Atrio-Ventricular Nodal Block Associated with Methamphetamine Use

Introduction

Methamphetamine use is a growing public health crisis with significant cardiovascular consequences. Initially developed as a nasal decongestant, its potent stimulant effects and high addictive potential led to widespread abuse. In the United States, methamphetamine use increased significantly between 2015 and 2019, with prevalence rising by 43%, from 1.4 million to 2.0 million users, according to data from the National Survey on Drug Use and Health [1]. Its cardiovascular effects are widespread, including but not limited to hypertension, tachycardia, vasoconstriction, and direct myocardial toxicity, predisposing users to methamphetamine-associated cardiomyopathy (MACM) [2].

MACM primarily manifests as heart failure with reduced ejection fraction (HFrEF), often in younger individuals with chronic methamphetamine use. It is characterized by myocardial fibrosis, oxidative stress, and persistent catecholamine toxicity, leading to progressive left ventricular dysfunction and arrhythmias [3]. While QT prolongation and ventricular arrhythmias are common in methamphetamine users, high-grade AV block, characterized by intermittent failure to conduct 2 or more consecutive P waves, is rarely reported. Here, we present the case of a 40-year-old man with MACM complicated by high-grade AV block, an atypical finding given methamphetamine’s sympathomimetic association with tachyarrhythmias.

Case Report

A 40-year-old man with a 15-year history of inhaled methamphetamine dependence presented to our emergency department with shortness of breath, pedal edema, and intermittent chest pains for 2 weeks. The patient also reported recent inhaled methamphetamine use earlier that day, reporting hypersomnia, agitation, and drug craving, and requested detoxification. He denied any history of cardiovascular disease, including myocardial infarction, arrythmia, or cardiomyopathy, and reported no personal or family history of heart disease. He was not taking any medications and denied use of alcohol, tobacco, or other illicit drugs.

On initial presentation he was in sinus tachycardia at 123 bpm with systolic blood pressure 135/100 mmHg. His temperature was 37°C and oxygen saturation of 99% on room air. Cardiac exam revealed a soft S1, an inferolateral displaced point of maximal impulse, a left ventricular S3 gallop, and a grade 1/6 systolic murmur at the apex. The lungs were clear to auscultation, and there was bilateral pitting edema from the ankle to the mid-shin. A urine drug screen was positive for amphetamines. Laboratory evaluation was notable for an elevated B-type natriuretic peptide (BNP) of 1592 pg/mL and troponin was mildly elevated at 0.06 ng/mL, which down-trended to 0.04 ng/mL without dynamic rise. Test results for common reversible causes of conduction abnormalities were normal, including thyroid function, and electrolyte levels such as potassium, calcium, and magnesium. Semi-upright anterior-posterior (AP) chest radiography revealed moderate enlargement of the cardiac silhouette (Figure 1).

Following a period of sinus tachycardia, the patient developed bradycardia during sleep, coinciding with a brief apneic episode lasting approximately 10 seconds and a delayed oxygen desaturation to 89%. The episode resolved with moderate tactile stimulation and arousal, with return to sinus tachycardia. There were no signs of upper-airway obstruction such as snoring or gasping, and he did not exhibit obesity or craniofacial features typically associated with obstructive sleep apnea. Telemetry captured during this episode initially demonstrated 2: 1 AV conduction, with every other P wave conducted to a QRS complex (Figure 2). Two hours later, a 12-lead electrocardiogram captured a transient episode of 3: 1 AV block preceded by progressive PR interval prolongation across conducted beats (Figure 3). Notably, this episode occurred immediately following a period of sinus tachycardia and was again associated with a short apneic event and oxygen desaturation with return to sinus tachycardia.

Transthoracic echocardiography revealed left ventricular (LV) enlargement with severe global hypokinesis and left ventricular ejection fraction (LVEF) of 20%. He underwent further evaluation with contrasted cardiac MRI, which revealed severe biventricular dilation and dysfunction (LVEF 16%, RVEF 12%) with global hypokinesis, marked left ventricular trabeculation, a hypermobile mass suspicious for LV thrombus, and no late gadolinium enhancement to indicate infarction or scarring, consistent with MACM. Technetium-99m pyrophosphate scintigraphy was also negative for evidence of amyloid disease. Coronary angiography was not pursued, as the resolved chest pain, absence of prior angina or myocardial infarction, and cardiac MRI findings, combined with chronic methamphetamine use, were more consistent with methamphetamine-associated cardiomyopathy than ischemic disease.

