By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports no financial relationships relevant to this field of study.

SYNOPSIS: In a large study of methamphetamine users, female sex was associated with presence of pulmonary hypertension, whereas male sex, hypertension, and alcoholism were associated with cardiomyopathy. Both pulmonary hypertension and cardiomyopathy patients exhibited substantially increased mortality.

SOURCE: Zhao SX, Kwong C, Swaminathan A, et al. Clinical characteristics and outcome of methamphetamine-associated pulmonary arterial hypertension and dilated cardiomyopathy. JACC Heart Fail 2018;6:209-218.

Methamphetamine (MA) use has been associated with both cardiomyopathy (CMP) and pulmonary arterial hypertension (PAH). However, both conditions remain under-studied and little is known about the similarities and differences between these conditions regarding risk factors, morbidity, and mortality.

Zhao et al retrospectively identified all patients with either a MA-related diagnosis or positive toxicology screen at a large public hospital in Northern California between 2010 and 2017. MA-PAH was defined as an estimated right ventricular systolic pressure > 45 mmHg by transthoracic echocardiography (TTE) in the absence of an alternative cause for pulmonary hypertension. MA-CMP was defined as a left ventricular ejection fraction (LVEF) persistently < 40% without an alternative explanation such as valvular or coronary artery disease. The control group consisted of patients who reported MA use but showed no evidence of cardiovascular disease on TTE. Of 4,662 MA users identified during the study period, 296 were included in the MA-CMP group, 50 in the MA-PAH group, and 356 in the control group. Patients with MA-PAH were more likely to be female (58%), and when compared to the control group, sex was the only significant predictor of MA-PAH (odds ratio [OR] for male sex, 0.49; P = 0.023). The MA-CMP group was predominantly male (86%). In a multivariate regression analysis, male sex (OR, 3.8; P < 0.001), alcohol abuse (OR, 3.0; P < 0.001), and hypertension (OR, 2.1; P < 0.001) all were strongly associated with MA-CMP compared to controls.

Among MA-CMP patients, median EF was 25.2 ± 6.5%, with biventricular dilation in many patients, and 57% demonstrated New York Heart Association functional class III or IV symptoms. The MA-PAH group also exhibited evidence of advanced disease. In those who underwent right heart catheterization, the median pulmonary vascular resistance was 11.8 Wood units (interquartile range, 9.0-15.3). Most patients demonstrated reduced cardiac index and elevated right atrial pressure.

Over a median follow-up of 20 months, both MA-CMP and MA-PAH were associated with increased mortality (18.0% and 15.2%, respectively, compared to 4.5% mortality in the control group; P < 0.001 for the overall comparison). There was no statistically significant difference in survival between the MA-CMP and MA-PAH groups (P = 0.697).

The authors concluded that MA-CMP and MA-PAH carry distinct risk factors, with female sex associated with MA-PAH, whereas male sex, hypertension, and alcoholism are associated with MA-CMP. Both conditions are associated with increased mortality.

COMMENTARY

MA use is increasing across the United States. The association between MA abuse and cardiovascular disease is widely recognized, although the exact pathophysiology is not understood completely. Increased catecholamine levels, with resulting hypertension, tachycardia, and vasoconstriction, contribute to the development of cardiomyopathy, and direct cell injury may play a significant role, too. Both cardiomyopathy and PAH are recognized complications of long-term MA use, although most current literature about these conditions is limited to case series with small sample sizes. In the largest published cohort of MA-related cardiovascular disease, Zhao et el clearly showed MA-CMP and MA-PAH are two distinct diseases, with different risk factors and patient profiles. However, both conditions are associated with substantial morbidity and increased mortality.

In both MA-CMP and MA-PAH, the disease severity was remarkable. The median EF of 25% in CMP, with most patients reporting functional class III or IV symptoms, as well as the marked hemodynamic and echocardiographic abnormalities in the MA-PAH group, speak to the profoundly detrimental effects of MA on the cardiovascular system. It also likely reflects delays in seeking care and medication nonadherence, two of the many factors that make MA users a particularly challenging population to treat.

This was a retrospective study with the usual limitations, including confounding. The authors could not address the important question of how the disease trajectory and outcomes are influenced by whether a patient can quit using MA. Despite these basic limitations, this study represents a crucial step toward better understanding of the risk factors, patient characteristics, and outcomes associated with the two main cardiovascular complications of chronic MA abuse.

No therapy has specifically been shown to improve outcomes in MA-CMP or MA-PAH, but providers should use standard guideline-based therapies for chronic heart failure and pulmonary hypertension as appropriate. Probably the most important lesson is that everyone who treats cardiovascular disease needs at least basic familiarity with MA and to keep it in mind during the workup of PAH or cardiomyopathy.

As a cardiologist in a region with particularly high rates of MA use, I ask about MA use and order toxicology screens in nearly all new patients with PAH or nonischemic cardiomyopathy routinely. Many patients are unaware of the link between MA use and their declining health, and explaining the association as well as the high mortality associated with these conditions can be very helpful for motivating patients to quit.