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Entry

Understanding the Gut-Heart Axis in Roemheld Syndrome: Mechanisms and Clinical Insights

by
Bryan J. Mathis
1,*,
Ryuji Suzuki
2,
Yukihito Kuroda
3,4,
Hideyuki Kato
1 and
Yuji Hiramatsu
1
1
Department of Cardiovascular Surgery, Institute of Medicine, University of Tsukuba, Tsukuba 300-2635, Japan
2
Tsukuba Gastrointestinal Hospital, Tsukuba 300-1252, Japan
3
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba 300-2635, Japan
4
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10027, USA
*
Author to whom correspondence should be addressed.
Encyclopedia 2024, 4(4), 1721-1738; https://doi.org/10.3390/encyclopedia4040113
Submission received: 1 October 2024 / Revised: 14 November 2024 / Accepted: 18 November 2024 / Published: 21 November 2024
(This article belongs to the Section Medicine & Pharmacology)
Browse Figures
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Definition

:
This entry reviews the health condition known as Roemheld syndrome, or gastrocardiac syndrome in modern medicine. A pathology of gastrointestinal origin, the syndrome relies on a gut–brain–heart triad, interconnected by the vagus nerve. Pressure from the intestines pushes the stomach into the diaphragm and activates the vagus nerve, which affects the heart rate and gives the perception of cardiac issues. This distressing sensation, which usually comes after meals or with other digestive problems, causes anxiety or panic. Although events not arising from anatomic abnormalities are relatively harmless, hypersensitivity to these uncomfortable sensations may precipitate psychiatric problems (anxiety or depression) that cause repeated gastrocardiac events through sympathetic activation and the disruption of peristalsis. Treatment is usually symptomatic and may include diet, lifestyle changes, probiotics, or prescriptions that increase gut motility, but this specific set of reproducible symptoms may also be caused by hiatal hernia or side effects from medication/surgery and treated with respect to those mechanical causes. This review highlights details from the most current knowledge of the condition and offers suggestions for clinical management based on the literature.

1. Introduction

Roemheld Syndrome, first reported in the early 20th century by Austrian physician Ludwig von Roemheld, is usually seen in overweight, middle-aged males and was described as a set of symptoms that center around the digestive system and its proximity to the heart. These men would complain of shortness of breath, fatigue, anxiety, and vertigo while displaying cardiac-focused symptoms such as palpitations, angina pectoris, bradycardia, or sometimes tachycardia. Dr. Roemheld, even with the more primitive medicine available in his time, was almost certain that none of these patients had any true cardiac problems since the episodic symptoms only manifested soon after meals. In the ensuing 100+ years, the interconnected symptoms between heart and stomach were not seen as a comprehensive pathology, although older reports noted the practices of cardiology and gastroenterology were often related in patients complaining of both cardiac and digestive issues [1]. In modern medicine, this set of specific symptoms has evolved into the term “gastrocardiac syndrome” (hereafter GCS) and is usually treated symptomatically unless anatomic correction by surgery is possible.
Clinically, only scarce case reports exist, and no large-scale studies or exploratory literature have been published on this topic. Only recently has a connection between GCS and the autonomic nervous system been revisited. As the longest cranial nerve that connects both heart and viscera, the vagus nerve has been found to play a central mediation role between digestion and heart rate braking functions. Here, the GCS Triad (gastrointestinal system, heart, psychiatric issues, all interconnected by the vagus nerve) is detailed and dissected from an anatomical view to reveal likely causes for symptoms and comorbidities that it may exacerbate, along with suggestions for treatment.

1.1. Literature Search Strategy

As two names exist for this condition, the keywords “Roemheld syndrome” and “gastrocardiac syndrome” were used to search for the associated literature (reviews, case reports, etc.) in PubMed/Medline. The literature that included cardiac effects mediated by gastrointestinal pathologies were included, as were reports of the effect of the vagus nerve on both systems. Since the term “gastrocardiac” is sometimes used to describe a cardiac-adjacent location for ulcers within the stomach, these reports were excluded, as the ulcer may rarely erode into the heart myocardium, necessitating repair, and this outcome is not reliant on the GCS Triad.

1.2. Medical Case History and Prevalence

In healthy people, GCS is most likely upsetting but essentially harmless as the symptoms disappear over time; however, in patients with other pathologies, GCS may be an important indicator of digestive system issues. In 2020, Mehta and colleagues encountered a representative case of a 62-year-old woman who experienced distressing heart palpitations of a moderate, fluttering, and non-radiating nature that were accompanied by mild vertigo, sweating, and shortness of breath [1]. No angina, syncope, or other severe issues were noted, but the timing always came after meals (lunch and dinner). After noting a medical history of GERD, obesity, and hiatal hernia, testing revealed over 35,000 ectopic beats per day (14.6% burden) but with a normal ejection fraction and no signs of ischemic heart disease or other cardiovascular disorders. She was then found to have a 5 cm hiatal hernia that was surgically corrected, resolving the symptoms (ectopic burden of 0.1%).
These findings are similarly reported in several other case studies that involve older, adult patients with hiatal hernias; esophageal pathologies (e.g., GERD/Barrett’s esophagus); or gastric distention/excessive flatus [2,3,4]. Thus, a picture emerges of a reproducible set of symptoms that reliably erupt when gastrointestinal pressure impinges into the thoracic cavity from the diaphragm side or affects the nerves that pass through it, especially the vagus nerve. Once these underlying issues are addressed, the cardiac symptoms are rapidly resolved. A summary of currently published cases is available in Table 1.
No current reports detail the prevalence within any population, adult or pediatric; the literature searches reveal only sparse case literature. Thus, standardized diagnostic and treatment criteria remain unestablished and treatment is based on individual symptoms.

