Industrialization, urbanization, and globalization have led to increased exposure to different sources of noise including road traffic, aircraft, railway, industrial, and crowded neighborhoods.

Stress and annoyance caused by noise lead to endocrine and autonomic effects causing CVD including coronary artery disease (CAD), hypertension, heart failure, atrial fibrillation, and stroke. Noise exerts pathophysiologic effects related to the duration of exposure. Noise-induced stress increases blood pressure, blood sugar, cholesterol, and blood viscosity and can lead to oxidative stress with endothelial dysfunction and activation of prothrombotic and inflammatory pathways, triggering or worsening CVD.²

More than half the world’s population use solid fuel for cooking and heating. Sources include wood, crop residues, cow dung, and coal. Like fossil fuel combustion, solid fuel produces an amount of fine PM that exceeds the standards for outdoor concentration applied in the United States and European Union.

A study among rural Pakistani nonsmoking women demonstrated an independent significant association between the use of solid fuel and acute coronary syndromes.¹³ In rural China, almost 100,000 solid fuel users were followed for 7 years and found to have more CV and all-cause mortality than clean fuel (electricity, natural gas, and liquefied petroleum) users and those with appropriate ventilation.¹⁴ This was confirmed in a multinational study in more than 30,000 solid fuel users from middle- to low-income countries who experienced more fatal and nonfatal CV events (CHF, stroke, and MI) as compared to nonusers over a follow-up period of 9 years.¹⁵ Additional prospective studies on the acute and chronic CV response to household air pollution from solid fuel combustion are needed to better understand how the effects of this exposure differ from ambient air pollution.³

Aconite is derived from the plant Aconitum, which is ubiquitous in Europe, North America, and Asia and known by the common names of monkshood, wolfsbane, and “the devil’s helmet” (Figure 29.1). Aconite poisoning is more common in Asia where dried rootstocks of the Aconitum plants are used in Chinese herbal medicine (caowu, chuanwu, and fuzi). Toxicity may occur from ingestion following improper processing of the plant for use in complementary medicines, mistaking the plant for an edible species, and intentional suicide and homicide attempts. Aconite causes persistent activation of voltage-gated sodium and calcium channels, leading to sustained depolarization and resistance to excitation. It is toxic to the neurologic system (causing descending paresthesias, numbness, and mild weakness), gastrointestinal tract (inducing nausea, vomiting,
and diarrhea), and the CV system (causing malignant ventricular rhythms, hypotension, and shock).

Aconite poisoning is usually established clinically, but it can be confirmed with chromatographic and mass spectrometric analysis of serum and urine alkaloids and metabolites. The treatment of aconite poisoning is supportive.¹⁶ Because of the persistent activation of the voltage-gated sodium channels, class I antiarrhythmic agents (ie, sodium channel blocking agents) have been used to treat aconite-induced ventricular arrhythmias; additionally, high-dose magnesium sulfate therapy has been recommended based on in vitro and animal experiments as well as limited clinical case reports. When arrhythmias are resistant to pharmacologic therapy or direct cardioversion, mechanical support with cardiopulmonary extracorporeal bypass or a left ventricular assist device has been suggested as salvage therapy.

Cardenolides are naturally occurring cardiac glycosides found in plant species throughout the world. Their CV toxicity results from inhibition of the Na⁺/K⁺ ATPase channel. Accordingly, ingestion of cardenolides may lead to serious dysrhythmias, including second- or third-degree heart block, and cardiac arrest.

In South Asia, cardenolide poisoning from yellow (Thevetia peruviana), pink, or white oleander (Nerium oleander) (Figure 29.2) and fruits from the Cerbera manghas family (sea mango, pink-eyed cerbera, odollam tree, “suicide” tree) (Figure 29.3) is a leading cause of attempted suicide, with thousands of cases a year and a 5% to 10% case fatality ratio. Yellow oleander seed (or “codo de fraile”) is sold in some markets in Mexico and Central America, as well as on the Internet, as a “safe” and “natural” treatment for obesity.¹⁷ However, all parts of the plant are toxic no matter how it is prepared (fresh, dried, or boiled). Fatality may occur after ingestion of one leaf by children and in adults after eating 8 to 10 seeds, 15 to 20 g of the root, or 5 to 15 leaves. Accidental poisoning occurs in children who mistakenly consume the fruit—either in confusion for water chestnut or out of curiosity; and mixing the dried plant parts in herbal tea has resulted in accidental poisoning in adults.

