E-cigarettes and cardiovascular health: a review of components, mechanisms, and clinical risk

Abstract

Electronic cigarettes (e-cigarettes) have become one of the most urgent public health issues of the twenty-first century. Originally marketed as less harmful than burning cigarettes, e-cigarettes have gained enormous popularity, especially among young adults, thus leading to nicotine addiction and new trends of cardiovascular damage. Even though e-cigarettes limit exposure to products of combustion, they supply similar doses of nicotine and other elements such as aldehydes, metals, and flavoring by-products, whose cardiovascular effects are incompletely characterized. This narrative review addresses a comprehensive analysis of the cardiovascular effects of e-cigarettes, particularly the contribution to the development of arrhythmias and cardiomyopathy. Evidence was synthesized from in vitro, animal models, and clinical research that covers e-cigarette constituents, delivery mechanisms of toxins, and both acute and chronic cardiovascular effects. E-liquid constituents can result in an autonomic imbalance, increasing heart rate and pressure, conductivity, and the predisposition of arrhythmias and cardiomyopathies. Recent research has shown oxidative stress, endothelial dysfunction, and autonomic imbalance instigated by nicotine and non-nicotinic additives, which destabilize cardiac electrophysiology. However, most human data remain short-term, with limited sample sizes and heterogeneous exposure assessment, underscoring the lack of longitudinal evidence on long-term outcomes such as myocardial infarction, heart failure, or sudden cardiac death. The clinical and public health implications are significant, and it is imperative to shift the focus to vaping as a separate cardiovascular risk factor, particularly among young adults. To reduce the increasing burden of e-cigarette-related cardiovascular disease, preventive actions and enhanced monitoring must be prioritized. They become cardiovascular toxic through nicotine and other chemical exposures, and there is growing evidence of arrhythmogenic and cardiomyopathic effects. Strong prospective studies are urgently needed to define dose-response relationships, long-term outcomes, and cessation strategies.

Introduction

Electronic cigarettes (e-cigarettes or vapes) have rapidly emerged as one of the most debated public health issues in the 21st century. Their impact extends beyond recreational use, increasingly influencing clinical practice in ways that are not fully recognized by many clinicians. The most affected group remains that of adolescents and young adults, which raises urgent concerns regarding prevention and management strategies. Electronic cigarettes were first introduced in 2003 as a less harmful alternative to combustible cigarettes. Consequently, adults who struggled to quit conventional cigarette smoking began reaching out to e-cigarettes, considering them a safer alternative. There were only 7 million users (about twice the population of Oklahoma) in 2011. However, the situation changed rapidly when the prevalence of e-cigarettes rose to 68 million in 2020 and 82 million in 2021 [1].

A combustible cigarette delivers ~1-2 mg of absorbed nicotine, with peak levels in 5-7 minutes. Therefore, a full pack (20 cigarettes) provides approximately 20-40 mg of nicotine. By comparison, a single pod in modern electronic nicotine delivery systems contains 40-59 mg of nicotine, equivalent to or exceeding two packs of cigarettes. Thus, one pod delivers more nicotine than an entire pack of combustible cigarettes [2]. Notably, the introduction of e-cigarettes has reduced cigarette use while maintaining or even increasing nicotine intake, while also introducing multiple harmful compounds [3]. For U.S. adults in 2021, approximately 30.3% of e-cigarette users had never smoked combustible cigarettes [4]. This emphasizes e-cigarettes’ role as an addiction and nicotine delivery source with a complete individualistic presence, separate from combustible cigarettes. E-cigarettes heat a liquid that generally includes propylene glycol, vegetable glycerin, nicotine, and flavorings into an inhalable aerosol. During this process, toxic aldehydes and trace metals are released from the heating elements of the device. These components, along with nicotine, are known to have cardiovascular effects. The exact “recipe” of exposure varies with the device generation, power, liquid composition, and user behavior (length and intensity of a puff). In short, there is no single e-cigarette exposure; there are many. Studies in mice and humans have shown that nicotine, flavoring compounds, and propylene glycol can cause acute increases in heart rate and blood pressure, transient endothelial dysfunction, and changes in vascular biomarker levels [5].

In a murine model, chronic exposure to nicotine-containing e-cigarette aerosol impaired cardiac function, promoted cardiomyocyte structural abnormalities, increased oxidative stress, and accelerated atherosclerosis, highlighting the potential of e-cigarettes to cause serious cardiovascular harm [6]. In an in vitro study, cardiomyocytes exposed to e-cigarette and cigarette smoke extracts showed markedly reduced viability. Exposure to these compounds caused disruptions in all metabolic endpoints, pointing toward potential structural and genetic changes in cells [7,8]. The biggest factor responsible for the rapid rise in e-cigarette use and popularity is misinformation or lack of information. They have been marketed as ‘safer alternatives’ to combustible cigarettes, ‘less harmful’, or even to fight smoking addiction. Emergency departments across the world have reported presentations of adolescents with arrhythmias, high blood pressure, and heart rate and function changes, which only track back to heavy e-cigarette use. Researching the components, mechanisms, and effects of e-cigarette use has become more important. A recent study found that e-cigarette users had significantly longer hospital stays for cardiac issues. On average, it was 2.45 days longer for ever-users and 3.24 days longer for current users than for non-users [9].

These findings underscore a critical gap between public perception and clinical reality. E-cigarettes are frequently dismissed as a benign habit in clinical encounters, yet the cardiovascular burden they impose, even in short-term users, demands that they be treated with the same clinical urgency as conventional tobacco. Although the current evidence based on e-cigarette use remains limited and largely short-term, emerging data suggest potential cardiovascular effects, including arrhythmogenic risk and myocardial dysfunction. In this narrative review, we summarize the current evidence on e-cigarette components, mechanisms of substance delivery, and their potential cardiovascular impact, with a focus on arrhythmias and cardiomyopathy.