1.3. The Vagus Nerve: One Nerve to Rule Them All

Named for its wandering nature, cranial nerve X starts within the medulla oblongata and terminates within the small intestine, with large branches in the cardiac, pulmonary, and gastrointestinal systems. Bidirectional data flow allows for the precise parasympathetic nervous system (PNS) regulation of respiration; oxygenation; smooth muscle contractility (e.g., variable heart rate, elastic vessel tone, and rhythmic peristalsis); digestion (bile release, acid secretion, etc.); and autonomic nervous system switching (i.e., parasympathetic activation to regulate the sympathetic innervation from the spine). It is the primary and direct connection of the brain to parasympathetic regulation of the cardiopulmonary and digestive organs and also supplies innervation to the muscles that control speech near the thyroid gland and in the tongue (intrinsic larynx muscles and palatoglossus muscle) [5]. Of concern are the branches (left and right) within the cardiovascular and gastrointestinal systems, since the vagus may transduce signals from the gut to the heart. GCS, as a discrete pathology involving both systems, relies on communication between the gut and heart through the vagus nerve to generate its specific symptoms.
In the context of the GCS Triad, the vagus nerve is of primary importance as it is the braking system of the heart rate (heart-rate variability control) and also modulates the sensing of inflammation, as well as the deployment of anti-inflammatory responses via the cholinergic anti-inflammatory pathway [10]. The vagus nerve affects all parameters of heart function, as evidenced in a trial of chronic heart failure patients who received cervical vagus nerve stimulator implants in the ANTHEM-HF trial; these patients, regardless of right or left vagal location, experienced increased left ventricular ejection fraction, left ventricular end-systolic volume, and left ventricular end-systolic diameter, along with significantly improved heart rate variability and exercise stamina [11]. Heart rate and blood pressure were also shown to be affected in the INOVATE-HF and NECTAR-HF vagus stimulation implant trials, as sympathetic control of the heart (higher blood pressure, faster pulse, lowered fibrillation threshold) is countered by the boosted parasympathetic tone [12]. Thus, the vagus nerve is a critical mediator of the GCS Triad, as it may itself regulate the action of the heart, as well as transduce errant signals from the digestive organs to the heart.

1.4. The Gut as the Birthplace of GCS

The gastrointestinal system, which involves multiple organs (including the liver and pancreas), consumes up to 10% of total daily energy expenditure to assimilate nutrients and is heavily innervated by the PNS, especially the vagus nerve [13]. Separated from the thoracic cavity by the diaphragm, the abdominal cavity is heavily muscled on all sides to provide contractile action (through sympathetic nervous system [SNS] signals from the T7-T12 intercostal nerves) for defecation and vomiting, plus sneezing and coughing in concert with the diaphragm [14]. The stomach itself is controlled by the vagus (PNS); pelvic splanchnic (SNS, from the spine); and paraaortic autonomic plexuses, in addition to multiple other control centers (Figure 1). The vagus nerve also adds central control over bile release, plus acid and gastrin release through thyrotropin-releasing hormone from the medulla that transduce through the vagus via M3 cholinergic receptors and histamine [15]. Fine control of intestinal digestion and peristalsis is then provided through the parasympathetic nervous system, under control of the vagus nerve, and the myenteric/submucosal plexuses (Auerbach’s and Meissner’s plexuses) that function as a wrapped layer around the lumen to innervate the muscularis interna layer with spike-wave signals that create pulsatile contractions to move food, chyme, and other liquids unidirectionally through the gut [16]. Of note, Meissner’s plexus is primarily associated with PNS, while Auerbach’s plexus can transduce both PNS and SNS signals. Interstitial cells of Cajal in Auerbach’s plexus provide a pacemaker effect, controlling the duration and period of the contractile pulses. Biochemically, mechanical distention of the gut lumen as a bolus is passed releases 5-HT from enterochromaffin cells (synthesized from tryptophan) that is crucial for propagating peristalsis [17].
It is defects in this peristaltic system, usually considered as part of the irritable bowel syndrome (IBS) pathology, that are causative for GCS through aberrant or absent nerve signals from distension, pathologies, or infection. Essentially, pressure from the gut forces the diaphragm up, impinging into the thoracic cavity and pressing on the efferent branches of the vagus nerve, causing a negative chronotropic/dromotropic burst of parasympathetic vagal “static” that may also briefly lower thresholds for atrial fibrillation switching and reduce contractility [18]. Mechanical irritation of the atria or chemical burn-induced remodeling of the esophagus due to reflux disease may also synergistically contribute to atrial fibrillation [19]. It is this phenomenon that causes the symptoms felt and reported by GCS patients in the case literature; these symptoms disappear when the underlying gastrointestinal pathology is resolved. Thus, the “gut brain”, a term describing the collective action of the over 160 million neurons in the gastrointestinal tract that are coordinated by spinal/vagal nerve interplay, maintains a key role in GCS and modulation of GI neuronal activity and the peristalsis it controls may therefore be a key component of preventing or treating GCS in a clinical setting [20].

