Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Heartburn or pyrosis is a painful or burning sensation in the esophagus, just below the breastbone (sternum) caused by regurgitation of gastric acid. The pain often rises in the chest and may radiate to the neck, throat, or angle of the jaw. Heartburn is also identified as one of the causes of chronic cough, and may even mimic asthma. Heartburn main cause is gastroesophageal reflux disease, and it is a symptom of that disorder, but it can also be mistaken with other causes of chest pain, including life-threatening ones such as acute coronary syndromes.

Heartburn was first medically described by Blount in 1656, who called the symptom “Dyspepsy”.

There is no established system for the classification of heartburn.

The sensation of heartburn is caused by exposure of the lower esophagus to the acidic contents of the stomach. Normally, the lower esophageal sphincter (LES) separating the stomach from the esophagus is supposed to contract to prevent this situation. If the sphincter relaxes for any reason (as normally occurs during swallowing), stomach contents, mixed with gastric acid, can return into the esophagus. This return is also known as reflux, and may progress to gastroesophageal reflux disease (GERD) if it occurs frequently. If this is the case, the gastric acid and pepsin now located in the esophagus can injure the tight junction proteins in the esophageal epithelium. This results in increased paracellular permeability and dilated intercellular space and edema in the submucosa, which is amplified by an immunological mechanism mediated by inflammatory cytokines.

Heartburn is commonly caused by gastroesophageal reflux disease (GERD) or adverse reactions to various food and drugs, causing esophagitis. Life threatening causes of heartburn are far less common and include acute coronary syndromes and esophageal cancer. Very uncommon causes include CREST syndrome and Zollinger Ellison syndrome.

Heartburn must be differentiated from other diseases that cause chest pain, such as acute coronary syndromes.
Heartburn may also be differentiated from other diseases that cause dysphagia such as esophageal cancer, achalasia and eosinophilic esophagitis in high risk individuals.

Heartburn is a very prevalent symptom in general populations worldwide.

Common risk factors in the development of heartburn as a consequence of gastroesophageal reflux disease (GERD) are obesity, increasing age, smoking, hiatal hernia, white bread, chocolate, mint, cinnamon, carbonated beverages, fatty foods, alcohol, wine and beer.
Less common risk factors include certain genetic changes.

No screening is indicated for heartburn in asymptomatic patients.

Natural history of heartburn depends on its cause. The most common cause is gastroesophageal reflux disease (GERD) which, if left untreated, 20% of patients with GERD may progress to develop esophageal stricture due to excessive acid in the lower esophagus. Complications of GERD include:

• Barrett’s esophagus;
• Erosive esophagitis;
• Esophageal ulcer;
• Esophageal adenocarcinoma.

Prognosis of GERD is good with the appropriate treatment.

The diagnosis of heartburn is made based on the patient’s history. Diagnostic studies must be performed if patient is at high-risk for Barrett’s esophagus or if there are alarm signs. The diagnostic study of choice in such cases is upper endoscopy.

Heartburn per se is a symptom. It may be accompanied by other symptoms such as: regurgitation, and dysphagia. A positive history of nausea, vomiting, and regurgitation is suggestive of gastroesophageal reflux disease (GERD). Other symptoms of GERD include chest pain, cough, and odynophagia.

Patients with heartburn usually appear uncomfortable, but the symptoms are commonly mild and frequent. Occasionally the patients may appear ill due to the pain in a emergency department setting. Common physical examination may include hoarseness of voice, laryngitis, otitis media, and lung wheezes.

There are no laboratory findings associated with heartburn.

There are no ECG findings associated with heartburn.
The ECG may be useful in the diagnosis of cardiac causes of heartburn such as acute coronary syndromes.

There are no x-ray findings associated with heartburn.
X-ray may be used though, for differential diagnosis such as esophageal strictures or hiatal hernia.

There are no echocardiographic or ultrasonographic findings associated with heartburn as a symptom of gastroesophageal reflux disease (GERD).

There are no CT-Scan findings associated with heartburn.

There are no MRI findings associated with heartburn.

There are no other imaging findings associated with GERD. However, endoscopy may be used in screening for the complications associated with chronic GERD like barrett’s esophagus.

