# Heartburn

Heartburn is a burning sensation felt behind the breastbone. Heartburn, often linked to acid reflux, is often triggered by food, particularly fatty, sugary, spicy, chocolate, onions, citrus, and tomato-based products. Lying down, bending, lifting, and certain exercises can exacerbate heartburn. Causes of heartburn include acid reflux, non-acidic or weakly acidic reflux, damage to the esophageal lining, bile acid, mechanical stimulation to the esophagus, and esophageal hypersensitivity. Heartburn affects 25% of the American population every month.
Endoscopy and esophageal pH monitoring are used to evaluate heartburn. Some causes of heartburn, such as Gastroesophageal reflux disease (GERD) can be diagnosed based on symptoms alone. Potential differential diagnoses for heartburn include motility disorders, ulcers, inflammation of the esophagus, and medication side effects. Lifestyle changes, such as weight loss and avoiding fatty foods, can improve heartburn symptoms. Over-the-counter alginates or antacids can help with mild or intermittent heartburn. Heartburn treatment primarily involves antisecretory medications like H2-receptor antagonists and PPIs.

## Definition and symptoms

Heartburn is a burning feeling felt behind the breastbone, rising to the throat, and may be associated with an acidic taste. Heartburn is often associated with acid reflux or regurgitation. Heartburn is sometimes referred to as indigestion, sour stomach, acid regurgitation, or bitter belching. Heartburn is deemed troublesome if mild symptoms occur two or more days each week, or moderate/severe symptoms happen at least once per week.
Heartburn often spreads to the neck, throat, or back and is usually triggered by food. It tends to occur within an hour after eating, especially after a large meal. Fatty, sugary, and spicy foods, as well as chocolate, onions, citrus, and tomato-based products, can worsen heartburn.
Lying down, especially after eating late can make heartburn worse. Some people find it more severe when lying on their right side. Nighttime heartburn can disrupt sleep and affect daily life. Activities that increase abdominal pressure, like bending, lifting heavy objects, or certain exercises, can also trigger symptoms. Studies suggest that stress and lack of sleep may make heartburn feel worse by lowering the body's sensitivity to symptoms.

## Differential diagnoses

The differential diagnosis for heartburn includes motility disorders such as achalasia and gastroparesis, peptic ulcers, functional dyspepsia, angina, eosinophilic esophagitis, coronary artery disease, functional heartburn, peristalsis, acid reflux, inflammation of the esophagus, esophageal cancer, ischemic pain, hiatal hernia, biliary colic, inflammation of the stomach, inflammation of the gallbladder, stomach cancer, inflammation of the pancreas, gallstones, inflammation of the duodenum, pancreatic cancer, duodenal ulcer, and mesenteric adenitis. Heartburn can also be caused by certain medications such as nonsteroidal anti‐inflammatory drugs, corticosteroids, tetracycline antibiotics, bisphosphonates, calcium‐channel blockers, nitrates, tricyclic antidepressants, and anticholinergics.

## Pathophysiology

The exact causes of heartburn are not fully understood, but they likely involve multiple factors, including chemical irritation, pressure on the esophagus, and increased sensitivity to pain.
Acid reflux is an important cause of heartburn but isn't the only cause. A study in 1989 demonstrated this by giving participants acidic and basic solutions. The acidic solutions induced heartburn in all participants, however, the more basic solution still invoked heartburn in over 40% of the participants. Ambulatory pH monitoring reveals that just a small percentage of acid reflux episodes trigger heartburn.
Nerve endings and acid-sensitive ion channels in the deepest layer of the esophagus are usually protected by natural barriers. However, in GERD, one of the earliest signs of damage is the development of dilated intercellular spaces (DISs) in the esophageal lining. These spaces weaken the protective barrier, allowing acid and other substances to seep in. This triggers pain-sensitive nerves, sending signals to the brain and causing the sensation of heartburn.
Esophageal reflux can be classified as acidic (pH < 4), weakly acidic (pH 4–7), or non-acidic (pH > 7) using combined impedance/pH monitoring. Without PPIs, heartburn is mostly linked to acid reflux, but about 15% of cases involve weakly acidic reflux. Factors like high reflux reach, low pH, large pH drops, high reflux volume, and slow acid clearance increase the likelihood of symptoms. When taking PPIs twice daily, heartburn can still occur, with 17–37% of cases linked to non-acidic, usually weakly acidic, reflux.
Bile acid rising into the esophagus can cause heartburn, though it is slower and less intense than stomach acid exposure. This likely happens due to bile damaging cell membranes and releasing intracellular mediators. Studies monitoring acid and bile reflux together show that they often occur simultaneously.
Mechanical stimulation may play a role in heartburn. Esophageal balloon distension, especially in the upper esophagus, can trigger heartburn symptoms. This may be because the upper esophagus has more pressure-sensitive receptors than the lower esophagus. Acid exposure may also make these receptors more sensitive.
Esophageal hypersensitivity plays a major role in heartburn, especially in GERD patients with normal acid levels. As shown in balloon studies, these individuals are also more sensitive to mechanical pressure. The likely cause is altered brain processing (central sensitization) rather than issues with esophageal receptors. Anxiety and stress can further heighten heartburn perception, both through brain mechanisms and possibly by weakening the esophageal lining (dilated intercellular spaces).