1.5. Modulating the Gut Brain

Outside of the brain, the gastrointestinal system is the largest concentration of neurons in the human body, and each must act in concert to keep secretion, primary/secondary peristalsis, and segmentation intact while food, gas, and liquid unidirectionally transit the digestive tract.
Of note, the digestive system is tied into CNS external threat perception directly through spinal nerves which can allow SNS activation by simply suppressing activation of the PNS. Once activated through SNS action, hormonal messengers, such as adrenaline/cortisol can suppress peristalsis, shunting blood elsewhere during the fight/flight/freeze response. Conditions that reduce or alter the level of 5-HT (such as selective serotonin reuptake inhibitors, or stress) may also ablate or stimulate peristalsis; both are considered a key element in the pathogenesis of the IBS family of symptoms (diarrhea, constipation, etc.) that can exacerbate GCS. The gut flora has also been shown to modulate enteric neurotransmitters (i.e., GABA, acetylcholine) and, as such, dysbiosis is considered a key driver of GCS [21].
The “rest and digest” function of the PNS is balanced in the gut by the SNS, which maintains peristalsis and the heart rate necessary to suffuse digestive organs with blood. Thus, PNS/SNS activation is not a binary state switching but rather a carefully controlled, analog condition with predetermined thresholds of activation to maintain rhythmic and unidirectional motion; secrete acid, gastrin, and bile; and sense nutrition in chyme. For this reason, stress perceived by the brain is transmitted through the autonomic nervous system to prepare for fight or flight by suppressing vagal action and permitting the SNS to take over. This fast-stress response activates the sympathetic–adreno–medullar axis and catecholamines (adrenaline, norepinephrine), plus cortisol, to suppress peristalsis and shunt blood to extremities while increasing respiration and heart rate. The freeze response, conversely, is mediated by the PNS when fight or flight is impossible (“terror” situations) and the body prepares to ablate the damage from danger by vagal domination and subsequent slowing of heart rate, blood pressure, and respiration to lessen the effects of bleeding [22]. The freeze effect may result in syncope or dizziness due to hypotension, but usually creates a reduction in mobility to reduce fast motion that is theorized to reduce predator threats (“playing dead”) or give time to synthesize a threat response [23]. This response is dominated by acetylcholine, which may cause spontaneous vomiting or defecation through enhanced activation of muscarinic acetylcholine receptors in the intestines, but also features the hypothalamus-pituitary-adrenal (HPA) axis release of corticotrophin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) [24]. These two hormones have been found as key modulators of intestinal motility and excess CRH was reported to induce duodenal dysmotility in IBS patients [25]. Thus, acute stress states that lead to partial activation of any preprogrammed fear state (fight/flight/freeze) can severely disrupt the activity of the gut brain and peristalsis by increasing hormones that act on the autonomic nervous system (ANS), which controls both systemic stress response and digestion.
Recently, the chronic state of stress (as opposed to acute stress) has come into focus as a chief regulator of GI issues in the modern world since low-level but constant stress states keep a small amount of both SNS-activating hormones in the bloodstream at all times. Acute stress/anxiety has also been shown to downregulate activation of the α7-nicotinic acetylcholine receptors which are abundant in the intestines to regulate secretion of glucagon-like peptide-1 from L cells and downregulate cytokine-based inflammation that interferes with peristalsis [26,27]; anxious rats treated with vagal nerve simulation (increasing nicotinic receptor activity) experience reduced stress symptoms as well as restoration of intestinal function from stress-induced IBS [27]. Of importance, vagal nerve stimulation has the double effect of restoring normal digestion and reducing anxiety/panic by checking sympathetic activation, as well as reducing inflammation that might irritate digestive tissues [28]. Thus, the vagus nerve is a critical interface that transduces anxiety and panic from the brain to the gut and heart, but may also transmit errant signals that cause symptoms which sensitize the brain to anxiety/panic with regard to signals from IBS; this is the result of bidirectional signaling.
A state of chronic, low-level sympathetic activation (e.g., anxiety disorders) may dysregulate the vagal control of the digestive system through loss of tone, especially in anxiety/panic sufferers, and disrupt peristalsis, acetylcholinergic receptor function, acid/enzyme secretion, and anti-inflammatory activities. These collective GI symptoms from chronic stress and/or anxiety are termed irritable bowel syndrome (IBS) and 11% of the world suffers from some form of it [29]. To compare, a meta-review estimated that 39% of people with IBS also suffer from anxiety disorder; the effect of anxiety, as reflected in a loss of vagal tone and subsequent sympathetic overactivation, is therefore both a key driver and result of GCS [30]. In this syndrome, intimately related to GCS, cortisol from long-term stress can disrupt peristalsis, while ACTH and CRH promote dysmotility in the small intestine and disruptions in the migrating motor complex can push colonic flora into the small intestine, creating small intestinal bacterial overgrowth (SIBO) and large volumes of gut-distending gas that exert pressure on the vagus nerve and promote GCS episodes. As gut flora modulate gut serotonin with short-chain fatty acids and also produce ACTH/galanin-mediated cortisol release, dysbiosis can also become a chief driver of IBS symptoms, and the effect of these symptoms may increase perceived chronic stress that further disrupts the digestive system in a positive feedback loop [31]. Disruptions in ANS balance may also create conditions of excessive or insufficient acid release in the stomach, plus secretory irregularities in bile and pancreatic enzymes (bicarbonate, pancrease). Combined with dysmotility (from any source, but primarily stress), IBS symptoms may also reduce digestion efficiency, create chronic diarrhea or constipation, and errantly stimulate the vagus nerve to propagate cardiovascular symptoms of GCS. Constipation-dominant IBS (IBS-C), in particular, has been linked to GCS in popular media, due to the presence of increased methanogenic bacteria that slow peristalsis [32].
An ideal digestive system would have its own nervous system that was insensitive to stress hormones used for survival, but the economy of evolution selected for digestive systems that could be controlled by nervous branches responsive to stress as an adaptation to provide extra blood to perfuse muscles and increase physical capabilities in the face of acute danger. As the modern world is, essentially, far safer than the wild nature our ancestors roamed, most of the stress humans face is chronic and low-level, exploiting that very specific flaw to disrupt the gut brain and create a unique environment to promote GCS through psychiatric and IBS symptoms, especially IBS-C, transduced through the vagus nerve. Thus, the GCS Triad is established and reinforced.

1.6. Special Case: Hiatal Hernia Pathology as Causative for GCS

Hiatal hernias occur when the upper section of the stomach (fundus, cardia, upper body) infiltrate into the thoracic cavity via a weakened esophageal hiatus, impinging into the lungs and relaxing the abdominal section of the esophagus, forcing open the lower esophageal sphincter. Typical hiatal hernias present with gastroesophageal reflux (GERD, especially when prone), pain, dysphagia, and feelings of fullness. Severe cases of extended reflux may also cause Barrett’s esophagus as a complicating factor. Laparoscopic surgery is usually corrective, with GI symptoms resolving soon after correction, but osteopathic manipulation in lieu of surgery was also reported to resolve a hiatal hernia in a 71-year-old female [33].
The increased intrathoracic pressure resulting from a hiatal hernia may also stimulate GCS symptoms, such as tachycardia, premature ventricular contractions, atrial fibrillation, or other arrythmias, through anterior vagal nerve stimulation, as seen in several reported cases [4,5,33]. The literature indicates that hiatal hernias are a risk factor for cardiac arrythmias, with a 2013 study by Roy and colleagues indicating a 17.5-fold (men) or 19-fold (women) increase in atrial fibrillation occurrence in populations with hiatal hernias [34]. A review by Goodwin and colleagues also points to pulmonary compression and increased pressure on the left atrium as potential causes for atrial fibrillation in hiatal hernia cases [35]. Thus, GCS symptoms in populations at risk for hiatal hernias (usually over 50 years of age, male, and obese) may point to the need for GI screening in order to simultaneously resolve both the primary hernia and GCS through surgical repair [36].