Other diagnostic finding present in heartburn and consistent with diagnosis of gastroesophageal reflux disease (GERD) is the presence of acidic reflux in the esophagus through the ambulatory reflux monitoring. The 12 lead ECG may be used if heartburn due to cardiac causes is suspected.

The treatment of heartburn in the setting of GERD is lifestyle modifications which include weight loss, elevating head of the bed and no eating before going sleep. The pharmacologic medical therapy is recommended among patients with persistent GERD despite following the lifestyle modifications. Antacids, histamine receptor antagonists, proton pump inhibitors, and prokinetics medications are used in treatment of GERD.

Surgery is not the first-line treatment option for patients with GERD. Surgery is usually reserved for patients with either chronic GERD, high volume of acid reflux, non-compliant medical therapy, the presence of large hiatal hernia, or with upper respiratory manifestations as hoarsness of voice and laryngitits. The nissen fundoplication is the operation of choice in patients with GERD.

Effective measures for the primary prevention of GERD include avoiding food that worsens the symptoms, smoking cessation, weight loss, eating frequent meals, and head raising of the bed while sleeping.

The primary and secondary prevention strategies for heartburn are the same.

The use of proton pump inhibitors for 8 weeks associated with lifestyle modifications is a cost-saving strategy in patients with heartburn and gastroesophageal reflux disease (GERD).

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Heartburn was first medically described by Blount in 1656, who called the symptom “Dyspepsy”.

• Heartburn was first medically described by Blount in 1656, who called the symptom “Dyspepsy”;^[1]
• The term heartburn was commonly used to describe the pain in the 16th century. It was believed that the pain originated in the heart, not the esophagus, and the first terms to describe the pain were cardalgia or cardialgy.
• In 1829, the Southey theorized that it could be caused by bile or acid;
• Pepsis is the latin name for digestion, hence, dyspepsia was the term used to describe “abnormal digestion”;
• Chalk, slop diets and charcoal had been used since the earliest times to provide symptomatic relief from dyspepsia, which was not associated with the stomach up to the 19th century;^[1]
• In the early 20th century the use of bland diets and milk ingestion was augmented by the addition of neutralizing compounds and antacids to control the symptoms of heartburn, though reports of side effects such as diarrhea and milk-alkali syndrome were common;
• In the 1970s the histamine –2 receptor antagonists became available for treating heartburn;
• In the 1980s the proton pump inhibitors became available for treating heartburn – dramatically improving the efficacy of the treatment.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

There is no established system for the classification of heartburn.

There is no established system for the classification of heartburn.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

The sensation of heartburn is caused by exposure of the lower esophagus to the acidic contents of the stomach. Normally, the lower esophageal sphincter (LES) separating the stomach from the esophagus is supposed to contract to prevent this situation. If the sphincter relaxes for any reason (as normally occurs during swallowing), stomach contents, mixed with gastric acid, can return into the esophagus. This return is also known as reflux, and may progress to gastroesophageal reflux disease (GERD) if it occurs frequently. If this is the case, the gastric acid and pepsin now located in the esophagus can injure the tight junction proteins in the esophageal epithelium. This results in increased paracellular permeability and dilated intercellular space and edema in the submucosa, which is amplified by an immunological mechanism mediated by inflammatory cytokines.^[1]

• Heartburn is the burning pain caused by the reflux of gastric acid and pepsin from the stomach into the esophagus.
• These substances enter the esophagus due to a dysfunctional lower esophagus sphincter, which in normal conditions should now allow the occurrence of such reflux.
• This can happen due to many causes such as hiatal hernia, use of medications which causes relaxation of the lower esophagus sphincter or due to abnormal relaxation or weakening of the lower esophagus sphincter which causes the gastroesophageal reflux disease.
• The gastric acid and the pepsin damages the epithelium and causes an inflammatory response mediated by IL-8 and IL-1B. These cytokines stimulate inflammation and sensitizes the peripheral nerves in the mucosa which mediates the pain. It is believed that the release of such cytokines is mediated by an increased production of PGE2 and ATP by the epithelium.^[1]