Electronic cigarettes

Design of E-cigarettes

Electronic nicotine delivery systems (e-cigarettes) are portable electronic devices designed to deliver aerosolized substances, including nicotine, without causing combustion [10-12]. Evolution of e-cigarette design (Figure 1): (1) Since their introduction, e-cigarette design has evolved considerably across four distinct generations, each reflecting advances in battery capacity, customization, and nicotine delivery efficiency (Figure 1). The earliest devices, known as “cigalikes”, were designed to resemble conventional cigarettes closely and were either disposable or used pre-filled cartridges [13]. The second generation, commonly referred to as “vape pens”, introduced larger battery capacities, refillable tank systems, and adjustable voltage settings that allowed users greater control over vapor production [13]. (2) Third-generation devices, or “mods”, expanded on this further with highly customizable designs, larger e-liquid capacity, and the incorporation of sub-ohm coils that enabled significantly increased aerosol output [12,13]. (3) The most recent fourth-generation devices, known as “pod systems”, represent a shift toward compactness, using closed or refillable pods that typically deliver higher concentrations of nicotine salts - JUUL products being among the most widely recognized examples [12,13].

Figure 1.

Types of e-cigarette devices. From left to right, this figure shows the first-generation “cigalike”, second-generation or “vape pen”, third-generation “box mod”, and fourth-generation “pod system”.

The vaporization process begins when the e-cigarette is activated, in most models, by either pressing a button or automatic breath activation, which triggers the flow of electrical current from the battery to the heating coil [14]. The heating coil vaporizes the e-liquid stored on the wick, and the resulting aerosol produced from the coil is inhaled through the mouthpiece of the device [10,15].

E-cigarettes share a handful of core components that determine their functioning and safety characteristics while in use (Figure 2) [11,14]. The primary power source is typically a lithium-ion battery. Most advanced devices offer adjustable voltage and wattage options, which influence the aerosol temperature and the composition of the aerosol [10,15].

Figure 2.

E-cigarette parts. The illustration identifies key elements of an e-cigarette, including a mouthpiece, cartridge with e-liquid, atomizer [heating element], battery, and LED indicator.

The heating coil is commonly made of kanthal, nichrome, or stainless steel, with its resistance [in ohms] defining the temperature and volume of the vapor produced. Studies have indicated that higher temperatures increase the formation of undesirable carbonyl compounds, including formaldehyde and acrolein [10,15].

The wick, made of cotton, silica, or ceramic, is a pathway for the e-liquid to move from the reservoir to the heating coil [14]. The wick material can change the amount of thermal degradation byproducts. E-liquids are stored in various types of reservoirs, including cartridges, tanks, or pods [14,15].

Constituents in E-cigarette liquids and emissions

The e-liquid typically contains nicotine in varying concentrations, dissolved in carrier solvents such as vegetable glycerin (VG) and propylene glycol (PG), blended in various PG/VG ratios [16]. Additional constituents may include flavoring agents, N-nitrosamines, volatile organic compounds, and trace metals (e.g., cadmium, chromium, lead, nickel, silver, tin, and silicates) that can leach from device components such as coils, wicks, and solder joints [17,18].

Upon heating, the e-liquid is aerosolized into an inhalable mixture of nicotine, solvents, and flavoring compounds [19]. Nicotine and toxicant delivery are influenced by device settings (e.g., voltage/power), e-liquid composition (including PG/VG ratio and pH), and user puffing behavior (puff duration, volume, and frequency) [20]. The PG/VG ratio affects aerosol particle size and nicotine yield, while e-liquid pH determines the proportion of free-base versus protonated nicotine, influencing absorption characteristics [21]. Commercial formulations range from 0 to >36 mg/mL nicotine, with some capable of delivering nicotine doses comparable to or exceeding those of conventional cigarettes [20].

Nicotine

Nicotine is the primary psychoactive and addictive component responsible for many of the cardiovascular effects of e-cigarettes. It is rapidly absorbed through the oral mucosa and pulmonary epithelium and readily crosses the blood-brain barrier, where it binds to nicotinic acetylcholine receptors (nAChRs). This interaction stimulates the release of neurotransmitters, including dopamine, norepinephrine, serotonin, γ-aminobutyric acid (GABA), glutamate, and endorphins. Dopamine release, in particular, activates central reward pathways, contributing to nicotine dependence [22,23].

Nicotine also activates the sympathetic nervous system, leading to increased heart rate, blood pressure, and cardiac output. Sustained sympathetic stimulation contributes to arrhythmogenesis, including atrial fibrillation and ventricular tachycardia, and may increase the risk of sudden cardiac death. It also promotes myocardial remodeling, thereby increasing the risk of heart failure [22,24]. Nicotine-induced catecholamine release accelerates atherosclerosis and exacerbates dyslipidemia by promoting lipolysis, increasing plasma free fatty acids, reducing high-density lipoprotein cholesterol, and elevating low-density lipoprotein cholesterol [25]. In addition, upregulation of vascular growth factors, including platelet-derived and vascular endothelial growth factors, contributes to endothelial dysfunction, oxidative stress, fibrosis, and arterial stiffness [24]. Although nicotine plays a central role in these effects, overall cardiovascular risk is also influenced by variability in nicotine delivery, as well as potential contributions from other e-cigarette constituents.