1.7. The Heart as the GCS Victim: A Fear-Amplification System

The most distressing and recurring symptoms of GCS are centered around the heart. As with all rhythmic, contractile tissues, myocardial contractility is precisely regulated by a dedicated electrical system centered in the sinoatrial node (SAN) that sends a propagating electrical wave across the heart that starts in the atria and is then conducted by His-Purkinje bundles (right and left) to the ventricles [8]. The four chambers of the heart thus fill and contract in a specific sequence (right atrium to right ventricle to the lungs via the pulmonary artery then back to the left atrium, the left ventricle and out to systemic circulation). This sequence is tightly controlled by the SAN, which itself is innervated by PNS ganglia originating in the right vagus nerve trunk. These PNS ganglia are situated around the left atrium, also infiltrating into the ventricular myocardium, and serve as a brake (via acetylcholine release) to slow heart rate, reduce atrioventricular conduction, and lower ventricular contractility without affecting the rhythmic pulses of the SAN [18]. The PNS system therefore specifically serves to generate negative chronotropic/dromotropic effects via the SAN (and alterations in conduction within the atrioventricular node), alter atrial fibrillation thresholds, create a negative ionotropic signal on the ventricular myocardium, reduce ventricular arrythmia thresholds, prevent SNS-activated heart rate increases, open up the coronary artery during exercise (via nitrous oxide release), and also maintain baroreflexive responses within the coronary artery [18,37,38,39]. As the vagus nerve is directly connected to the SAN, errant signals traveling up from the gut can activate the vagal braking system and cause the SAN to slow the heart rate; other parts of the heart conducting the previous signal may thus transduce an ectopic beat, causing palpitations that are the most common symptom of GCS [40]. As such, anything which may affect vagal signal fidelity or transmission could also affect the heart rate via these anatomic mechanisms.
The effect of anxiety/panic response may further complicate returns to cardiac homeostasis during GCS attacks as the same chronic stress response that affects the GI tract also directly acts on the cardiovascular system. Adrenaline and norepinephrine, released during anxiety, elevate systolic blood pressure, heart rate, and temporarily overcome vagal control. In addition, palpitations and variations in heart rate are common symptoms of anxiety and panic attacks. Cortisol, released under chronic stress/anxiety, increases T1 time, inducing reductions in heart rate variability (HRV) and also causing LV hypertrophy (and compensation that may further affect HRV) over long periods of exposure [41]. Conflicting signals (i.e., biochemical from adrenaline simultaneously with errant vagal activation from GCS) may therefore cause the cardiac irregularities seen in case reports and panic over perceptions of suffering cardiac arrest can sustain adrenaline/norepinephrine release for hours, overwhelming vagal control.
Repeated episodes cause enhancement of amygdala sensitivity and lower subsequent thresholds of panic activation through norepinephrine’s effect on the memory enhancing β-adrenergic receptors in the vagus nerve that then directly stimulate noradrenergic neurons in the locus coruleus [24]. This positive-feedback loop means that future GCS episodes may more easily trigger catecholamine release and the panic response since hypersensitivity in vagal afferents ablates the medulla’s ability to gate signals that cause amygdala activation and subsequent release of norepinephrine [24]. Over time, this repeated stimulation results in overactivation of the HPA axis; enhanced nociception or interoception (that may trigger fear responses, especially if pain or odd sensations are felt in the thoracic area); and hypervigilance that may resemble chronic stress with regard to somatic conditioning. Essentially, repeated GCS episodes may enhance SNS dominance, further exacerbating both IBS and anxiety/panic responses, which are then able to sustain a gut–vagus–cardiac mechanism that self-propagates through chronic stress-induced disruptions in digestion that create mechanical distention which generates vagal static. In turn, this signal propagates GCS cardiac-focused symptoms (such as palpitations) that exploit a hypersensitive amygdala which then dumps catecholamines that both maintain the loss of cardiac homeostasis, as well as lowering thresholds for the next gut-induced GCS activation [42]. In this manner, fear is amplified and ingrained into the nervous system via a positive-feedback system.

1.8. Cardiovascular Reflexes and GCS

The heart has a set of reflexes that serve to maintain blood pressure, rhythmic, and functional homeostasis. These reflexes are carefully regulated feedback loops designed to coordinate with the vagus nerve and are conserved in all mammals. Therefore, disruptions transduced through the vagus nerve due to IBS pressure in the thoracic cavity or via the vagus nerve may cause GCS symptoms through manipulation of these reflexes. In humans, there are five such reflexes tied to both GCS and vagally mediated homeostasis: the baroreceptor, chemoreceptor, Bainbridge, Bezoid-Jarisch, and Valsava. Each reflex, by common ties to the vagus nerve, may have ties to GCS and contribute to the symptoms experienced during an exacerbation.

1.8.1. The Baroreceptor Reflex

The baroreceptor reflex is a negative feedback loop that maintains higher arterial pressure in the carotid sinuses and aortic arch while lowering relative pressure in the atria, pulmonary system, and ventricles. This reflex is regulated by large, myelinated type-A vagal fibers that control pressure and heart rate second-to-second (variability) while smaller, unmyelinated type-C vagal fibers modulate tone and basal blood pressure [33]. In this reflex circuit, the carotid sinus nerve communicates directly with the vagal trunk (PNS) and cervical ganglion (SNS), and the sinus itself responds to acetylcholine. As the atrial/medullar link is through the vagus nerve, modulation of angiotensin, aldosterone, and vasopressin are affected by the PNS [43]. Thus, vagal static from GCS may cause changes in blood pressure or temporarily shift blood pressure balance via the baroreceptor reflex. This could result in the dizziness or other effects experienced during a GCS episode.

1.8.2. The Chemoreceptor Reflex

The chemoreceptor reflex specifically responds to hypoxic and hypercapnic conditions in the carotid sinus or brainstem, respectively. The carotid chemoreceptors are sensitive to oxygen, carbon dioxide, and blood pH affected by bicarbonate ions, similar to the brainstem sensors since the blood–brain barrier facilitates bicarbonate ingress [44]. Low oxygen/high carbon dioxide conditions activate the SNS through these dual receptor beds and increases breathing rate, also stimulating heart rate [45]. However, panic induced by feelings of heart-focused symptoms during GCS may drop carbon dioxide levels below homeostasis via hyperventilation, inducing an alkalotic state through reduced carbonic acid in the blood [46]. This pH shift causes a compensatory decrease in bicarbonate via lower kidney reabsorption and loss of potassium; symptoms are tingling extremities, tremors, weakness in the skeletal muscles, palpitations, sweating, and dyspnea [47]. Resolution of GCS symptoms, a return to psychological homeostasis, and increasing carbon dioxide levels (e.g., the traditional remedy of breathing into a paper bag to calm down during a panic attack) make it possible to re-establish normal blood pH.