## Diagnostic approach

Diagnostic investigations for the evaluation of heartburn include endoscopy and esophageal pH monitoring. GERD is commonly diagnosed based on symptoms of heartburn and/or regurgitation. Endoscopy may be used to evaluate people who don't respond to treatment for heartburn or those with alarm symptoms such as persistent vomiting, gastrointestinal bleeding, iron-deficiency anemia, involuntary weight loss, difficult/painful swallowing (dysphagia, odynophagia), epigastric mass, family history of esophageal or gastric cancer, and new onset of symptoms ≥50 years of age.
Endoscopy is the best test for detecting abnormalities in the esophageal lining like erosive esophagitis and Barrett's esophagus. Biopsies taken during the procedure can help assess for other conditions linked to heartburn, such as eosinophilic and lymphocytic esophagitis. The esophageal 24-hour pH test or the multichannel intraluminal impedance-pH test, is often performed in those with refractory heartburn who have undergone an endoscopy. High-resolution esophageal manometry (HREM) is the standard test for diagnosing esophageal motor disorders. It helps rule out major motility issues in patients with persistent heartburn who have normal endoscopy and pH testing. These disorders include achalasia, esophagogastric junction outflow obstruction, diffuse esophageal spasm, jackhammer esophagus, and absent contractility. HREM can also distinguish GERD from conditions like rumination and supra-gastric belching. In some cases, gastric scintigraphy may be used to detect gastroparesis.
Functional heartburn is a burning feeling behind the breastbone, similar to GERD, but without signs of acid reflux, esophageal motor disorders, or mucosal damage on diagnostic tests like reflux monitoring, manometry, or endoscopy. After tests have been performed to rule out other causes of heartburn, functional heartburn is diagnosed according to the Rome IV criteria:
* Burning sensation or pain behind the chest.
* Persistent symptoms despite effective acid-suppressing treatment.
* No signs of GERD or eosinophilic esophagitis as the cause of symptoms.
* No major esophageal motility disorders present.
To qualify as having a diagnosis of functional heartburn an individual must meet all diagnostic criteria for the past three months, with symptoms appearing at least twice a week and beginning at least six months before the diagnosis.