Nicotine delivery and device variability

Nicotine delivery from e-cigarettes is governed by interactions between device characteristics, e-liquid formulation, and user behavior. Newer-generation devices, particularly pod-based systems, are capable of achieving higher plasma nicotine concentrations than earlier models [26]. Early e-cigarettes primarily use free-base nicotine, an unprotonated, more lipophilic form (pH~7-9) that facilitates membrane diffusion but produces greater inhalation harshness, thereby limiting tolerable concentrations [27]. In contrast, modern devices commonly use protonated nicotine salts, which are more hydrophilic and have a lower pH. This reduces sensory irritation, enabling higher nicotine concentrations and deeper inhalation [27].

For example, studies of JUUL have shown that a single 5% nicotine pod can deliver nicotine amounts comparable to up to ~30 cigarettes, depending on user puffing patterns and formulation characteristics [2,11]. Lower pH aerosols favor smoother inhalation and deeper lung deposition, enhancing systemic absorption, whereas higher pH promotes the gaseous phase, increasing upper airway absorption but also harshness [22,27]. In contemporary nicotine salt-based systems, nicotine exposure is primarily driven by puff topography and device power output, with longer puff duration, greater puff volume, and higher power significantly increasing systemic nicotine delivery [28].

Solvents

The main ingredients in e-liquid are propylene glycol and glycerol. These act as solvents that dilute nicotine to the right concentration and give it the viscosity needed for vaporization (varying PG/VG ratios). When heated, these substances break down and release various harmful aldehydes and related byproducts. Glycerol can produce acrolein, formaldehyde, and dehydrated glycerol, while propylene glycol can create acetaldehyde, formaldehyde, propylene oxide, acetol, allyl alcohol, glyoxal, and methylglyoxal [29,30]. Formaldehyde is particularly dangerous for myocytes. It has been linked to cardiovascular issues such as atrioventricular block, different arrhythmias, ventricular tachycardia, ventricular fibrillation, and atrial fibrillation. The reactive aldehyde acrolein can increase thrombosis risk by worsening dyslipidemia, speeding up atherosclerosis, altering apolipoprotein A-I in high-density lipoprotein, promoting inflammation from neutrophils, and increasing platelet activation [31,32]. Both acrolein and formaldehyde cause toxicity partly by forming adducts with DNA and proteins [32].

In animal studies, acetaldehyde has been tied to mitochondrial issues that lead to alcoholic cardiomyopathy [33]. Device features influence the generation of these aldehydes. A higher battery voltage significantly raises aldehyde emissions, sometimes matching or exceeding those of combustible cigarettes [34]. Reusing devices can further increase aldehyde production, likely due to the breakdown of built-up polymerization products [35].

Besides aldehydes, aerosolized vegetable glycerin has been associated with irritation in the esophagus, lungs, and eyes. Propylene glycol exposure has been linked to symptoms affecting the upper respiratory tract [36]. The ratio of propylene glycol to vegetable glycerin in e-liquids also impacts the production of reactive oxygen species. These species are connected to atherosclerosis, hypertension, restenosis, and ischemia [37]. The amount of propylene glycol also affects nicotine delivery; larger amounts are linked to greater nicotine yields. However, establishing a clear quantitative link is made difficult by the variety among brands and the differences between labeled and actual solvent ratios [26,29].

Flavorings

E-liquid flavorings commonly include chemicals such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine [38]. These appealing flavors are key drivers initiation of e-cigarette use among youth [39]. Flavoring agents are not biologically inert; even in the absence of nicotine, they have been shown to induce inflammation, oxidative stress, and DNA damage, along with endothelial dysfunction and epithelial barrier disruption. Additionally, they may cause electrophysiological alterations, immunomodulatory effects, and adverse cardiovascular outcomes, including impaired nitric oxide signaling, altered vasoreactivity, arrhythmias, and reduced cell viability.

Notably, many flavoring compounds carry ‘Generally Recognized as Safe’ status for oral ingestion, yet this designation was never intended to cover inhalation. This regulatory blind spot represents a fundamental failure of pre-market safety evaluation for e-cigarette constituents, and highlights that the absence of regulation should not be conflated with the absence of harm.

Nitrosamines

Tobacco-specific nitrosamines [TSNAs] are potent carcinogens found in tobacco products, including some e-cigarette liquids and aerosols. They can damage DNA and cause mutations, leading to lungs, mouth, and several other cancers [40]. The formation of TSNAs increases with time and at higher temperatures, which can provide important information for evaluating and ensuring the quality of e-cigarette products [41].

Metals

Studies have shown that e-cigarette vapor can contain toxic metals such as lead [Pb], nickel [Ni], chromium [Cr], and cadmium [Cd] [42]. E-liquids that touch the heating coils often have higher amounts of metals than e-liquids straight from the bottle. This occurs because parts inside the device, such as wires and clamps made of metals such as copper, silver, and nickel, can release these metals into the liquid. For example, copper wires with silver coatings and brass clamps are linked to more metals, such as zinc and aluminum, which appear in the vapor that people inhale. Inhalation of these metals is a health concern because they are poisonous; lead and Cd are known carcinogens, and Ni or Cr can harm the lungs, heart, kidneys, and nervous system [43].

Mechanisms of cardiovascular injury

The increased presence of ECs is one of the troubling emerging world trends at present, as it lacks longitudinal data on its safety and health impacts, and they are being suggested as alternatives that are less damaging [44,45]. Multiple flavored e-liquids and typical flavoring agents were found to cause deterioration of endothelial cell functionality in vitro [6,46]. Endothelial cells generated from pluripotent stem cells show reduced viability, tube formation, and wound healing (e.g., a scratch test) upon exposure to cinnamaldehyde and menthol, as observed in flavored e-liquids, and upregulate the expression of inflammatory cytokines [6]. Cinnamaldehyde and vanillin promote inflammatory cytokine and chemokine production by endothelial cells exposed to flavored e-liquid or RY-4 e-liquid. Vanillin, menthol, cinnamaldehyde, eugenol (clove flavoring), and acetylpyridine (burnt flavoring) accelerate the production of interleukin-6 and inhibit A23187-mediated nitric oxide production in human aortic endothelial cells [6]. In standing e-liquid, the reaction between flavor aldehydes and propylene glycol or glycerin may produce toxic acetals. These acetals, in turn, cause more respiratory irritation than the original aldehyde [47,48].

