neeki2016

Frequency of Methamphetamine Use as a Major
Contributor Toward the Severity of Cardiomyopathy
in Adults £50 Years
Michael M. Neeki, DO, MSa, Michael Kulczycki, DOa, Jake Toy, BAb, Fanglong Dong, PhDb,
Carol Lee, MDa, Rodney Borger, MDa, and Sasikanth Adigopula, MDc,*
Methamphetamine is one of the most commonly abused illegal drugs in the United States.
Health care providers are commonly faced with medical illness caused by methamphetamine. This study investigates the impact of methamphetamine use on the severity of
cardiomyopathy and heart failure in young adults. This retrospective study analyzed
patients seen at Arrowhead Regional Medical Center from 2008 to 2012. Patients were
between 18 and 50 years old. All patients had a discharge diagnosis of cardiomyopathy or
heart failure. The severity of disease was quantified by left ventricular systolic dysfunction:
heart failure with preserved ejection fraction to mildly reduced if ejection fraction
was >40% and moderate to severely depressed if ejection fraction was £40%. Methamphetamine abuse was determined by a positive urine drug screen or per documented
history. Of the 590 patients, 223 (37.8%) had a history of methamphetamine use. More than
half the population was men (n [ 389, 62.3%); 41% was Hispanic (n [ 243), 25.8% was
Caucasian (n [ 152), and 27.8% was African-American (n [ 164); 60.9% were in the age
range of 41 to 50 years (n [ 359). Patients with a history of methamphetamine use had
increased odds (odds ratio [ 1.80, 95% confidence interval 1.27 to 2.57) of having a
moderately or severely reduced ejection fraction. Additionally, men were more likely
(odds ratio 3.13, 95% confidence interval 2.14 to 4.56) to have worse left ventricular
systolic dysfunction. In conclusion, methamphetamine use was associated with an
increased severity of cardiomyopathy in young adults. Ó 2016 Elsevier Inc. All rights
reserved. (Am J Cardiol 2016;118:585e589)
Although there are extensive published reports on the
cardiovascular pathophysiology, psychological effects, and
behavioral effects of methamphetamine use, there is limited
evidence pertaining to the development of early heart
failure among users.1,2 We investigate the association of
methamphetamine use and a diagnosis of cardiomyopathy
or heart failure in adults 50 years. To our knowledge, this
is the largest clinical study investigating this association.
A previous study described this association in native
Hawaiian and Pacific Islander populations and showed
methamphetamine use to be an independent risk factor
for cardiomyopathy or heart failure. The ethnic
demographics for that study population was largely limited
by geography.3
This study includes a large sample size and a diverse
demographic in an urban tertiary care center located in San
Bernardino County, California.
a
Department of Emergency Medicine, Arrowhead Regional Medical
Center, Colton, California; bWestern University of Health Sciences, College
of Osteopathic Medicine of the Pacific, Pomona, California; and cDepartment of Cardiology, Advanced Heart Failure and Heart Transplantation,
Loma Linda University Medical Center, Loma Linda, California. Manuscript received March 7, 2016; revised manuscript received May 7, 2016;
accepted May 23, 2016.
See page 588 for disclosure information.
*Corresponding author: Tel: 7087900512; fax: 9095580309.
E-mail address: [email protected] (S. Adigopula).
0002-9149/16/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjcard.2016.05.057
Methods
This study was approved by the Institutional Review
Board at the Arrowhead Regional Medical Center (ARMC)
and was a retrospective chart review study. ARMC is a
456-bed acute care teaching facility and one of the 2
American College of Surgeonsecertified level II trauma
centers located in San Bernardino County, California.4 San
Bernardino County is the largest county in the contiguous
United States and has an estimated population of 2,091,618
in 2014. The predominant ethnicity is Latino at 51%.