## Treatment

Lifestyle changes such as weight loss, and avoiding fatty, heavy, or spicy foods, particularly before bed, can improve symptoms. Over-the-counter alginates or antacids can be used on an as-needed basis to help with mild or intermittent heartburn. Individuals may aim to stop medications that can make heartburn worse. Physicians may prescribe PPIs for 4-weeks to treat heartburn. H.pylori, if found, can be treated. If someone doesn't respond to a PPI, physicians may try H2 receptor antagonists. As a person's symptoms improve, physicians may decrease the frequency or dose of medications.
Many drugs have been used to treat heartburn, but antisecretory medications like H2-receptor antagonists and PPIs have the most evidence for the treatment of heartburn. Low doses of tricyclic antidepressants and selective serotonin reuptake inhibitors may be used to manage functional heartburn.
Antacids are fast-acting, short-term remedies for heartburn, made from compounds like aluminium hydroxide, magnesium hydroxide, and calcium carbonate, which neutralize acid. They were commonly used before stronger acid-lowering drugs were discovered, mainly for occasional, post-meal heartburn or as needed. Alginate, extracted from seaweed and combined with sodium or potassium bicarbonate, is more effective than antacids for heartburn relief. In short-term GERD treatment (4 weeks), it works as well as PPIs. It is also used as an add-on therapy for patients with partial PPI response, improving heartburn control and quality of life more than PPIs alone. H2RAs help lower stomach acid by blocking histamine at specific receptors in the stomach lining. Their effect lasts between 4 and 8 hours, depending on the medication. They are mostly used for quick relief in people with mild acid reflux (GERD) or as an extra treatment alongside PPIs, especially at night since they are better at controlling nighttime acid levels.
PPIs reduce stomach acid by blocking an enzyme involved in its production, and their effects last much longer than H2RAs—around 16 to 18 hours. They are stronger and don't lose effectiveness over time. However, they don't work immediately and don't fix the root cause of acid reflux; they simply make the refluxed contents less acidic. P-CABs are a newer type of acid-reducing medication that work by blocking an enzyme involved in acid production. Vonoprazan is the most researched P-CAB and has been found to be just as effective as PPIs in healing esophagitis and preventing relapses. In more severe cases, it may work even better than PPIs. However, P-CABs have not been more effective than a placebo for treating symptoms in people with NERD, likely because this condition includes a mix of different underlying issues.
Prokinetics help clear stomach acid from the esophagus by improving muscle movement and speeding up stomach emptying, which can be slow in some GERD patients. Common prokinetics include metoclopramide, domperidone, mosapride, itopride, and prucalopride. Since GERD can be a motility issue, these drugs have the potential to address its root cause. However, there isn't strong proof that they effectively treat GERD. They are usually added to PPI treatment for patients whose heartburn doesn't improve with PPIs alone, but their effectiveness in this case is unclear. Baclofen is a GABA agonist that helps reduce reflux by decreasing the relaxations of the lower esophageal sphincter, which are a main cause of GERD. However, its use is very limited and is usually considered only as an add-on treatment for patients with persistent heartburn despite taking PPIs.

## Epidemiology

About 25% of people experience heartburn at least once a month, while 12% have it at least once a week. Clinically significant heartburn affects about 6% of the American population. Most people don't see heartburn as a serious medical issue and rarely seek medical help for it. A survey in Olmsted County, Minnesota, found that only 5.4% of people with heartburn had visited a doctor in the past year, even though their symptoms were moderately severe and had lasted for over five years.

## History

Heartburn was originally thought to be a feeling of intense emotion, linked to anger or distress. Shakespeare described heartburn in his play The Tragedy of Richard the Third as "A long-continues drudge and heart burning between the Queens kindred and the King's blood". Historical descriptions from the 1500s-1700s of heartburn include "a sharpness, soreness of the stomach, heartburning" and "a sharp gnawing pain at the orifice of the stomach". Throughout the 1500s-1800s, stonecrop, chewing green tea, and chalk or magnesia were used as remedies for heartburn.
Because the pain was felt in the chest and the focus was on the heart at the time, doctors initially believed heartburn came from the heart rather than the esophagus. This is why the terms "cardialgia" or "cardialgy" were first used to describe heartburn.
Throughout the 1700s-1800s, many different terms were used to describe acid reflux. An English dictionary from the mid-1700s defined cardialgia as "from cardia, the heart, or rather the left orifice of the stomach, and -algia, to be pained, the pain of the mouth of the stomach or heart-burn"".
Throughout history, the terms cardialgia, heartburn, pyrosis, dyspepsia, and indigestion were often used interchangeably and there was little advancement in differentiating the terms till the 1900s.

## Special populations
### Pregnancy

Heartburn is common in pregnancy, with an incidence ranging between 17% and 45%. Complications related to heartburn in pregnancy are rare, meaning that diagnostic tests such as upper endoscopy are usually not required, and the diagnosis is made based on symptoms.
Many different factors lead to the development of heartburn during pregnancy. Hormonal changes, such as higher levels of progesterone, relax smooth muscles, which lowers stomach tone and motility and reduces pressure in the lower esophageal sphincter. During pregnancy, the lower esophageal sphincter moves into the chest, where pressure is lower. This makes it easier for stomach acid and food to flow back into the esophagus, causing irritation and a burning sensation. Other factors that can cause heartburn during pregnancy include increased pressure on the stomach from the uterus, weight gain, changes in gastric emptying, delayed small bowel transit or medications.