Large systemic doses of propylene glycol (more than the suggested maximum dose of 25 mg/kg-1∙d-1) may induce severe metabolic acidosis, acute kidney injury, and sepsis-like conditions [49]. Theatrical fog and smoke are generated via glycol mixtures, and occupational exposure to glycol mixtures at work is linked to increased reports of glycol wheezing and tightness in the chest [50,51]. Acute effects of glycol mixture exposure include acute dry cough, throat irritation, and lung impairment in heavily exposed individuals [51]. In vitro exposure of pulmonary epithelial cells and monocytes to aerosols generated with each of the flavored JUUL pods raised levels of inflammatory cytokines, generated mitochondrial oxidants, increased DNA damage, and disrupted pulmonary epithelial barrier integrity [52]. Exposure of human bronchial epithelial cells to the flavoring agents acetoin (presenting a buttery taste), diacetyl, ortho-vanillin, and maltol (malt taste) after 24 hours showed an increase in interleukin-8 production, indicating that the flavoring agents act independently to induce toxicity.

The long-term cardiovascular and cardiopulmonary consequences remain largely undefined due to the absence of longitudinal human data. This gap has contributed to the widespread perception of ECs as a safer alternative to combustible cigarettes. However, as discussed above, accumulating experimental and short-term clinical evidence suggests that this perception may be premature. Many of the chemical constituents used in EC liquids have well-established toxic, pro-inflammatory, and pro-atherogenic effects when studied individually. Their repeated inhalational exposure, often at high concentrations and over prolonged periods, raises concern for delayed but clinically significant cardiovascular pathology that may only become apparent after years or decades of use.

Before examining how these mechanisms translate into clinical outcomes, it is useful to clarify how electronic cigarettes differ from combustible cigarettes, as the two are often grouped together despite delivering nicotine through fundamentally different processes. A combustible cigarette burns tobacco at elevated temperature, and this combustion produces smoke carrying tar, carbon monoxide, and thousands of byproducts that drive much of the cardiovascular harm linked to conventional smoking. An electronic cigarette instead heats a liquid to generate an inhalable aerosol without igniting tobacco, thereby removing tar and greatly reducing carbon monoxide exposure. This difference, however, is not the same as safety. Heating introduces a distinct toxicological burden, including reactive aldehydes formed as solvents degrade, flavoring chemicals that were never assessed for inhalation, and trace metals shed from the heating coil and other device parts. Nicotine delivery complicates the comparison further, since modern pod systems using nicotine salts can reach plasma nicotine levels that match or exceed those of combustible cigarettes, meaning the move from smoking to vaping does not reliably reduce, and may even raise, nicotine intake. A final and often overlooked difference is predictability: combustible cigarettes are uniform products, whereas the chemical output of an electronic cigarette shifts with device generation, power setting, solvent ratio, flavoring, and individual puffing behavior.

Taking together, these differences suggest that e-cigarettes and combustible cigarettes share a broadly overlapping cardiovascular mechanism, rooted in nicotine-mediated sympathetic activation, oxidative stress, and endothelial injury, while diverging substantially in chemical composition, nicotine delivery dynamics, and the degree to which any given exposure can be predicted or standardized. To organize these points of overlap and divergence systematically across the principal domains of cardiovascular injury, and to establish the comparative framework that informs the mechanistic and clinical discussion that follows, the key characteristics of both product types are summarized in Table 1.

Table 1.

Comparative cardiovascular effects of e-cigarettes and combustible cigarettes

Domain	E-cigarettes	Combustible cigarettes
Particle Profile	Lower total aerosol particle mass, but aerosol contains ultrafine particles, thermally degraded aldehydes (e.g., formaldehyde, acrolein), flavoring-related toxicants, and trace metals leached from heating components [18]	High levels of fine particulate matter, tar, oxidants, and established carcinogens generated through tobacco combustion [19]
Nicotine Delivery	Variable; modern pod-based systems using nicotine salts can match or exceed combustible cigarette levels; highly dependent on device generation, power setting, and puffing behavior [2,30]	Relatively standardized; approximately 1-2 mg absorbed per cigarette; peak plasma levels reached within 5-7 minutes [2]
Processing	Heating of e-liquid produces an inhalable aerosol without combustion; carbon monoxide exposure is minimal [10,15]	Combustion of tobacco at high temperatures produces tar, carbon monoxide, and thousands of toxic byproducts [19]
Arterial stiffness	Increased pulse wave velocity and augmentation index; effects observed even in the absence of nicotine, suggesting a contribution from non-nicotine aerosol constituents [101,107]	Significant and well-established increase in arterial stiffness and vascular resistance with chronic exposure [101,107]
Oxidative Stress and Inflammation	Acute ROS generation from heated PG/VG and flavoring chemicals; mitochondrial oxidative stress and DNA damage; early endothelial dysfunction without established atherosclerosis [90,91]	Persistent ROS exposure from combustion products; oxidative LDL modification and foam cell formation; chronic endothelial injury leading to progressive atherosclerosis [37]
Hemodynamic effects	Acute increases in heart rate, blood pressure, and sympathetic activation; magnitude generally less sustained than combustible cigarettes [63,64]	Sustained increases in heart rate and blood pressure with chronic autonomic imbalance and persistent sympathetic overdrive [24]
Carbon monoxide exposure	Minimal, due to the absence of combustion; does not contribute meaningfully to hypoxic cardiovascular injury [10,15,19]	High exposure from tobacco combustion; contributes to tissue hypoxia, impaired oxygen delivery, and vascular injury [19]
Clinical cardiovascular risk	Limited long-term data; emerging associations with cardiovascular dysfunction, arrhythmias, and endothelial injury; causal relationships not yet established [101-103]	Strong and well-established association with myocardial infarction, stroke, heart failure, and cardiovascular mortality across decades of prospective cohort data [100]
Overall interpretation	Not without risk; causes measurable acute vascular and electrophysiological dysfunction; long-term cardiovascular harm plausible but incompletely characterized	A major, well-characterized cardiovascular risk factor with robust epidemiological evidence supporting causal harm across multiple endpoints

