metoprolol succinate 25 mg daily) with a loop diuretic and was discharged with outpatient cardiology follow-up. He experienced challenges with medication adherence and clinic attendance, resulting in recurrent hospitalizations for decompensated HF. Because his LVEF remained depressed (16%-32%), he was referred to the CHFP. Despite CHFP engagement, he struggled with medication adherence, and was provided an alarmed pill container.
Subsequently, the patient reported significant improvement in symptoms, with NYHA functional class I symptoms and 100% medication adherence to lisinopril 5 mg, metoprolol succinate 12.5 mg, eplerenone 25 mg, and empagliflozin 10 mg daily. His LVEF improved from 16% to 49%. His left ventricle size decreased (left ventricular end diameter volume indexed 111 mL/m2), and pulmonary artery systolic pressure normalized to 26 mm Hg (Videos 3 and 4). Importantly, these improvements with outreach engagement and medication adherence occurred despite continued fentanyl and methamphetamine use.
Case 2
A 71-year-old man with mixed cardiomyopathy due to cocaine and methamphetamine use and obstructive coronary artery disease (95% stenosis of mid left anterior descending artery status post drug-eluting stent) was admitted with decompensated HF. His LVEF was 20% (previously 35%) and he reported NYHA functional class IV symptoms. With negative cardiac biomarkers and an electrocardiogram negative for ischemic changes, progressive coronary artery disease was deemed unlikely to cause his LVEF deterioration. He was previously prescribed losartan, metoprolol succinate, spironolactone, and empagliflozin, but struggled with adherence given vision and memory impairments. After discharge, he received an alarmed pill container. His medication adherence subsequently approached 100%.
On last visit with the CHFP, he reported NYHA functional class I symptoms, and recognized the association between medication adherence and symptomatic improvement. Despite continued stimulant use, LVEF improved from 20% to 42% over the following year. His cardiac recovery was complicated by multiple unintentional opioid overdoses from fentanyl contamination. CHFP providers prescribed naltrexone, and the patient has not had any further opioid overdoses.
Case 3
A 61-year-old man with opioid use disorder on buprenorphine-naloxone, active methamphetamine use, and MACM (LVEF 33%) was referred to the CHFP due to challenges with medication adherence and outpatient follow-up. He was unable to engage in outpatient care and had more than 10 hospitalizations each year.
On CHFP intake, he reported NYHA functional class III symptoms and was only prescribed a diuretic that he took inconsistently. With an alarmed pill container, his medication adherence drastically improved. Over the next 4 months the CHFP optimized his GDMT, adding losartan 25 mg, metoprolol succinate 25 mg, spironolactone 25 mg, and empagliflozin 10 mg daily.
At his most recent visit with the CHFP, the patient reported NYHA functional class I symptoms, with decreased methamphetamine use. Transthoracic echocardiogram showed LVEF recovery from 33% to 60%.
Discussion
These 3 cases represent a larger cohort of patients with MACM in our health system who derived significant benefit from engagement with the CHFP, a novel HF outreach model of care that overcomes barriers to care for people with MACM. This case series is the first description of a community-based outreach model to provide equitable care for people with MACM. Engagement in the CHFP allowed for regular follow-up, rapid GDMT up-titration, and improved medication adherence, which is remarkable given challenges engaging this population in care due to mistrust and barriers to care.
GDMT is the cornerstone for HF with reduced ejection fraction, but there are limited data on GDMT in MACM. Multiple studies highlight how methamphetamine cessation can lead to improvement in LVEF and functional status.4,5 However, with the challenges of treating methamphetamine use disorder, studying MACM outcomes among patients with continued methamphetamine use is imperative.10 Patients in this case series demonstrated remarkable HF improvement and adherence to GDMT despite ongoing stimulant use.