1.8.3. The Bainbridge and Bezoid-Jarsich Reflexes

The Bainbridge reflex opposes the Bezoid–Jarisch reflex in that it increases heart rate when atrial preload increases, as indicated by increased atrial pressure [48]. This occurs when the head is tilted far forward, when large volumes of saline are infused, the body is upside down, when legs are elevated while supine, or in reduced gravity [48]. The Bezoid–Jarisch reflex, conversely, induces reduced breath rate, bradycardia, and lower blood pressure by direct action of type-C vagal fibers, the release of neuropeptide Y receptor Y2, and afferent vagal signaling [49]. This reflex can override the baroreceptor reflex and was first observed after alkaloid injections in dogs; reduced circulation from the reflex may have evolved to provide some protection from systemic circulation of toxins [50]. This reflex can also be stimulated by nicotine (a plant alkaloid) and chronic alcohol abuse that activates the reflex via enhanced cardiac contractions due to β1-adrenergic stimulation coupled with β2-adrenergic-mediated vasodilation [51]. Clinically, it is often observed in cases of myocardial infarctions after reperfusion and is mediated by receptors localized in the right coronary artery [52]. GCS may errantly stimulate the Bezoid–Jarisch reflex, reducing respiratory rate or stimulate a premature Hering–Breuer reflex (which prevents overinflation of the lungs via vagal activation upon mechanoreception of lung stretching), which would cause a palpitation (extra systole) as the heart adapts to the new respiratory rate and pumps extra blood out with the Bainbridge reflex which activates upon sensing the extra atrial preload. Such sensations can, in hypersensitized individuals, cause panic responses that override vagal control and cause GCS symptoms via adrenaline/norepinephrine. Again, resolution of the gut-mediated vagal static and psychological symptoms allows return to homeostasis in these cases.

1.8.4. The Valsalva Reflex

The Valsalva reflex is often stimulated in clinical contexts through the Valsalva maneuver, which directly activates the vagus nerve to slow the heart rate. This reflex is useful for treating supraventricular tachycardia and exists to compensate for thoracic pressure changes encountered during defecation, straining, or sustained exhalation (e.g., playing a wind instrument) [53]. It is comprised of four distinct phases that center around thoracic pressure changes: Phase I is the strain and subsequent blood pressure increase; Phase II is the withdrawal of vagal control (allowing an SNS-mediated increase in heart rate in response to reduced venous return); Phase III is a transition phase where strain is released (causing a drop in pressure via capillary bed expansion); and Phase IV is where the reversal of the previous phase leads to a temporary spike in pressure, activating the baroreceptor reflex and returning vagal tone to slow the heart rate to normal [53]. Thus, the vagus nerve plays a key role in the Valsalva reflex and interruptions in communication caused by GCS may precipitate cardiovascular symptoms as the reflex phases lose synchronicity due to vagal static that occurs from thoracic pressure increases from gas distention/tenesmus that mimic strain, errantly activating the Valsalva reflex.
Cardiovascular reflexes are hardwired to maintain pressure and flow homeostasis via interplay between interoceptive signals and the PNS/SNS, with the vagus nerve being a key controller of the PNS response. As GCS can affect the vagus nerve via stimulation or suppression, this interference could errantly activate or precipitate partial or brief full reflex responses, causing cardiac symptoms. In cases featuring hiatal hernias, the rapid and complete resolution of cardiovascular symptoms after surgical hernia repair indicates that continuous disruption of normal vagal signaling has direct effects on the heart via these coronary reflexes. Of note, hypersensitization to cardiac symptoms can trigger panic episodes that delay return to homeostasis.

2. Gastrocardiac Syndrome as a Model System

2.1. Risk Factors

Outside of hiatal hernias or surgical sequelae (e.g., after gastric bypass), reports indicate that age, obesity, and male gender are risk factors for GCS. However, any GI pathology that increases gut distention, dyspepsia, or causes dysfunctional vagal signaling may cause GCS symptoms. As an example, infection by foodborne, pathogenic illnesses may create large volumes of gas that cause temporary or transient GCS symptoms, while abnormal gut flora seen in cases of autism may cause bloating and other disruptions in peristalsis that precipitate GCS symptoms. IBS-C patients, who experience chronic constipation may have additive risk with other factors as the buildup of pressure within the intestines due to a propensity for idiopathic gastroparesis, coupled with dysbiosis, can increase the frequency of GCS events [54]. Dysbiosis may be a significant cumulative risk factor when combined with obesity, anxiety, IBS-C, substance abuse, or other conditions that disrupt normal GI function. Of note, patients with diabetes (especially the adult obese) are well reported to have disruptions in both gut flora and digestion, with up to 1% of type 2 diabetics and 4.8% of type 1 diabetics exhibiting gastroparesis [55,56].
For this reason, GCS is an excellent model system to study the anatomic, biochemical, and electrical connections between the heart and gut through the vagus nerve. Populations at-risk for GCS may benefit from interventions that reduce individual risk factors, such as obesity or dysbiosis, while also benefitting from cognitive behavioral therapy to ablate the conditioned panic response to symptoms that can further disrupt GI activity and increase GCS event frequency.

2.2. Symptoms and Their Roots

Table 2 summarizes the common symptoms of GCS and their locations. The root cause is gas/air distention of the intestines and symptoms may be varied, depending on impacted areas of the vagus nerve. Diagnosis is made by exclusion of heart/GI pathologies (i.e., malignancies, anatomic abnormalities, hiatal hernias, surgical sequelae, infections, etc.) and usually has an IBS comorbidity, which exacerbates the GI symptoms. As IBS is itself a diagnosis of exclusion, a colonoscopy rules out active infection and other organic causes, while a sampling of fluid from the small intestinal transition zone (cecum) can enable the culturing and identification of specific bacterial populations associated with SIBO. A psychiatric workup is also recommended as IBS sufferers are three times more likely to have psychiatric comorbidities (anxiety and depression, or both) [30]. Gastroparesis and IBS-C have overlapping symptoms, and exclusionary testing must be done to remove co-morbid gastroparesis as a differential diagnosis, especially in diabetics or the obese.