Abbreviations: ROS, reactive oxygen species; PG, propylene glycol; VG, vegetable glycerin; LDL, low-density lipoprotein; CO, carbon monoxide.

Table 1 places the two products side by side across domains including particle profile, oxidative stress, hemodynamic effects, and clinical cardiovascular risk. However, one distinction the table cannot fully capture deserves emphasis. The evidence base for combustible cigarettes spans decades of large prospective cohort studies with hard clinical endpoints such as myocardial infarction and cardiovascular mortality. For e-cigarettes, the equivalent evidence simply does not exist yet. Drawing direct comparisons, therefore, risks either falsely reassuring users that e-cigarettes are safer, or overstating risk in ways that undermine cessation efforts for conventional smokers.

Cardiovascular effects of E-cigarettes

As discussed earlier, exposure to nicotine, aldehydes, metals, and other aerosolized toxicants has been shown to disrupt autonomic balance, impair vascular function, and promote electrophysiological instability [47,53]. However, toxicological plausibility alone does not establish clinical relevance. Therefore, beyond the experimental and mechanistic data on individual e-liquid constituents, it is critical to examine whether these effects translate into documented cardiovascular pathology in humans. This section reviews the available clinical and observational evidence linking e-cigarette use to arrhythmias and cardiomyopathy, with a particular focus on reported cases, physiological alterations, and early signals of myocardial dysfunction that may substantiate the mechanistic concerns raised by constituent-level studies.

Arrhythmias

The rhythmic contraction of the heart is highly dependent on coordinated electrical activity, which begins in the sinoatrial (SA) node and propagates through the atria, reaching the atrioventricular (AV) node, the His-Purkinje cell system, and the rest of the ventricular myocardium [54,55]. At a cellular level, electrical conductivity begins with the activation of an action potential, regulated by fluxes of sodium (Na⁺), calcium (Ca²⁺), and potassium (K⁺) across ion channels and transporters [56]. This orchestration ensures depolarization and repolarization in a regular sequence, allowing effective excitation-contraction coupling to occur. This process can be viewed through an electrocardiogram (ECG), appearing as the P wave (atrial depolarization), PR interval (AV-nodal conduction), QRS complex (ventricular depolarization via fast Na⁺ influx), and T wave [ventricular repolarization, reflecting K+ currents and late Na⁺/Ca²⁺ dynamics]. Disruption of any of these parts can result in abnormal heartbeats, formally known as arrhythmias or dysrhythmias [57,58].

Recent studies have indicated that e-cigarettes can induce multiple perturbations in cardiovascular activity that closely resemble those observed with conventional tobacco smoking. Clinical findings have shown that e-liquid constituents induce cellular distress and autonomic imbalance, destabilizing the electrophysiological current that sustains the normal rhythm [59-62]. These disturbances translate clinically into irregularities in heart rate (HR), blood pressure (BP), and heart rate variability (HRV) [45,63,64]. Experimental data suggest that e-cigarette aerosols can depolarize the resting membrane potential, increase heterogeneity of repolarization, and furthermore, the susceptibility to arrhythmias (view Figure 3). When combined with common triggers, such as premature ventricular beats (PVBs), re-entry circuits, or abnormal automaticity can occur, leading to tachyarrhythmias, fibrillations, and other conduction disturbances. In this way, e-cigarette exposure may mimic and amplify the arrhythmogenic potential originally only attributed to tobacco smoking.

Figure 3.

Main triggers in e-cigarette aerosol lead to cardiac arrhythmia. The main constituents in e-cigarette aerosol (nicotine, flavorings, solvents) provoke inflammation, autonomic imbalance, and alterations in cardiac action potential through ion channel disruption. These mechanisms lead to oxidative stress, cytokine release [interleukin-6 (IL-6), interleukin-8 (IL-8)], myocardial remodeling, and conduction abnormalities, which increase the risk of several types of arrhythmias.

Tachyarrhythmias induced by E-cigarettes

Rapid heart rhythms over 100 bpm are known as tachycardias or tachyarrhythmias, which can originate from disruptions in the impulse generation [automaticity], conduction, or myocardial repolarization [57,58]. This group contains the most common types of arrhythmias and can be subdivided into supraventricular arrhythmias (SVT) and ventricular arrhythmias (VT). Where SVT typically presents a narrow QRS complex on ECGs [65], while VT is represented by a wide QRS complex [66]. Emerging studies suggest that e-cigarettes can lead to cellular ion exchange abnormalities [67], increased heart rate variability (HRV) [68,69], modification in repolarization [70], and boosting ventricular premature beats (VPB) [71]. These findings suggest that e-cigarette exposure can generate the electrophysiological setting that favors both SVT and VT.