• With the most recent research findings, it is believed that the gastric acid does not directly cause heartburn, but causes it using a myriad of inflammatory mechanisms which are being elucidated and may be targets of new therapeutic drugs in the future.^[1]

• The esophagus is lined by nonkeratinizing, stratified squamous epithelium, and the stomach by columnar epithelium – in which every cell has a small surface area in contact with the organ lumen.
• The squamocolumnar junction is the point, where the epithelium lining the esophagus meets the epithelium lining the gastric mucosal folds.
• The gastroesophageal junction is the anatomic place where the esophagus meets the stomach and it is located at the same place as the squamocolumnar junction. *Patients with gastroesophageal reflux disease have a squamocolumnar junction which is moved proximally due to the changes occurring at the esophageal epithelium, which gradually changes into columnar epithelium, looking similarly as the gastric epithelium, and being located above the anatomical junction.^[1][2]

Many changes have been reported in the esophageal epithelium in patients with gastroesophageal reflux disease, as a response to damage. These changes have been summarized in the Esohisto project:

Histologic criteria for the recognition and assessment of microscopic lesions related to gastroesophageal reflux disease (GERD) – the Esohisto project criteria^[3]

Proliferative changes of the squamous epithelium	Criterion	Definition and method of assessment	Severity score
Basal cell layer Hyperplasia	Basal cell layer thickness in μm as a proportion (%) of total epithelial thickness (10×)	0 (<15%) 1 (15–30%) 2 (>30%)
Papillary Elongation	Papillary length in μm as a proportion (%) of total epithelial thickness (10×)	0 (<50%) 1 (50–75%) 2 (>75%)
Dilated intercellular spaces	Identify as irregular round dilations or diffuse widening of intercellular space (40×)	0 (absent) 1 (<1 lymphocyte) 2 (≥1 lymphocyte)
Inflammatory infiltrate	Intraepithelial Eosinophils	Count in the most affected high-power field (4×0)	0 (absent) 1 (1–2 cells) 2 (>2 cells)
Inflammatory infiltrate	Intraepithelial Neutrophils	Count in the most affected high-power field (40×)	0 (absent) 1 (1–2 cells) 2 (>2 cells)
Inflammatory infiltrate	Intraepithelial mononuclear cells	Count in the most affected high-power field (40×)	0 (0–9 cells) 1 (10–30 cells) 2 (>30 cells)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Heartburn is commonly caused by gastroesophageal reflux disease (GERD) or adverse reactions to various food and drugs, causing esophagitis. Life threatening causes of heartburn are far less common and include acute coronary syndromes and esophageal cancer.

These causes present with chest pain that may present similarly to heartburn and also other clinical features that occur with heartburn:

• Acute coronary syndrome
• Esophageal cancer
• Mediastinitis

• Gastroesophageal reflux disease (GERD)^[1]
• Esophagitis ^[2]
• Hiatal hernia^[3]
• Motility disorders (e.g., gastroparesis)
• Peptic ulcer disorder
• Lifestyle:
  • Exercise
  • Obesity
  • Smoking (tobacco)
  • Stress
  • Supine body position
  • tight-fitting clothing
• Medications:
  • Alpha-adrenergic antagonists
  • Anticholinergic agents
  • Aspirin and other nonsteroidal anti-inflammatory drugs
  • Beta2 -adrenergic drugs
  • Barbiturates
  • Benzodiazepines
  • Bisphosphonates
  • Calcium channel blockers
  • Chemotherapy
  • Dopamine
  • Estrogen
  • Iron
  • Narcotic analgesics
  • Nitrates
  • Potassium
  • Progesterone
  • Prostaglandins
  • Quinidine
  • Tetracycline
  • Theophylline
  • Tricyclic antidepressants
  • Zidovudine
• Dietary:
  • Alcohol
  • Caffeinated beverages
  • Carbonated beverages
  • Chocolate
  • Citrus fruit or juices
  • Fatty foods
  • Garlic or onions
  • Mint (peppermint, spearmint)
  • Salt and salt substitutes
  • Spicy foods
  • Tomatoes/tomato juice
• Other:
  • Genetics
  • Pregnancy^[4]

• Scleroderma
• Zollinger-Ellison syndrome
• Pericarditis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Heartburn must be differentiated from other diseases that cause chest pain, such as acute coronary syndromes.
Heartburn may also be differentiated from other diseases that cause dysphagia such as esophageal cancer, achalasia and eosinophilic esophagitis in high risk individuals.