2.3. Causes

GCS is most likely a multifactorial condition that combines risk factors normally associated with digestive problems (age, obesity) and some form of dysbiosis/dyspepsia/constipation (IBS-C), combined with some psychological pathology (e.g., anxiety) that causes hypersensitization to the symptoms and subsequent disruption of GI motility that perpetuates the cycle in a positive-feedback loop. Essentially, non-hernia/non-surgical side effect GCS is a disease of air and/or gas in the intestines and all symptoms stem from the pressurization of the intestines that push up the stomach into the diaphragm, impinging on the thoracic organs and creating vagal static that imbalances the delicate PNS/SNS balance (Figure 2).
Dysbiosis is a strong factor in GCS, as disruptions in gut flora may precipitate mood disorders, facilitate overgrowth of opportunistic or transitory pathogens, inhibit or dysregulate peristalsis, create gut-distending flatus, and promote gut inflammation that irritates or causes pain and tenesmus. Dysbiosis may come as a sequela of food poisoning, from overuse of antibiotics, or enrichment of deleterious bacteria by poor diet. Initial disruptions in peristalsis and the migrating motor complex (peristaltic waves that push material unidirectionally through the intestines towards the anus) may cause a backwash of methanogenic archaebacteria (e.g., Methnobrevibacter smithii) and nominally harmless bacteria (e.g., Escherichia coli-K12) that feed on the hydrogen byproducts of bacterial sugar metabolism to generate large volumes of methane gas that can both distend the gut and force constipation through slowing of peristalsis by a putative effect on the cholinergic receptors within the intestinal wall [57,58]. This small intestinal bacterial overgrowth (SIBO), while not currently recognized as a diagnosis, nevertheless has reproducible lab testing and breath exhalation spectrometry that measures ratios of hydrogen to methane can be invaluable for diagnosing SIBO as an adjunct to IBS-C.
The gut bacteria that are most implicated in SIBO are Escherichia and Klebsiella spp., which were found to be key node disruptors in duodenal microbial communities sampled from SIBO patients, while Enterobacteriaceae spp. were reported to increase hydrogen gas production (a food source for methanogens in SIBO-affected guts) [59]. Leite and colleagues recently specified K. aerogenes, K. pneumoniae, and E. coli BL21(DE3) as especially associated with SIBO-modified gut flora [59].
IBS-C is an overarching pathology that intersects with GCS via microbial interactions with the CNS through the GI-vagus nerve axis. Even outside of gut-distending methane generation, disrupted gut flora may also affect mood that mediates IBS and subsequent GCS. This was seen when Appleton reported on previous studies where Campylobacter jejuni administration in rats at doses unlikely to cause primary symptoms resulted in anxious behavior [31]. Conversely, Lactobacillus rhamnosus in zebrafish positively affected serotonin and trials in humans with Lactobacillus spp. supplementation have shown some benefits to alleviating stress, exhaustion, and depression (albeit with mixed results) [31]. Specific bacteria species found to be enriched in the gut flora of anxiety patients include Bacteroides, Fusobacterium, and Escherichia-Klebsiella spp., while reductions in Gemmiger, some Ruminococcus, and Veillonella spp. are also associated with anxiety [60]. Of note, Escherichia-Klebsiella spp., associated with both SIBO and anxiety, are foodborne pathogens and may represent the sequela variant of SIBO (methane-dominant) after recovery from food poisoning.
Clearly, modulation of the CNS via gut signaling is a central function of the microbiome in addition to its myriad other immune- and digestion-related duties. Thus, IBS-related dysbiosis may carry the quadruple impact of serotonin dysregulation (arrythmic peristalsis); digestive upset/gas production (thoracic pressure increases); the generation of methane that ablates peristalsis; and the enhancement of mood disorders that precipitate digestive motility pathologies through stress-mediated disruptions. However, even outside of the gut flora influence, psychological disorders like general anxiety disorder, depression, addiction, or bipolar disorder may increase the risk of IBS-mediated GCS additively when other factors, such as obesity, are also in play [61]. It is currently debatable as to whether the dysbiosis precipitates mood disorders or whether mood disorders precipitate dysbiosis; clinicians are advised to always assume that the two conditions are related and the voluminous number of reports that serotonin-regulating drugs also affect GI function is evidence to support that treatment route. Care must be taken when diagnosing IBS-C, however, since gastroparesis (which can slow gastric emptying and create intense bloating or cramping that drives GCS events) symptoms often overlap or are co-morbid with IBS [62]. Non-IBS, non-surgical-related gastroparesis can be a result of diabetes, herpes, Salmonella spp. infection, or other enteroviruses [63].
Aerophagia (air swallowing) is most likely a contributive cause of GCS symptoms, as pockets of gas trapped in the intestines can increase pressure and impingement into the diaphragmatic space. Excessively consumed air via diet or inadequate mastication (e.g., carbonated sodas, gulping of food, or gum chewing) is normally expelled from the stomach by eructation (burping) but sources of forced air, such as continuous positive airway pressure (CPAP) devices used to treat sleep apnea, may overcome this reflex due to extended use [64]. IBS may also introduce air into the GI tract by GERD symptoms, the disruption of motility that would normally expel the air as flatus, or obsessive-compulsive disorders associated with anxiety and IBS that cause habitual air gulping. The development of visceral hypersensitivity to distension from such swallowed air may further cause distress and perpetuate the GCS cycle by enhancing the psychological component [65].
Mechanical/anatomic causes cannot be overlooked in GCS. Hiatal hernias are an often-reported cause of GCS in case reports while surgical procedures that shorten intestines or damage nerve plexuses may inadvertently cause GCS through disruptions in digestion or the gut flora [66,67]. Hiatal hernias, once repaired, cease to cause GCS symptoms, although secondary psychological or gut flora sequelae may persist and consistently reactivate GCS at a lower activity level through previously mentioned mechanisms. Gastroparesis from GLP-1 agonists used for weight loss, or as a neurological sequela from surgery or infection, may also be addressed clinically to resolve poor digestion that can exacerbate GCS [68].