The patient was evaluated by the cardiology team for severe non-ischemic cardiomyopathy and was found to have initial sinus tachycardia and symptomatic, rate-dependent, high-grade atrio-ventricular conduction abnormalities, including 3: 1 AV block with progressive PR interval prolongation and 2: 1 AV block. A dual-chamber ICD was successfully placed for primary prevention of sudden cardiac death. He tolerated the procedure well and was discharged in stable condition with plans for outpatient cardiology follow-up.

Discussion

Methamphetamine-associated conduction abnormalities are increasingly observed due to rising methamphetamine abuse among young populations, driven by easy availability, low cost, prolonged stimulant effects, and rapid absorption through smoking or injection. Although methamphetamine toxicity typically presents with tachyarrhythmias, high-grade AV block remains a paradoxical and uncommon finding. This patient’s presentation with dynamic and intermittent high-grade AV block in the setting of severe non-ischemic cardiomyopathy and recent methamphetamine use raises concern for methamphetamine-associated conduction system toxicity, an increasingly recognized complication of stimulant use that can manifest as both arrhythmias and advanced conduction disease.

This phenomenon is mechanistically analogous to the conduction failures observed during isoprenaline (isoproterenol) infusion in pharmacologic stress testing, where sympathetic stimulation enhances AV nodal conduction but may unmask latent disease in the distal His-Purkinje system, resulting in high-grade atrio-ventricular block at elevated heart rates [4].

Blocks distal to the AV node, including intra-Hisian and infra-Hisian block, are clinically significant as they carry a high risk of rapid progression to complete heart block and sudden cardiac death [5]. Definitive localization of the conduction abnormality requires an invasive electrophysiologic study, but several clinical features in this patient raised a strong suspicion for a distal conduction system block. Specifically, the presence of dynamic high-grade AV block, including 3: 1 conduction, with a normal PR interval and narrow QRS complex, and the consistent rate-dependent nature of the block following periods of sinus tachycardia, are features recognized by the American College of Cardiology, American Heart Association, and Heart Rhythm Society as suggestive of intra- or infra-Hisian disease, particularly in the context of structural heart disease or stimulant-associated conduction system injury [6,7].

Given the temporal proximity to recent methamphetamine use, the possibility of drug-induced unmasking or exacerbation of conduction disease warrants consideration. Although amphetamine use was confirmed by urine drug screen, quantitative serum levels were not obtained, limiting assessment of the temporal relationship and exposure severity. Additionally, our patient continued to experience intermittent high-grade AV block throughout his hospitalization, despite supportive care and resolution of acute intoxication.

Myocardial fibrosis, a known complication of methamphetamine abuse, is another potential explanation for conduction abnormalities. Although cardiac MRI did not demonstrate fibrosis, microscopic fibrosis capable of transient conduction disturbances may remain undetected by MRI.

Regarding device management, cardiac resynchronization therapy (CRT) was not pursued due to the absence of left bundle branch block (LBBB) and a QRS duration that did not meet established criteria. While CRT may be considered in patients with high-grade AV block and anticipated frequent pacing, its benefit is most evident when LBBB or wide QRS is present [8,9]. In this case, the absence of persistent bradycardia or sustained AV block made the long-term pacing burden uncertain. Given the severely reduced ejection fraction and ongoing intermittent high-grade AV block, the risk of sudden cardiac death remained elevated. Although guidelines typically recommend waiting at least 3 months of guideline-directed medical therapy before ICD placement in newly diagnosed non-ischemic cardiomyopathy, an exception exists when permanent pacing is urgently required [8,9].

MACM may be reversible with abstinence, but the persistence of conduction abnormalities after resolution of acute intoxication suggested a non-reversible etiology. Thus, ICD implantation was pursued in accordance with current guideline recommendations to address both bradycardia pacing needs and primary prevention of sudden cardiac death. Ultimately, while CRT was not definitively indicated based solely on available data, it may have been the preferred approach to mitigate potential long-term harm associated with frequent RV pacing.

Recognizing methamphetamine-associated conduction abnormalities is increasingly crucial due to escalating methamphetamine use. Patients presenting with heart failure symptoms or arrhythmias, particularly those with drug use risk factors, should prompt consideration of methamphetamine toxicity to ensure early intervention and improved outcomes [10]. Further research is needed to clarify methamphetamine’s effects on the intra-Hisian system and its role in exacerbating distal conduction disease.

Conclusions

Although research is limited, possible mechanisms of methamphetamine-associated heart block include myocardial fibrosis, ion channel remodeling, and disrupted calcium handling. This case emphasizes the significant cardiovascular risks associated with methamphetamine abuse, highlighting the need for greater awareness and early intervention to prevent progression to severe conduction abnormalities.