Among non-Latino residents, 31% are white, 8% are
African-American, 7% are Asian or Pacific Islander, and
3% reported as 2 races or American Indian/Alaska Native
or other.5
Emergency department patients seen at ARMC from
January 2008 to December 2012 were analyzed for inclusion in this study. Patients were selected from both genders
and all ethnicities. Patients were included if they were 18 to
50 years old and had a discharge diagnosis of cardiomyopathy or heart failure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to select
patients with a diagnosis of cardiomyopathy (ICD-9: 425.2
to 425.9) or heart failure (ICD-9: 428.0 to 428.9). Methamphetamine use was determined by a positive urine drug
screen or by documentation in the patient’s chart by the
physician. Patients with a history of coronary artery disease
or valvular heart disease were excluded from the multivariate logistic regression. Among women, patients who were
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Table 1
Patient demographic information
Variable
Female
Male
Black
Hispanic
Other
White
Age (years)
18-30
31-40
41-50
Methamphetamine Use
Tobacco Use
Alcohol Use
Cocaine Use
Marijuana Use
Diabetes Mellitus
Hypertension
Dyslipidemia
Ejection Fraction
>40%
40%
Figure 1. A retrospective extensive chart review was performed, and 862
patients with a history of cardiomyopathy were identified. Patients who
did not have documented EF and patients who had other reasons to have
cardiomyopathy (coronary artery disease, valvular heart disease, and peripartum cardiomyopathy) were excluded.
suspected to have peripartum cardiomyopathy were
excluded regardless of methamphetamine use. For patients
with multiple admissions, only data from the initial visit
were recorded and repeat hospitalizations were excluded.
The primary outcome was the severity of LV systolic
dysfunction as characterized by ejection fraction (EF)
reduction. For study purposes, EF reduction severity, as
determined by an echocardiogram, was categorized as
follows: heart failure with preserved ejection fraction
(HFpEF) to mildly reduced EF >40% and moderately to
severely reduced EF 40%. Selection of 40% as a baseline for clinically significant LV systolic dysfunction was
based on its predictive value of cardiovascular outcome and
indication for specific treatment protocols.6e11
Analyzed predictors included age, ethnicity, methamphetamine use, tobacco use, alcohol use, cocaine use,
marijuana use, diabetes, hypertension, and dyslipidemia.
Ethnicity was further categorized into 4 groups: Hispanic,
Caucasian, African-American, and other. Substance use
Frequency (N¼590)
Percent
228
362
164
242
32
152
(39%)
(61%)
(28%)
(41%)
(5%)
(26%)
57
174
359
223
313
254
50
98
216
452
255
(10%)
(30%)
(61%)
(38%)
(53%)
(43%)
(9%)
(17%)
(37%)
(77%)
(43%)
367
223
(62%)
(38%)
history and the presence of diabetes, hypertension, and
dyslipidemia were obtained through chart review.
All data were analyzed using the SAS software for
Windows, version 9.3 (Cary, North Carolina). Descriptive
statistics were presented as frequencies and proportions for
categorical variables. A chi-square crosstab analysis was
conducted to assess the association between predictors and
severity of EF reduction (mild vs moderate to severe). A
logistic regression was conducted using PROC LOGISTIC
to identify factors associated with the severity of EF
reduction (mildly vs moderately to severely reduced EF).
The possible predictor included in the logistic regression
included all the significant variables identified by the
crosstab analysis. All statistical analyses were 2 sided;
p value <0.05 was considered statistically significant.
Results
A total of 862 patients with a discharge diagnosis of
cardiomyopathy or heart failure were identified and assessed
for inclusion in the study. Patients who lacked a noted EF in
their chart (n ¼ 238), who had a history of peripartum
cardiomyopathy (n ¼ 4), and who had a history of CAD or
valvular heart disease (n ¼ 30) were excluded; 590 patients
were included in the final analysis (Figure 1 for patients flow
chart). The demographic information is presented in
Table 1. More than half the population were men (61%);
they were Hispanic (41%), Caucasian (26%), or AfricanAmerican (27%) and within the age range of 41 to 50 (61%).
Of the 590 patients, 223 had associated methamphetamine use, which represented 38% of our study population.