3. Treatment of Non-Surgical GCS: Multi-Pronged by Design

Effective GCS treatment in the case literature is often conducted surgically, as the majority of reports are centered around hiatal hernias. In cases where anatomic abnormalities are causing GCS, surgery is indeed the correct strategy and the success rate reported after cases is proof. GCS resulting from pharmaceutical or surgical side effects may also be experienced (e.g., liraglutide was found to carry an HR of 3.67 for gastroparesis versus controls) and these types of sequelae, which may persist, are also addressed pharmaceutically or with medication withdrawal [68]. However, as GCS is usually affected and exacerbated by numerous other demographic, situational, and lifestyle factors, the treatment strategies must also be diverse to address each component.
First, addressable risk factors are to be examined and a treatment plan enacted. Obesity, which creates strictures around the abdomen that reduce expansion room for intestinal distention can be approached with diet and exercise. Bariatric surgeries, in addition to the possible anatomic and flora disruptions that may precipitate GCS, may cause nutrition shortages that drive overeating and dyspepsia from shorter intestines, smaller stomachs with less acid, or other side effects (e.g., gastroparesis). Age and sex factors can be mitigated with diet and exercise plans that take into account the less efficient digestion of middle and elderly ages, especially in post-menopausal women. Patients who have anxiety or other mental disorders can be treated with cognitive behavioral therapy or medication, with observation and titration to ensure that psychoactive drugs do not interfere with the digestion. A moderate exercise program, in all risk factor cases, is the top recommendation, as low-to-moderate intensity cardiovascular exercise (e.g., fast walking, hiking, cycling) has consistently shown benefits across every body system. IBS-mediated dyspepsia, peristalsis, and other digestive issues have been shown to lessen with exercise as motion stimulates the digestive system and alleviates symptoms of depression [69]. A 2024 meta-review of 218 studies with 14,170 total patients found that walking, jogging, strength training, tai chi, and mixed aerobics all produced beneficial treatment effects for depression on par with medications and psychotherapy [70]. While a meta-review of 25 clinical trials with 1831 participants found little evidence to support exercise as a therapy equivalent to medication for anxiety, methodology concerns of the included studies were cited as a reason for the ambiguous results [71]. In spite of these reports concerning anxiety, the systemic benefits of moderate exercise may attack both the physiological and psychological causes of GCS in addition to maintaining overall health.
Next, diet is a key factor in GCS interventions as SIBO or dysbiosis secondary to foodborne illness can alter the gut flora and exacerbate GCS episodes. In these cases, a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet also low in simple sugars is recommended, as reports have shown beneficial effects for IBS-C as far as symptomatic improvements and promotion of bowel movements [72]. Counter to traditional advice, dietary fiber is to be eliminated from the diet since both soluble and insoluble fiber may worsen IBS-C/SIBO symptoms. Avoidance of sorbitol and other sugar alcohol emulsifiers found in ultraprocessed foods may also provide relief from IBS symptoms as a combined FODMAP and processed food avoidance diet remove the primary nutrition source of methanogenic bacteria (hydrogen from fermentation of sugar); reductions in gut methane will relieve both gas distention and constipation. Lists of low-FODMAP foods are readily available online and natural, surfactant emulsifiers like lecithin, which are converted to acetylcholine (stimulating peristalsis), were reported to improve IBS symptoms in a clinical study of 69 participants [16,73]. Fasting strategies that encourage the migrating motor complex to sweep the intestines, as well as starve methanogens of hydrogen, may also provide some relief while addressing overeating or binge eating issues driven by mental disorders that could exacerbate GCS.
Gut flora manipulation, through pro- and pre-biotic nutriceuticals, is projected to reach USD $85 billion in global market size by 2027 [74]. Supplements with blends of enteric and transitory bacteria are also available by prescription in most countries (e.g., Visbiome, Medilac, MiyaBM, Biofermin S) and are clinically tested and proven for their indicated usage. In Japan alone, 65 probiotic products have been approved for sale under the “foods for specialized health use” regulatory category and this market is expected to continue growth [75]. Thus, there is no shortage of flora-altering products available to choose from. However, in cases of SIBO, removal of methanogens or other problematic species is first recommended to avoid relapse. Additionally, administration of probiotics without first eliminating the methanogen overgrowth may result in worsening of gas production, tenesmus, pain, and GCS exacerbations. Once the offending bacteria are gone, replenishment with probiotics is theoretically the optimal protocol although no large-scale studies on specific probiotics and SIBO resolution/relapse prevention currently exist. Eradication of methanogens is often clinically accomplished with rifaximin, a broad-spectrum antibiotic that has very low bioavailability and attacks bacteria on the surface of the intestinal lumen. Intended to treat traveler’s diarrhea, it has been shown by a meta-review of six trials to have overall benefits even if it did not perform better than controls for IBS symptoms (such as pain and vomiting) or other medication side effects [76]. Herbal or other natural treatments (such as coated garlic pills, thyme oil, and berberine) are purported to be as successful as rifaximin, but a recent study that examined herbal supplements found that gas levels were not improved even though overall remission benefits were seen mostly in methane-dominant SIBO patients [77]. As methane-dominant SIBO can drive constipation (IBS-C) and greatly exacerbate GCS, these herbal treatments require longer-duration studies and larger, well-controlled comparisons to rifaximin before becoming a standard of care. Also required are studies of which specific enteric strains are best at preventing relapse of SIBO/IBS that could exacerbate GCS symptoms.
Pharmaceutical interventions focused on cardiac symptom relief are readily available with the current pharmacopeia. However, in GCS, since cardiovascular symptoms are entirely linked to the GI tract condition, using beta blockers or other cardiovascular drugs to ablate those specific symptoms is contraindicated; it is sometimes simpler to resolve GI issues, such as food intolerance or gastroparesis, that are causative. Likewise, starting psychoactive drugs in patients who manifest anxiety or other disorders during chronic GCS may be unhelpful as disruptions in peristalsis from serotonin-affecting medications may prevent full resolution of GCS. It is far more helpful to remove the GI root causes; once there is no mechanical activation of anxiety/panic through GCS, cognitive behavioral therapy and desensitization therapy will most likely provide long-term relief without side effects.
A plethora of medications address GI symptoms that promote GCS episodes. Activated charcoal may adsorb intestinal gas, especially methane, and ablate constipation but long-term use may increase risks of intestinal blockage, alteration of medication metabolism, or ingress into the lungs during episodes of nighttime GERD often seen in IBS patients or in users of CPAP devices. Incomplete digestion that increases gut fermentation and subsequent gas release can be treated with digestive enzymes, such as pancrelipase or proteases (found in over-the-counter enzyme formulations), and laxatives (osmotic like magnesium or stimulant like sennosides) may be occasionally used for rescue if constipation is chronic. In severe cases, dopamine antagonists that promote peristalsis may provide relief for gastroparesis, nausea, and GERD. Bromopride and metoclopramide are dopamine antagonists used to treat gastroparesis that increase GI motility, especially in the duodenum and jejunum [78], while levosulpiride, a benzamide-class dopamine antagonist, is often recommended for anxiety-induced GI dysfunction as it carries anti-psychotic effects [79]. Prucalopride, a benzofurane derivative, is a serotonin agonist that treats constipation via peristalsis promotion but without cardiac effects [79]. Domperidone is a dopamine antagonist derived from piperidine that treats vomiting and has no CNS effects but may have cardiac side effects at high doses (regulated in EU) [79]. Cinitapride, is a 5-HT prokinetic that promotes peristalsis and is derived from benzamide [79]. These drugs are summarized, along with side effects, in Table 3.
GCS treatment must be tailored to each patient but will most likely feature therapies that address the GI, cardiac, and psychological triad that comprise this syndrome.

4. Conclusions and Prospects

GCS consists of the heart–gut–psychiatric triad, connected by the vagus nerve, and affects mostly overweight, middle-aged, males or those with hiatal hernias. While surgical correction of anatomic irregularities in the GI system can be curative and GCS from iatrogenic causes can be addressed with standard pharmacopeia, the unique blend of causative factors (psychiatric disorders, foodborne illness sequelae, etc.) must be considered for each patient. Large-scale, diverse, and clinically relevant studies are required to create standard diagnostic and treatment options to address GCS in medical settings.