Although the initial symptoms (headaches, intense abdominal pain, vomiting, diarrhea, and bradycardia) may show up within minutes after ingestion, prolonged hospitalization and observation are recommended after cardenolide ingestion, because the occurrence of dangerous dysrhythmias may be delayed up to 72 hours after ingestion. Patients who develop bradyarrhythmias may be medicated with atropine and isoprenaline or require a temporary pacemaker. A meta-analysis concluded that multiple doses of activated charcoal within 24 hours of toxin ingestion and administration of antidigoxin Fab antitoxin reduce the risk of cardiac dysrhythmias. Hemodialysis or hemoperfusion is ineffective in preventing toxicity because of the large volume of distribution of the toxin.

Grayanotoxin is a natural compound found in the leaves of various rhododendron species and in the honey derived from the nectar of these plants (so-called “mad honey”). The rhododendrons associated with mad honey are found in the Black Sea region of Eastern Turkey (where mad honey intoxication has been described most often) as well as in North America, Europe, and Asia. Mad honey has been used as a herbal medicine for the treatment of diabetes mellitus, gastrointestinal disorders, heart disease, hypertension, and sexual dysfunction; such usage has contributed to episodes of accidental poisoning.

Grayanotoxin binds with the voltage-dependent sodium channels in their active state, thereby preventing inactivation
(ie, the channels remain in a state of depolarization). This effect on the vagus nerve leads to increased parasympathetic tone, causing bradycardia, hypotension, and various degrees of atrioventricular block. Atrial fibrillation, asystole, and MI have also been observed following mad honey ingestion. In a review of ˜1200 cases of mad honey intoxication,¹⁸ the most common complaints were dizziness, nausea, and presyncope, and the electrocardiographic (ECG) findings were sinus bradycardia (80%), complete atrioventricular block (46%), atrioventricular block (31%), ST-segment elevation (23%), and nodal rhythm (11%).

The diagnosis of mad honey intoxication is usually based on the clinical history, but grayanotoxin levels from urine and blood of patients with mad honey intoxication—and in the honey consumed—can be measured with liquid chromatography/mass spectrometry for confirmation.¹⁹

The cardiac and general cholinergic symptoms of grayanotoxin poisoning generally occur within minutes to a few hours of mad honey ingestion and dissipate within 24 hours. If treatment is necessary, intravenous fluids, atropine sulfate, vasopressors, and temporary pacing all have been used successfully until the toxic effects of grayanotoxin resolve.²⁰

The areca (betel) nut is the seed of the areca palm (Areca catechu), which grows in much of the Tropical Pacific, Asia, and parts of East Africa; it is often chewed wrapped in betel leaves (Figure 29.4). Betel nut is the fourth most widely used addictive substance in the world—behind alcohol, nicotine, and caffeine—with betel nut chewers making up 10% of the world’s population (mostly in Asia and South Asia). Its users describe the stimulating symptoms of betel as similar to tobacco or cocaine, and it has also been used as a diuretic, laxative, and sexual stimulant. The active ingredients—arecoline, arecaidine, guvacine, and guvacoline—are alkaloids that produce parasympathetic effects as an agonist of nicotinic and muscarinic receptors.

Betel nut use can induce hypertension, sinus and supraventricular tachycardia, and acute MI. Compared to nonusers, individuals who chew betel nuts have a higher incidence of CV mortality, which may be attributable to the increased incidence of comorbidities (such as diabetes mellitus, hypertension, and obesity), contamination of trace heavy metals (such as arsenic and manganese), and periodontal disease, a known risk factor for CVD.

Although the majority of botanical products appear inherently safe, case reports have implicated several herbal supplements with cardiac toxicity risk (Table 29.2).²¹ Although case reports do not always demonstrate causation or association, reoccurrences raise concerns that the herbal supplements listed may be cardiotoxic for some individuals.

Camphor is a pleasant smelling terpene used in skin lotions and in many ayurvedic medicines intended for oral use as an abortifacient/contraceptive, analgesic, antipruritic, antiseptic, and aphrodisiac. Ingestion of 2 g of camphor is sufficient to produce toxic effects in adults. Initial symptoms may occur within 5 to 15 minutes of ingestion and include nausea and vomiting, oral and epigastric burning, a feeling of warmth, and headache. These symptoms may progress to altered mental status, convulsions, coma, and death, usually because of respiratory failure or neurologic complications. Clinical toxicity typically resolves within 24 hours in survivors.