There was a significant correlation between the prevalence
of methamphetamine use and ethnicity (Table 2). Patients
aged 41 to 50 years were the most likely to use methamphetamine. Men were more likely than women to use
Cardiomyopathy/Methamphetamine Use and Cardiomyopathy Severity
Table 2
Crosstab analysis of methamphetamine use by demographic variables
within the study population*
Variable
Methamphetamine Use
No (n¼367)
Table 3
Crosstab analysis of factors associated with levels of ejection fraction
Variable
P-value
Left Ventricular Ejection Fraction
>40% (n¼367)
40% (n¼223)
Female
Male
177 (78%)
190 (53%)
51 (22%)
172 (48%)
Black
Hispanic
Other
White
Age (years)
18-30
31-40
41-50
Methamphetamine Use
Tobacco Use
Alcohol Use
Cocaine Use
Marijuana Use
Diabetes Mellitus
Hypertension
Dyslipidemia
98
155
19
95
(60%)
(64%)
(59%)
(63%)
66
87
13
57
(40%)
(36%)
(41%)
(38%)
30
110
227
119
177
151
31
58
131
285
163
(53%)
(63%)
(63%)
(53%)
(57%)
(60%)
(62%)
(59%)
(61%)
(63%)
(64%)
27
64
132
104
136
103
19
40
85
167
92
(47%)
(37%)
(37%)
(47%)
(44%)
(41%)
(38%)
(41%)
(39%)
(37%)
(36%)
Yes (n¼223)
Age (years)
18-30
31-40
41-50
38 (67%)
119 (68%)
210 (59%)
19 (33%)
55 (32%)
149 (42%)
Female
Male
148 (65%)
219 (61%)
80 (35%)
143 (40%)
Black
Hispanic
Other
White
128
153
27
59
0.8295
0.2815
<.0001
36
89
5
93
P-value
<.0001
0.0667
(78%)
(63%)
(84%)
(39%)
587
(22%)
(37%)
(16%)
(61%)
* The total row percentage may not add up to 100% due to rounding.
methamphetamine. More than half (61%) of the Caucasians
in the study population were methamphetamine users, followed by Hispanics and African-Americans.
Table 3 presents the analysis of various factors associated
with the severity of cardiomyopathy among these patients.
Patients with a history of methamphetamine use were at a
greater risk of having a moderate to severely reduced EF
(47% vs 32%, p ¼ 0.0006). Additionally, men were more
likely to have moderate to severely reduced EF compared
with women (48% vs 22%, p <0.0001). Tobacco users in
comparison with non-tobacco users had a moderate to
severely reduced EF (44% vs 31%, p ¼ 0.0026). Other
factors, including ethnicity, age, alcohol use, cocaine use,
marijuana use, diabetes, hypertension, and dyslipidemia,
were not statistically significantly associated with EF
severity among the cardiomyopathy patients.
Methamphetamine use, gender, and tobacco use were
further analyzed for the association with the severity of
cardiomyopathy from a multivariable logistic analysis
perspective. The results are presented in Table 4.
Compared with patients without a history of methamphetamine use, patients with a history of methamphetamine use
were more likely to experience moderate to severely
reduced EF (adjusted odds ratio ¼ 1.80, 95% confidence
interval 1.27 to 2.57). Moreover, men showed a greater risk
than women to experience moderate to severely reduced EF
(adjusted odds ratio ¼ 3.13, 95% confidence interval 2.14
to 4.56). Tobacco use was significantly associated with
the severity of cardiomyopathy at the univariate level
but no longer when adjusted for methamphetamine use
and gender.
Discussion
The present study showed that 38% of patients with
cardiomyopathy had associated methamphetamine use.
These patients with a history of methamphetamine use
were at a greater risk for a more severe form of cardiomyopathy or heart failure in comparison with nonusers.
Furthermore, our findings show that methamphetamine use
was an independent risk factor for an increase in the
0.2925
0.0006
0.0026
0.2302
0.9753
0.4996
0.5538
0.4411
0.4527
Table 4
Prediction of moderately or severely reduced ejection fraction using logistic
regression*
Variable
Methamphetamine Use
(yes vs no)
Male vs female
Tobacco Use (yes vs no)
Unadjusted
Odds Ratio
Adjusted Odds
Ratio
1.82 (1.29, 2.56)
1.80 (1.27, 2.57)
3.14 (2.16, 4.57)
0.59 (0.43, 0.84)
3.13 (2.14, 4.56)
* Predictor included in the ordinal logistic regression include: Methamphetamine Use (yes vs no), gender (male vs female), and Tobacco use
(yes vs no). Only gender and methamphetamine use were significant
predictors for the adjusted odds ratio estimate.
severity of cardiomyopathy and heart failure. To our
knowledge, this is the first cohort study addressing this
association in the contiguous United States. Our findings
build on an increasing pool of evidence elucidating
the correlation between methamphetamine use and a
diagnosis of cardiomyopathy or heart failure in adult
patients 50 years. Our study also established that this
relation exists across multiple ethnic groups and
geographical regions.3
Additionally, the results of our study demonstrated that
men were more likely to develop a severe form of cardiomyopathy than women. The difference is likely because of
an increased prevalence of methamphetamine use in men
within the study population.