Recent evidence places nicotine in the central role for the arrhythmogenic effects of e-cigarettes. Upon inhalation, nicotine is rapidly absorbed into the bloodstream, binding with nicotinic acetylcholine receptors (nAChRs), and activating catecholamine release in peripheral sympathetic nerve terminals and adrenal chromaffin cells [60,71]. This commences the shift to a dominance of sympathetic activity that reduces parasympathetic action [71,72]. Further studies demonstrated that in humans, the binding of nicotine to nAChRs decreased acetylcholine release and M2 receptor activation, blocking inward rectifying K⁺ channels coupled with G-protein, thus obstructing the dromotropic modulation in cardiomyocytes by the parasympathetic system [67]. The reduced modulation shortens the PR interval, which results in a briefer refractory time in the AV-node and therefore a rapid AV conduction. This last mechanism especially favors reentrant supraventricular tachycardias (AVNRT).

The β1-adrenergic dominance due to nicotine leads to the excretion of catecholamines such as dopamine and norepinephrine, which increases heart rate and contractility [67,73]. However, human studies have shown that dopamine is the primary mediator in accelerated AV conduction by shortening both the PR interval and the segment, leading to supraventricular tachyarrhythmias [67]. This effect on the augmentation in conduction velocity by catecholamines is also prolonged by nicotine through the partial suppression of catecholamine breakdown via inhibition of monoamine oxidase [74]. Following a similar mechanism, the nicotine-induced sympathetic overdrive is also involved in ventricular tachyarrhythmias and sudden death risk [63,75]. A study in healthy e-cigarette users and non-users showed an increased Tp-e/QT ratio on ECGs after e-cigarettes with nicotine exposure [63]. This prolongation of the Tp-e/QT ratio suggests a dispersion of ventricular repolarization that could be used as a marker for ventricular tachycardia, fibrillation, and sudden death [63,76,77].

It is important to note that the formulation of nicotine appears to influence the arrhythmogenic risk [59,77]. Current research has demonstrated that systems with nicotine salts deliver nicotine more efficiently and with less irritation, increasing plasma concentration compared to free-base nicotine [78,79]. In mice, nicotine salts, especially at 5%, increased HR and decreased HRV at a greater level than those with 1% and 2.5%, though all increased the risk for VPB compared to air [59]. Nonetheless, randomized clinical studies have shown that 5% vs 2.4% nicotine delivery systems have no clinically relevant difference in HR or BP, likely due to real-life puff volume variation [80]. Both studies corroborate the tilt toward the β1-adrenergic pathway through nicotine-induced ion-channel inhibition and heightened risk of ventricular tachyarrhythmias.

Separately, non-nicotine constituents such as flavor aldehydes, solvent vehicles, and byproducts also affect cardiac conduction [71,72]. Evidence shows e-cigarette liquid containing both menthol and nicotine (as in JUUL-type pods) provoked higher VPBs than those with nicotine or menthol alone [71]. This is relevant because accelerated atrial conduction, but prolonged AV conduction indicates a synergistic and pro-arrhythmic interaction. Other products, such as vegetable glycerin (VG) and propylene glycol (PG), which are solvent vehicles, when observed separately from nicotine, studies showed an initial parasympathetic dominance, measurement post-exposure exhibited tachycardia and lower HRV, probably due to a sympathetic rebound shift [71,81].

Fibrillation induced by E-cigarettes

Cardiac fibrillations are the most common type of arrhythmias, with complications like strokes and life-threatening risks [81,82]. Both forms, atrial and ventricular, distinguish themselves from tachycardias by their chaotic or irregular rhythm, which results in critically impaired cardiac output and, on many occasions, sudden death [75]. On the ECG, atrial fibrillation (AF) is characterized by the absence of P waves and irregular R-R intervals [83], while ventricular fibrillation (VF) is characterized by low-amplitude oscillations without abnormal QRS complexes [84]. Both forms are commonly associated with cellular damage and structural remodeling [fibrotic], creating a medium with poor conduction sustaining abnormal reentry and automaticity [57,85]. The latest data show that e-cigarette exposure harms the cardiovascular musculature by intra- and extracellular mechanisms [6].

Nicotine itself drives a feed-forward injury loop by upregulating the phosphatase PHLPP1 via an ERK1/2-4E-BP1 signaling axis, which in turn amplifies NADPH-oxidase-derived reactive oxygen species (ROS) and mitochondrial dysfunction, leading to cardiomyocyte death [61]. The resulting oxidative stress destabilizes calcium-handling proteins (RyR2, SERCA, L-type Ca²⁺ channels) and gap-junction connectivity, shortens action-potential duration, and promotes both atrial and ventricular fibrillation [86-88]. Moreover, oxidative stress-induced ROS can further activate pro-fibrotic pathways, contributing to structural remodeling that predisposes to atrial fibrillation. Several studies implicate nicotine-mediated suppression of microRNAs (e.g., miR-133, miR-590) in fibrotic remodeling by causing a greater deposition of collagen; further investigations must be conducted in humans [89]. Together, excessive ROS production, PHLPP1, mitochondrial injury, and consequent electrophysiological derangements create a potent substrate for fibrillatory arrhythmias in e-cigarette users.

Although widely used compounds such as vanillin and cinnamaldehyde are growing in popularity, there is a lack of safety regulation for inhalation use, despite being recognized as safe for ingestion [98,99]. This is thought to be due to the generation of reactive aldehydes after the aerosolization process, which new evidence indicates to have direct cardiotoxic and pro-arrhythmic contribution [6,99,100]. Studies show that exposure to these aldehydes increases the ROS production, impairs mitochondrial membrane potential, and amplifies electrical instability [6,101]. The cinnamon-flavored e-liquid has been identified as the most cytotoxic among the rest [100]. In acute exposure, cinnamaldehyde has elevated ROS, reduced endothelial cell viability, activates apoptotic pathways, and impairs angiogenesis [6,102].

