Methamphetamines are highly addictive CNS stimulants that may be injected, smoked, inhaled, or ingested. They are sympathetic amines that act by elevating the levels of extracellular monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) by promoting their release and blocking their reuptake at the nerve endings [5]. Elevated intrasynaptic monoamine levels affect multi organs encompassing neurological, psychiatric, and cardiovascular complications. The cardiovascular complications of methamphetamine vary from acute life-threatening complications such as malignant hypertension, coronary vasospasm, acute myocardial infarction, aortic dissection, and sudden cardiac death to chronic complications such as methamphetamine associated cardiomyopathy (MACM), pulmonary artery hypertension and right heart failure [2].

Methamphetamine induced hyperadrenergic state stimulates both peripheral alpha and beta adrenergic receptors resulting in hypertension [2]. Although it is recommended to start with alpha antagonist therapy and avoid B-adrenergic antagonist in the acute setting of pheochromocytoma, there are no evidence-based recommendations in the management of methamphetamine induced hypertension. In our case we used Carvedilol which is both an alpha as well as a beta antagonist.

MACM has been classified as dilated, hypertrophic and stress cardiomyopathy. Several case reports have described stress cardiomyopathy (Takotsubo or reverse-Takotsubo pattern) [6,7]. Our case showed dilated MACM with severely dilated left atrium and mild left ventricle dilatation with severely depressed systolic function. MACM has multifactorial and complex pathophysiology. Hyperadrenergic state, coronary vasospasm, ischemia, oxygen free radicals, and direct toxic effect are possible mechanisms of myocardial injury resulting in various pathohistological pictures of atrophy, hypertrophy, fibrosis, myolysis, cellular infiltration and edema [8,9]. A cohort study showed that dyspnea and angina pectoris are the most common symptoms in MACM. Our patient presented with dyspnea and denied any history of chest pain. The same study showed significant improvement of cardiac function and symptoms with discontinuation of methamphetamine abuse together with guideline-directed medical therapy compared to medical therapy only. This was suggested to be dependent on the degree of fibrosis and the irreversible myocytes damage [4]. The decision to implant devices (bi-ventricular pacing or ICD) into patients with MACM should be individualized and incorporate the medical therapy compliance, the likelihood of MA use relapse, and the probability of device infection especially in IV drug users [2].

Methamphetamine abuse is a common risk factor for aortic dissection after hypertension. Several cases have been reported in aortic dissection with MA use [10]. This association is probably secondary to the hypertensive effect. It was recommended to screen for methamphetamine abuse in young patients (less than 50 years old) presenting with aortic dissection [10]. Selective B-blockers as esmolol should be avoided in MA induced aortic dissection to evade the unpredictable effect of adrenergic alpha receptors stimulation. Alpha-antagonists, calcium channel blockers, nitrate, and B-blockers with alpha blocking activity can be used instead [10].

Angina is a common presenting symptom of MA abusers. MA most likely causes myocardial ischemia by similar mechanisms as cocaine which includes coronary vasospasm, thrombus formation, increased myocardial oxygen demand, and direct toxicity. It is unclear that MA is also atherogenic given increased catecholamine release resulting in an increase of blood pressure, platelet aggregation, and shear forces [11]. A pathologic study found that coronary artery disease is more common in MA abusers than controls, however; the former were older than the latter, lessening its reliability [12]. Case reports described MA induced myocardial infarction in the setting of normal coronary arteries, coronary artery stenosis, and significant coronary artery disease indicating different possible mechanisms of MA induced myocardial ischemia [11,13,14]. In our review, we also found three case reports describing myocardial infarction secondary to MA induced coronary artery dissection [15-17]. In patients with chest pain and EKG changes associated with troponin leak, coronary angiography or computed tomography of the coronary arteries should be considered.

Methamphetamine abuse is associated with a high incidence of pulmonary artery hypertension (PAH). This association was found to be in a certain subset of patients indicating genetic and environmental factors involvement. Few pathologic animal studies showed possible mechanisms for Methamphetamine induced PAH. One showed that the 5‐HTT and 5‐HT1B receptor expression was significantly increased in the MA group promoting pulmonary smooth muscle cell proliferation and remodeling of pulmonary arteries and this remodeling was found to be attenuated by fluoxetine (SSRI) [18]. Another Study showed that methamphetamine may promote mitochondrial dysfunction and DNA damage by way of increased oxidative stress in pulmonary artery endothelial cells [19]. Orcholski and his colleagues used whole exome sequencing analysis and identified Carboxylesterase 1, a gene involved in drug metabolism, as a candidate gene for Meth-APAH [20]. Management of Meth-APAH begins with taking a good history and drug screening for patients diagnosed with PAH. Therapy for Meth-APAH is similar to the other form of PAH, however; it showed less response to inhaled nitric oxide challenge predicting less response to certain therapeutic agents as calcium channel blockers [21].