In this study, patients with cardiomyopathy did not have
a positive association with cocaine use. The low prevalence
of cocaine use in our study population (8%) could have been
a contributing factor. This finding was also noted in a
previous study analyzing cardiomyopathy and methamphetamine use.3
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The American Journal of Cardiology (www.ajconline.org)
In adults 50 years with heart failure, methamphetamine
associated cardiomyopathy is increasing in prevalence in the
United States and requires a team-based approach for
effective management. This would include cardiologists,
primary care physicians, emergency physicians, mid-level
practitioners, psychiatrists, social workers, and drug
addiction specialists working together to control this rising
epidemic.
From previous studies, it is recognized that the cardiomyopathy associated with methamphetamine use appears to
be potentially reversible on cessation of methamphetamine.2,12e16 However, the exact window of
reversibility, the degree of reversibility, and the incidence of
reversibility are unclear. A previous study demonstrates that
patients with methamphetamine-associated severe cardiomyopathy can make a full recovery after discontinuation of
methamphetamine with no lasting fibrosis as determined
through cardiovascular magnetic resonance.17 Removal of a
pheochromocytoma to reverse severe cardiac dysfunction
has been well described.18e21 It appears that improvement
of cardiac function, after the discontinuation of methamphetamine, may act through a similar mechanism with the
return of catecholamine levels to normal. The plausibility
that methamphetamine-associated cardiomyopathy can be
reversed has serious medical and social implications. Early
detection is extremely important.
The selection of an EF 40% as a baseline for clinically
significant left ventricular systolic dysfunction was based on
current guidelines.6 Although it is recognized that
methamphetamine-associated cardiomyopathy predominantly presents as heart failure with reduced EF with an EF
40%, its likelihood to present as HFpEF or as mild LV
systolic dysfunction has not been well studied. The likelihood of hospitalization and risk of death due to heart failure
is strongly correlated with an EF 40%.9 Because methamphetamine use is correlated with severe cardiomyopathy,
users are at an increased risk for adverse medical outcomes
and for need of expensive drug and device therapy.
Selection of patients between the ages of 18 and 50 was
based on data demonstrating a decreased prevalence of agerelated ischemic cardiomyopathy in this demographic.22
Inclusion of all age groups would have increased the
applicability of our findings to the general population.
However, inclusion of subjects >50 years could have presented as a confounding factor in determining if methamphetamine was an independently associated risk factor for
worsened cardiomyopathy. A significantly larger sample
size would be required to identify this.
There were a number of limitations in our study. We
were only to able collect data from hospitalized patients
with cardiomyopathy at a single tertiary care center.
Nonhospitalized patients with mild or subclinical cardiomyopathy could not be included. As a result, our study
population represents only a subset of patients with a
diagnosis of cardiomyopathy and associated methamphetamine use, particularly those with a severe form of cardiomyopathy. The primary diagnostic measure was limited to
echocardiogram as many patients seen in the emergency
department at ARMC do not undergo further workups. We
were also unable to assess the duration of methamphetamine
use as a risk factor for developing cardiomyopathy as data
were only collected from the initial hospital visit. However,
positive urine toxicology was complemented by physician
documentation of a history of chronic methamphetamine
use.
A second limitation was the categorization of the severity
of a patient’s cardiomyopathy solely through EF. This does
not allow us to quantify the severity of heart failure in those
patients with HFpEF. However, previous studies indicate
that methamphetamine-associated cardiomyopathy often
presents as dilated cardiomyopathy with a reduced EF.2,16
Additional studies are warranted to elucidate the exact
clinical
manifestations
and
pathophysiology
of
methamphetamine-induced HFpEF.
Another limitation is the possibility that methamphetamine users may be less compliant with medications and
dietary recommendations, thus increasing their risk of
severe cardiomyopathy. However, nonadherence to medications has varied widely among many studies in heart
failure. Our study highlights cardiomyopathy and heart
failure that is likely related to methamphetamine use.
A final limitation was that data for this study were
gathered through a retrospective review of hospital records
at a single tertiary care center increasing the likelihood for
selection bias. Toxicology screening is not routinely
performed on all patients. It is also possible that some
practitioners did not investigate substance abuse history in
detail, particularly with respect to methamphetamine.
Patients may also be hesitant to disclose a history of
methamphetamine use. These factors have the potential to
alter the prevalence of methamphetamine use and association of the demographic variables in the study population.
Acknowledgment: The authors would like to acknowledge
Jonathan Lee, RN, MSN, and Massoud Rabiei, BS, for
assisting with the initial data collection and database
compilation.
Disclosures
The authors have no conflicts of interest to disclose.
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