Successful adherence to GDMT was accomplished using alarmed pill containers, a novel approach among patients with MACM. While initially studied in patients with dementia and Parkinson disease, Hale et al11 found alarmed pillboxes with remote monitoring in HF reduced all-cause hospitalizations. Our findings were similar, with patients in our series experiencing robust improvement in symptoms, LVEF, and medication adherence temporally correlated with initiation of alarmed pill container use. Notably, patients in this case series were not treated with an angiotensin receptor/neprilysin inhibitor because alarmed pill containers only allowed for once-daily medications. Given the exciting findings reported in our case series, the utility of alarmed pill containers for HF should be studied more rigorously among patients with MACM and other populations.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
4-Chamber View of the Heart of Patient 1 Prior to Community Heart Failure Program Engagement
2-Chamber View of the Heart of Patient 1 Prior to Community Heart Failure Program Engagement
4-Chamber View of the Heart of Patient 1 After Community Heart Failure Program Engagement
2-Chamber View of the Heart of Patient 1 After Community Heart Failure Program Engagement
References
- 1.Dickson S.D., Thomas I.C., Bhatia H.S., et al. Methamphetamine-associated heart failure hospitalizations across the United States: geographic and social disparities. J Am Heart Assoc Cardiovasc Cerebrovasc Dis. 2021;10(16) doi: 10.1161/JAHA.120.018370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Al -Yafeai Zaki, Ali S., Brown J., et al. Cardiomyopathy-associated hospital admissions among methamphetamine users: geographical and social disparities. JACC Adv. 2024;3(7) doi: 10.1016/j.jacadv.2024.100840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Reddy P.K.V., Ng T.M.H., Oh E.E., Moady G., Elkayam U. Clinical characteristics and management of methamphetamine-associated cardiomyopathy: state-of-the-art review. J Am Heart Assoc. 2020;9(11) doi: 10.1161/JAHA.120.016704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Schürer S., Klingel K., Sandri M., et al. Clinical characteristics, histopathological features, and clinical outcome of methamphetamine-associated cardiomyopathy. JACC Heart Fail. 2017;5(6):435–445. doi: 10.1016/j.jchf.2017.02.017. [DOI] [PubMed] [Google Scholar]
- 5.Voskoboinik A., Ihle J.F., Bloom J.E., Kaye D.M. Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery. Intern Med J. 2016;46(6):723–727. doi: 10.1111/imj.13050. [DOI] [PubMed] [Google Scholar]
- 6.Zhao S.X., Seng S., Deluna A., Yu E.C., Crawford M.H. Comparison of clinical characteristics and outcomes of patients with reversible versus persistent methamphetamine-associated cardiomyopathy. Am J Cardiol. 2020;125(1):127–134. doi: 10.1016/j.amjcard.2019.09.030. [DOI] [PubMed] [Google Scholar]
- 7.Bhatia H.S., Nishimura M., Dickson S., Adler E., Greenberg B., Thomas I.C. Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation. Heart Br Card Soc. 2021;107(9):741–747. doi: 10.1136/heartjnl-2020-317635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Manja V., Nrusimha A., Gao Y., et al. Methamphetamine-associated heart failure: a systematic review of observational studies. Heart. 2023;109(3):168–177. doi: 10.1136/heartjnl-2022-321610. [DOI] [PubMed] [Google Scholar]
- 9.Manja V., Sandhu A.T.S., Asch S., et al. Healthcare utilization and left ventricular ejection fraction distribution in methamphetamine use associated heart failure hospitalizations. Am Heart J. 2024;270:156–160. doi: 10.1016/j.ahj.2023.12.014. [DOI] [PubMed] [Google Scholar]
- 10.Hersi M., Corace K., Hamel C., et al. Psychosocial and pharmacologic interventions for problematic methamphetamine use: findings from a scoping review of the literature. PLoS One. 2023;18(10) doi: 10.1371/journal.pone.0292745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hale T.M., Jethwani K., Kandola M.S., Saldana F., Kvedar J.C. A remote medication monitoring system for chronic heart failure patients to reduce readmissions: a two-arm randomized pilot study. J Med Internet Res. 2016;18(4) doi: 10.2196/jmir.5256. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
4-Chamber View of the Heart of Patient 1 Prior to Community Heart Failure Program Engagement
2-Chamber View of the Heart of Patient 1 Prior to Community Heart Failure Program Engagement
4-Chamber View of the Heart of Patient 1 After Community Heart Failure Program Engagement
2-Chamber View of the Heart of Patient 1 After Community Heart Failure Program Engagement