• Heartburn must be differentiated from other diseases that cause chest pain, such as acute coronary syndromes.
  
• Heartburn may also be differentiated from other diseases that cause dysphagia in high risk individuals.
  
• Cardiac causes must be excluded since they can be life-threatening and may present with similar symptoms. In order to facilitate this, there’s a table below which describes the life-threatening causes which must be differentiated:

Differentiating heartburn from angina ^{[1] [2]}

Heartburn (GERD)	Angina or Heart Attack
Burning chest pain, begins at the breastbone	Tightness, pressure, squeezing, stabbing or dull pain, most often in the center
Pain that radiates towards the throat	Pain radiates to the shoulders, neck or arms
Sensation of food coming back to the mouth	Irregular or rapid heartbeat
Acid taste in the back of the throat	Cold sweat or clammy skin
Pain worsens when patient lie down or bend over	Lightheadedness, weakness, dizziness, nausea, indigestion or vomiting
Appears after large or spicy meal	Shortness of breath
	Symptoms appears with physical exertion or extreme stress

While evaluating heartburn and considering gastroesophageal reflux disease (GERD) its most probable diagnosis, there’s a diagnostic approach that must be performed in order to exclude other causes, especially in high risk patients, according the the American Journal of Gastroenterology guidelines^[3] :

Classic symptoms of GERD (heartburn and regurgitation)

If there are warning signs*: upper endoscopy during the initial evaluation

PPI 8-week trial

If better: GERD probable

If refractory, proceed to refractory GERD algorithm

• Dysphagia, bleeding, anemia, weight loss and recurrent vomiting are considered warning signs and should be investigated with upper endoscopy. Esophageal cancer, and other severe diseases including esophagitis may be considered, the latter especially in HIV patients.
  

Treat GERD: Start a 8-week course of PPI

If there are warning signs*: upper endoscopy during the initial evaluation

Refractory GERD

Optimize PPI therapy

No response: Exclude other etiologies

Typical symptoms: Upper endoscopy

Atypical symptoms: Referral to ENT, pulmonary, allergy specialist

Abnormal: (eosinophilic esophagitis, erosive esophagitis, other) Specific treatment

NORMAL

Abnormal: (ENT, pulmonary, or allergic disorder) Specific treatment

REFLUX MONITORING

Low pre test probability of GERD

High pre test probability of GERD

Test off medication with pH or impedance-pH

Test on medication with impedance-pH

• High Risk: Men >50 years with chronic gastroesophageal reflux disease symptoms (>5 years), AND:
  • Nocturnal reflux symptoms
  • Hiatal hernia
  • Elevated body mass index
  • Tobacco use
  • Intra-abdominal distribution of fat
• Heartburn must be differentiated from other diseases such as GERD, gastritis, peptic ulcer, crohn’s disease, gastric adenocarcinoma, and gastrinoma.^{[4][5][6][7][8][9][10][11][12]}

Differential Diagnosis

Disease

Cause

Symptoms

Diagnosis

Other findings

Pain

Nausea & Vomiting

Heartburn

Belching or Bloating

Weight loss

Loss of Appetite

Stools

Endoscopy findings

Location

Aggravating Factors

Alleviating Factors

GERD

Lower esophageal sphincter abnormalities Hiatal hernia Abnormal esophageal contractions Prolonged emptying of stomach Gastrinomas

Epigastric pain

Spicy food Tight fitting clothing

Antacids Head elevation during sleep

✔ (Suspect delayed gastric emptying)

✔

–

–

–

–

Esophagitis Barrette’s esophagus Strictures

Other symptoms: Dysphagia Regurgitation Nocturnal cough Hoarseness Complications Esophagitis Strictures Barrette esophagus