The heterogeneity of flavoring compounds across e-cigarette products makes population-level risk assessment particularly difficult. Unlike nicotine, whose concentration can be measured and regulated, the flavoring landscape is vast, largely unregulated, and rapidly evolving. A user switching brands or flavors may unknowingly alter their arrhythmogenic risk profile in ways that neither they nor their clinician can anticipate. This represents a unique challenge that has no direct parallel in conventional tobacco regulation.

Bradyarrhythmia induced by E-cigarettes

As opposed to the rapid and chaotic heartbeats of tachyarrhythmia and fibrillation, bradyarrhythmia or bradycardia are atypical slow conduction beats, with HR lower than 60 bpm [58]. Commonly due to a suppression of nodal activity or overcompensation of the parasympathetic tone. The two categories are sinus bradycardia and atrioventricular conduction blocks (first, second, third degree) [81]. Kucera et al. [59] demonstrate that free-base nicotine at 5% increased HRV without raising the HR, which suggests a parasympathetic reaction. Similarly, Carll et al. [71] describe how VG and PG aerosols separately and without nicotine cause bradycardia, bradyarrhythmia, and increased HRV during inhalation.

This parasympathetic tilt, as opposed to the ones seen with nicotine, could be due to acrolein generation in the VG and PG smoke. Acrolein inhalation activates airway sensory nerves (TRPA-1), triggering a vagal reflex acetylcholine release at the SA and AV nodes, hence more M₂ receptor activation. Particularly, VG aerosols cause even more pronounced bradycardias and bradyarrhythmia -as high-grade supraventricular blocks-, which could be explained because it has higher acrolein levels as opposed to PG aerosols [71]. There is also evidence that PG aerosols alone can cause aortic endothelial dysfunction, by making the smooth muscle in the vessel wall less responsive, increasing the risk factor for arrhythmia and other CVDs [95]. On the other hand, vegetable glycerin (VG) and propylene glycol (PG), which are solvent vehicles, when observed separately and without nicotine, showed an initial parasympathetic dominance, measurement post-exposure reversed tachycardia and lower HRV, probably due to a sympathetic rebound [71,96].

The biphasic autonomic response observed with solvent exposure, initial parasympathetic dominance followed by sympathetic rebound, is particularly clinically relevant. It suggests that the cardiovascular risk of e-cigarettes is not static but dynamic, shifting across the exposure timeline. Standard acute measurement protocols likely capture only one phase of this response, which may explain some of the contradictory findings across studies and warrant investigation through continuous ambulatory monitoring designs.

Cardiomyopathy

Cardiomyopathy is an anatomical and pathological diagnosis associated with muscular or electrical dysfunction of the heart [97]. There are three major types of cardiomyopathies: restrictive, dilated, and hypertrophic. It often leads to heart failure, arrhythmias, ischemic heart disease, and sudden cardiac death. Though nicotine is an established risk for cardiomyopathy, data are still limited to e-Cigarettes as the cause. This is predominantly because of the recent introduction (2004 in China and 2006 in the US) and limited longitudinal studies conducted on vapers. Recent evidence, however, uncovers a link between toxic chemical exposure from e-cigarettes and long-term effects on cardiovascular function. There are a range of interconnected pathophysiological mechanisms proposed. The primary ones are endothelial cell dysfunction and oxidative stress. There are also considerations of vascular injury and inflammation. Short-term e-cigarette use in non-smokers can lead to reduced myocardial perfusion, ischemia, and fibrotic remodeling over time, leading to cardiomyopathy.

Preliminary studies in mice have been conducted by developing a model that delivers chemicals in mice like those of human e-cigarette users. E-cigarettes of concentrations of 2.4% [A] and 0% [B] were used. Echocardiography studies at 12 weeks showed a decreased left ventricular ejection fraction of 60±2% in the 2.4% group [A] against 70±7% of the 0% group [B]. LV fractional Shortening in the 2.4% [A] group was 27±1% compared to 34±4% in the 0% group [B]. Ventricular Transcriptomic analysis revealed changes in genes associated with metabolism, circadian rhythm, and inflammation in the 2.4% mice group [A]. Transcription electron microscopy also uncovered that cardiomyocytes of mice in the 2.4% group [A] indicated microstructural abnormalities suggestive of systolic dysfunction without hypertrophy or diastolic impairment; suggestive of early changes of cardiomyopathy [7].

One in vitro study conducted on Human Induced Pluripotent Stem Cell-derived Cardiomyocytes (hiPSC-CM) demonstrates that e-cigarette extract (ECE) and cigarette smoke extract (CSE) both prolong calcium decay time and increase time to peak calcium. This indicates slower clearance and impaired handling of calcium within heart muscles. This has eventually demonstrated a reduction in contraction amplitude. A 48-hour exposure to smoke extracts raised cardiomyocyte apoptosis and cell death rates. These findings suggest that e-cigarette-derived toxicants impair cardiomyocyte calcium cycling, contractility, and viability, thereby giving evidence of progression to cardiomyopathy [9].

All the human data we have is a few case reports. These cases are especially concerning because they have happened in otherwise healthy people after acute e-cigarette use. A healthy 35-year-old bodybuilder developed severe dilated cardiomyopathy with an ejection fraction of 32%. He presented with heart failure and EVALI. All other causes were ruled out, supporting e-cigarettes as the most probable etiology of his condition [98]. Another case series showed 2 patients (42-year-old and 48-year-old), developing non-ischemic cardiomyopathy after 1 and 3 months of use, respectively [99].

