A new study sheds light on two poorly understood cardiac complications of methamphetamine (MA) abuse: pulmonary arterial hypertension (PAH) and dilated cardiomyopathy (CMP).
In what is believed to be the largest case series to date, investigators found that the clinical features of patients with MA-PAH and MA-CMP are distinct from each other, but both carry significant disease burden and mortality risk.
There is also a “striking sex imbalance between these two pathologies,” Susan X Zhao, MD, Santa Clara Valley Medical Center, San Jose, California, told theheart.org | Medscape Cardiology.
“Methamphetamine abuse is like a silent tsunami, sweeping upwards of 33 million people worldwide along its deadly path,” said Zhao. “Unlike opioid abuse, which can lead to overdose-related death, the detrimental effects of methamphetamine are more long-term and less well known.”
Their results are published in the March issue of JACC: Heart Failure.
MA abuse exerts its cardiotoxic effects by stimulating release of catecholaminergic neurotransmitters in both the central and peripheral nervous system, which modulates heart rate and blood pressure. MA abuse is known to cause PAH and CMP, but until now no study has compared the clinical characteristics and overall impact on survival of these two distinct pathologies.
“Silent Tsunami”
Zhao and colleagues retrospectively studied the clinical characteristics and outcomes of 50 patients with MA-PAH, 296 with MA-CMP, and 356 control patients with a documented history of MA abuse but without overt cardiac pathology (MA-CTL).
They found a strong female predominance in the MA-PAH group (58%) and a strong male predominance in the MA-CMP group (86%). Alcoholism and hypertension were more common in the MA-CMP group.
Both the MA-CMP and the MA-PAH groups had advanced disease with significant morbidity and mortality. The mean left ventricular ejection fraction in the MA-CMP group was 25.2% with dilated left and right ventricles, whereas the MA-PAH group had a median right ventricular (RV) systolic pressure of 75 mm Hg with dilated right heart and significantly reduced RV systolic function.
More than half (57%) of patients with MA-CMP had New York Heart Association functional class III/IV heart failure during follow-up, but only 14% of them received an implantable cardioverter-defibrillator to prevent sudden arrhythmic death. This is likely due to a combination of reasons, including ongoing substance abuse, poor functional status/prognosis, and/or issues with adherence, the researchers say.
After a median follow-up of 20 months, both MA-CMP and MA-PAH were associated with significantly increased mortality (18.0% and 15.2%, respectively), above and beyond that seen in the MA-CTL group (4.5%).
On logistic regression analyses, male sex, concurrent alcohol abuse, and the presence of systemic hypertension were independent factors associated with MA-CMP. The combination of MA and alcohol increases heart rate and blood pressure beyond those seen in MA users alone. This pharmacologic interaction may explain the significantly higher prevalence of systemic hypertension in the MA-CMP group, the investigators say.
In contrast with MA-CMP, the only clinical factor shown to be associated with MA-PAH was female sex. Women made up 58% of the MA-PAH group, compared with 14% of the MA-CMP group.
These results, say the researchers, suggest that the scale is tipped toward the MA-CMP phenotype when the MA user is male, with concomitant alcohol abuse and presence of systemic hypertension, whereas female sex and some other unknown factors, which may be clinical and/or genetic, predispose to the development of MA-PAH.
Limitations of the study include its retrospective design, as well as incomplete information on the duration and route of MA administration, which may play a key role in determining susceptibility in a given patient to a particular cardiovascular complication subtype.
Going forward, the investigators say future research is needed to establish a mechanistic relationship between MA use and these distinct forms of cardiac pathology, as well as the interaction of MA with other concurrent risk factors (such as alcohol abuse) or pre-existing cardiac conditions (such as hypertension).
The authors of an accompanying editorial say this study focuses “much-needed attention on the importance of MA in cardiovascular disease. Unfortunately, there are currently no approved pharmacologic therapies for MA and relapse rates after cognitive therapy as high as 88% have been documented,” note Ori Ben-Yehuda, Columbia University, New York City, and Neil Siecke, Swedish Vascular and Heart Institute, Seattle, Washington.
“The opioid epidemic has contributed to a documented decline in life expectancy in the United States in 2016. Although less immediate in its effect on mortality, the cardiovascular effects of methamphetamine may have an appreciable effect on the life expectancy and quality of life of abusers of the drug. MA research and treatment should be a priority, not just of addiction medicine, but of cardiovascular medicine as well,” the editorial writers conclude.
The study authors and editorialists have no relevant disclosures.
JACC Heart Failure. 2018;6:209-218, 219-221. Abstract, Editorial
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