Acute gastritis

H. pylori NSAIDS Corticosteroids Alcohol Spicy food Viral infections Crohn’s disease Autoimmune diseases Bile reflux Cocaine use Breathing machine or ventilator Ingestion of corrosives

Epigastric pain

Food

Antacids

✔

✔

✔

–

✔

Black stools

Pangastritis or antral gastritis Erosive (Superficial, deep, hemorrhagic) Nonerosive (H. pylori)

–

Chronic gastritis

H. pylori Alcohol Medications Autoimmune diseases Chronic stress

Epigastric pain

Food

Antacids

✔

✔

✔

✔

✔

–

H. pylori gastritis Atrophy Intestinal metaplasia Lymphocytic gastritis Enlarged folds Aphthoid erosions

–

Atrophic gastritis

H. pylori Autoimmune disease

Epigastric pain

–

–

✔

–

✔

✔

–

H. pylori Mucosal atrophy Autoimmune Mucosal atrophy

Iron deficiency anemia Autoimmune gastritis diagnosis includes: Antiparietal and anti-IF antibodies Achlorhydria and hypergastrinemia Low serum cobalamine

Crohn’s disease

Autoimmune disease

Abdominal pain

–

–

–

–

–

✔

✔

Chronic diarrhea often bloody with pus or mucus Rectal bleeding

Mucosal nodularity with cobblestoning Multiple aphthous ulcers Linier or serpiginous ulcerations Thickened antral folds Antral narrowing Hypoperistalsis Duodenal strictures

Fever Fatigue Anemia (pernicious anemia)

Peptic ulcer disease

H. pylori Smoking Alcohol Radiation therapy Medications Zollinger-ellison syndrome

Epigastric pain sometimes extending to back Right upper quadrant pain

Duodenal ulcer Pain aggravates with empty stomach Gastric ulcer Pain aggravates with food

Antacids Duodenal ulcer Pain alleviates with food

✔

✔

–

–

–

Black stools

Gastric ulcers Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base Most ulcers are at the junction of fundus and antrum 0.5-2.5cm Duodenal ulcers Well-demarcated break in the mucosa that may extend into the muscularis propria of the duodenum Found in the first part of duodenum <1cm

Other diagnostic tests Serum gastrin levels Secretin stimulation test Biopsy

Gastrinoma

Associated with MEN type 1

Abdominal pain

–

–

✔ (suspect gastric outlet obstruction)

✔

–

–

–

Black stools

Useful in collecting the tissue for biopsy

May present with symptoms of GERD or peptic ulcer disease Associated with MEN type 1 Diagnostic tests Serum gastrin levels Somatostatin receptor scintigraphy CT and MRI

Gastric Adenocarcinoma

H. pylori infection Smoked and salted food

Abdominal pain

–

–

✔

✔

✔

✔

✔

Black stools, or blood in stools

Esophagogastroduodenoscopy Multiple biopsies are taken to establish the diagnosis

Other symptoms Dysphagia Early satiety Frequent burping

Primary gastric lymphoma

H. pylori infection

Abdominal pain Chest pain

–

–

–

–

–

✔

–

–

Useful in collecting the tissue for biopsy

Other symptoms Painless swollen lymph nodes in neck and armpit Night sweats Fatigue Fever Cough or trouble breathing

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Heartburn is a very prevalent symptom in general populations worldwide.

• In 2013, the prevalence of gastroesophageal reflux disease (GERD) was estimated to be:
  • 18,100–27,800 cases per 100,000 individuals in North America,
  • 8,800–25,900 cases per 100,000 individuals in Europe,
  • 2,500–7,800 cases per 100,000 individuals in East Asia,
  • 8,700–33,100 cases per 100,000 individuals in the Middle East,
  • 11,600 cases per 100,000 individuals in Australia,
  • 23,000 cases per 100,000 individuals in South America.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Common risk factors in the development of heartburn as a consequence of gastroesophageal reflux disease (GERD) are obesity, increasing age, smoking, hiatal hernia, white bread, chocolate, mint, cinnamon, carbonated beverages, fatty foods, alcohol, wine and beer.
Less common risk factors include certain genetic changes.