The existence of cardiomyopathy cases in otherwise healthy young individuals following e-cigarette use is striking, but the evidence base remains too sparse to establish causality. The fundamental challenge is that cardiomyopathy develops over months to years, while the longitudinal studies needed to track this progression in e-cigarette users do not yet exist. Clinicians are therefore left in the uncomfortable position of managing a plausible but unquantified risk. In this context, a high index of suspicion is warranted - particularly in young patients with unexplained cardiac dysfunction and a vaping history - even in the absence of definitive population-level proof.

Limitations of current evidence

Despite increased interest in the cardiovascular consequences of e-cigarette use, current evidence is restricted by methodological challenges. Recent studies have accurately recompiled acute or short-term effects (HR, BP, ECG intervals) in both animals and humans; long-term follow-up for clinical outcomes such as arrhythmias, myocardial infarction, or cardiomyopathy is still scarce [92,100]. The follow-up periods are often short, given the recent introduction of e-cigarettes, making multi-decade cohort data unavailable [101]. Another limiting factor is the variability of dosing protocols, which results in inaccurate real-world exposure recreation, obscured cumulative dose-response effects or progressive cardiac remodeling, and poor generalization of outcomes. Another significant limitation is variation in device characteristics and e-liquid formulations. The variability in nicotine concentration, solvent ratios, flavor additives, and heating coil composition affects the delivery of toxicants such as aldehydes and metals, making cross-study comparability and generalizability difficult.

Much of the research available now is on preclinical in vitro or animal studies, such as isolated cardiomyocytes and rodent exposures, which can only mimic human autonomic regulation or the long-term remodeling to a certain point [89]. Most clinical studies are often small, limiting generalizability. The PATH longitudinal study found no association between e-cigarette exclusive use and cardiovascular disease; this could have been due to the low number of e-cigarette exclusive users and poor reliance on self-reported myocardial infarction and stroke [102]. Perhaps the most fundamental limitation is the mismatch between the pace of e-cigarette market evolution and the pace of scientific investigation. New device generations, nicotine salt formulations, and flavoring compounds reach consumers years before their cardiovascular effects can be meaningfully studied. This means the evidence base will perpetually lag real-world exposure, placing clinicians and regulators in a position of making consequential decisions under chronic uncertainty. Acknowledging this structural limitation is essential to interpreting the current literature honestly.

Public health and clinical implications

E-cigarette use has been associated with rapid heart rate and an increase in blood pressure, oxidative stress, and endothelial damage and inflammation, which are well-established as evident from recent research and reviews [93,94,103-106]. The scientific statements of the American Heart Association reported that youth who use E-cigarettes show rapid hemodynamic changes, increased arterial stiffness, and arterial dysfunction, with concerns that these effects can accumulate and add to their long-term cardiovascular risk [101,107]. These side effects are associated with nicotine but also with other compounds such as flavorings and aldehydes [104,106,108].

Although some studies indicate that the transition from traditional combustible cigarettes to e-cigarettes can yield modest benefits in select cardiovascular measurements, such as circulation and blood pressure, particularly in the younger population, e-cigarettes are not devoid of risk, and they may still produce a pro-atherosclerotic, pro-arrhythmogenic, and other cardiovascular effects [89,103,105,108]. The lack of long-term safety data on e-cigarettes, as well as the high rates of continued use, are given as reasons why the American College of Cardiology, in its joint guideline, does not recommend e-cigarettes as first-line therapy to assist with smoking cessation, and calls for further research into quitting strategies and CVD effects [109]. Consensus statements from the American Heart Association and other societies have clarified that e-cigarettes are not a safe alternative to conventional tobacco use, particularly for youth and non-smokers, and have called for immediate long-term epidemiological studies [101,107,109]. Key controversies and gaps include paucity of long-term data, differences in device compositions, and uncertain effects of chronic exposure, especially in adolescents and dual users [101,103,106,110].

E-cigarettes are not beneficial to cardiovascular health and are associated with an increased risk of hypertension, arrhythmias, and cardiovascular disease, particularly in young people. Complete cessation of all forms of tobacco products is best for smokers, with FDA-approved cessation medications safer than e-cigarettes and having the most current, best evidence base for safety and efficacy. Products must not be used concurrently with combustible tobacco product use, and e-cigarettes must not be used by non-smokers or by adolescents. Uncertainty exists on the long-term cardiovascular impacts, requiring further studies.

Conclusion

E-cigarettes pose a real but incompletely defined cardiovascular risk. They are not the safe alternative to combustible cigarettes that early marketing claimed. Experimental and clinical studies consistently link their use to autonomic imbalance, oxidative stress, endothelial dysfunction, and disrupted cardiac electrophysiology.

What this body of evidence shows, taken together, is a technology that changes the cardiovascular risk equation rather than removing it - trading one set of hazards for another rather than eliminating harm. The field still lacks the long-term data needed to size that risk precisely: most studies remain short-term, samples stay small, and device generations and e-liquid formulations vary too wide for clean comparison. No large prospective cohort has tracked e-cigarette users the way decades of research have tracked combustible smokers, so clinicians and regulators are left weighing a credible signal of harm without the hard endpoints to quantify it.

Clinicians should treat vaping as a genuine cardiovascular risk factor, not a benign habit, particularly in adolescents and young adults. Future research should prioritize longitudinal studies with standardized exposure measures and direct comparisons between exclusive e-cigarette use and dual use, to establish the dose-response data this scenario now demands.

Disclosure of conflict of interest

None.