• Common risk factors in the development of heartburn as a consequence of gastroesophageal reflux disease (GERD) are obesity, increasing age, smoking, hiatal hernia, white bread, chocolate, mint, cinnamon, carbonated beverages, fatty foods, alcohol, wine and beer.
• Exercising and coffee intake were considered protective factors.^[1]
• Women experience heartburn generally 5 years later than men.^[2]

List of risk factors for heartburn^[3][1]

Risk Factors:
Obesity
Age
Smoking
Hiatal Hernia
Dietary Risk Factors
White bread
Chocolate
Mint
Cinnamon
Carbonated beverages
Fatty foods
Alcohol – Wine and ber
Genetic Risk Factors
C allele in FOX1 rs9936833 – ↑ reflux symptoms
A allele in MHC rs9257809 – ↑ reflux symptoms
rs10419226 (chr 19) – ↑GERD symptoms
rs2687201 (chr 3) ↑GERD symptoms
ABHD10, RNF7, RASGRF2, BTF3P7, C8orf4, GLDC, and ADAMTS17

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

No screening is indicated for heartburn in asymptomatic patients.

No screening is indicated for heartburn in asymptomatic patients.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2] José Eduardo Riceto Loyola Junior, M.D.[3]

the natural history of heartburn depends on its cause. The most common cause is gastroesophageal reflux disease (GERD) which, if left untreated, 20% of patients with GERD may progress to develop esophageal stricture due to excessive acid in the lower esophagus. Complications of GERD include:

• Barrett’s esophagus;
• Erosive esophagitis;
• Esophageal ulcer;
• Esophageal adenocarcinoma.

Prognosis of GERD is good with the appropriate treatment.

• The natural history of heartburn depends on the cause. The most common cause of heartburn is GERD but there are many other causes with different progressions.
• The symptoms of GERD include heart burn, regurgitation, and dysphagia. Other causes such as acute coronary syndromes may have a type of chest pain that is described similarly to heartburn but radiates to the left shoulder or neck and that is worsened by exercise.
• If left untreated, GERD will develop to esophageal stricture which occurs in around 20% of the patients with GERD.^[1]
• Esophageal stricture occur due to excessive acid in the lower of the esophagus which lead to scar formation. This scar causes narrowing of the esophagus and may lead to difficulties in swallowing.
• Acute coronary syndromes are life-threatening conditions due to acute coronary blood flow obstruction that may present with unstable angina, NSTEMI or STEMI.
• Scleroderma is a slowly progressing disease without a disease-modifying treatment that may present with progressive heartburn, dysphagia and symptoms present in the CREST syndrome.
• Esophageal cancer is usually of adenocarcinoma type that presents very aggressively and with a poor prognosis in most cases.

Complications that can develop as a result of GERD include the following:^[2]

• Barrett’s esophagus:
  • A type of dysplasia, is a precursor high-grade dysplasia, which is in turn a precursor condition for carcinoma. The risk of progression from Barrett’s to dysplasia is uncertain but is estimated to include 0.1% to 0.5% of cases, and has probably been exaggerated in the past.
  • Due to the risk of chronic heart burn progressing to Barrett’s esophagus, EGD every 5 years is recommended for patients with chronic heartburn, or who take drugs for chronic GERD.
• Erosive esophagitis
• Esophageal ulcer:
  • The excess acid secretion in the esophagus can lead to ulcer formation which increases pain in GERD patients.
• Esophageal adenocarcinoma
• Acute coronary syndromes may lead to death, heart failure, arrhythmias or mechanical complications.

• The majority of patients with GERD respond to nonsurgical measures, with lifestyle changes and medications. However, many patients need to continue to take drugs to control their symptoms.
• Prognosis of heartburn as a symptom of other diseases is more variable.
• Scleroderma is a progressive disease with poor prognosis.^[3]
• Acute coronary syndromes are life-threatening conditions that can present with variable prognosis when properly treated. Prognosis tend to be poor and may lead to death or severe heart failure if not treated.Harjola, Veli‐Pekka, et al. “Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high‐risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology.” European Journal of Heart Failure (2020).