Author Contributions

Conceptualization, B.J.M. and R.S.; methodology, B.J.M. and Y.H.; investigation, B.J.M., R.S. and Y.K.; data curation, B.J.M. and Y.K.; writing—original draft preparation, B.J.M.; writing—review and editing, B.J.M., R.S., Y.K., H.K. and Y.H.; visualization, B.J.M.; supervision, H.K. and Y.H.; project administration, H.K. and Y.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created.

Acknowledgments

The authors dedicate this manuscript to all who suffer from gastrocardiac syndrome. May we all find relief.

Conflicts of Interest

The authors declare no conflicts of interest.

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Encyclopedia 04 00113 g001
Figure 1. Vagus and spinal nerves as coordinated and balanced opposing forces: The spinal nerves (right) activate the sympathetic nervous system to control the lungs (T1–T4), heart (T2–T4), stomach (T5–T8), the gallbladder and intestines (T9–T11) and the rectum (L1–L2). The vagus trunk (left) activates the parasympathetic nervous system with the indicated branches in the same organs. Afferent and efferent pathways in both systems allow for real-time monitoring and control of innervated organs. Created in BioRender.
Figure 1. Vagus and spinal nerves as coordinated and balanced opposing forces: The spinal nerves (right) activate the sympathetic nervous system to control the lungs (T1–T4), heart (T2–T4), stomach (T5–T8), the gallbladder and intestines (T9–T11) and the rectum (L1–L2). The vagus trunk (left) activates the parasympathetic nervous system with the indicated branches in the same organs. Afferent and efferent pathways in both systems allow for real-time monitoring and control of innervated organs. Created in BioRender.
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Figure 2. Pressure as a theoretical key factor in gastrocardiac syndrome: when pressure in the gut is normal, the SNS/PNS maintain the homeostasis required for the push–pull innervation of the gut that coordinates peristalsis, segmentation, and secretion (left). When, from dysbiosis or other factors, the pressure in the intestines increases (red up arrows), it forces the stomach into the diaphragm, which then increases thoracic pressure and may affect the pulmonary system (right). The vagus nerve static from mechanical pressure imbalances the SNS/PNS homeostasis required for digestion, causing SNS dominance, while errant and intermittent activation of the PNS system causes cardiac symptoms. SNS, sympathetic nervous system; PNS, parasympathetic nervous system. Created in BioRender.
Figure 2. Pressure as a theoretical key factor in gastrocardiac syndrome: when pressure in the gut is normal, the SNS/PNS maintain the homeostasis required for the push–pull innervation of the gut that coordinates peristalsis, segmentation, and secretion (left). When, from dysbiosis or other factors, the pressure in the intestines increases (red up arrows), it forces the stomach into the diaphragm, which then increases thoracic pressure and may affect the pulmonary system (right). The vagus nerve static from mechanical pressure imbalances the SNS/PNS homeostasis required for digestion, causing SNS dominance, while errant and intermittent activation of the PNS system causes cardiac symptoms. SNS, sympathetic nervous system; PNS, parasympathetic nervous system. Created in BioRender.
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Table 1. Review of Extant Case Literature. COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; PSVT, paroxysmal supraventricular tachycardia; PVC, premature ventricular contraction; SVT, supraventricular tachycardia; T2D, type 2 diabetes.
Table 1. Review of Extant Case Literature. COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; PSVT, paroxysmal supraventricular tachycardia; PVC, premature ventricular contraction; SVT, supraventricular tachycardia; T2D, type 2 diabetes.
CaseYearAuthorAge/SexSymptomsHistoryCauseTreatmentResolved?Ref.
12024Khreshi53/MBradycardia, GERDT2D, goutVagal tonePPINo[2]
22023Natale40/MSyncope, bradycardiaNoneIntragastric balloonExcretionYes[3]
32023Bhandari57/FChest pain, ventricular bigeminy, bradycardia, mitral regurgitationTakotsubo cardiomyopathy, hiatal hernia, hypertension, hyperlipidemiaHiatal herniaSurgeryYes[4]
42023Noom60/MSVT with PVCs, hypertensive urgency, tachycardiaEsophageal stricture, hiatal hernia, GERD, arrythmiasHiatal herniaSurgeryYes [5]
52022John65/MAbdomen pain, dyspnea, tachycardiaNone ListedStomach compressionSurgeryYes[6]
62021Qureshi54/FTachycardia, bloating, distention, nauseaHypertension, dyspepsia, PSVTDyspepsiaLifestyle change, omeprezoleYes [7]
72020Mehta62/FPalpitations, PVC, GERDObesity, hiatal hernia, dyslipidemiaHiatal herniaSurgeryYes[8]
82018Saeed75/FDizziness, gut distention, bradycardiaHypertension, COPD, constipation, dementiaHiatal HerniaNasogastric tube, pacemakerYes [9]
Table 2. Typical GCS Symptoms. PVC, premature ventricular contraction (extra systole); GERD, gastroesophageal reflux disease.
Table 2. Typical GCS Symptoms. PVC, premature ventricular contraction (extra systole); GERD, gastroesophageal reflux disease.
LocationSymptom
ChestTachycardia
Bradycardia
Arrythmia
PVC
Dyspnea
AbdomenBloating
GERD
Fullness
Dyspepsia
Vomiting
Pain
Constipation
Meteorism
PsychologicalAnxiety
Panic
Depression
Insomnia
Dizziness
Nausea
Table 3. A selection of pharmaceutical treatments for GCS symptoms. QT, the Q-T wave on an electrocardiogram.
Table 3. A selection of pharmaceutical treatments for GCS symptoms. QT, the Q-T wave on an electrocardiogram.
DrugPubChem IDIndicationClassSide EffectRef.
Activated charcoal481108125Gas Inert SubstanceIntestinal blockage, lung ingress -
Pancrelipase-DyspepsiaEnzymeConstipation, nausea -
Protease-DyspepsiaEnzymeDiarrhea, nausea -
MagnesiumVariousConstipationOsmotic laxativeDiarrhea-
Sennosides656822ConstipationStimulant laxativeDiarrhea, stomach cramps -
Bromopride3016754GastroparesisDopamine antagonistDrowsiness, fatigue, dry mouth, diarrhea or constipation[78,79]
Metoclopramide4168GastroparesisDopamine antagonistDrowsiness, kidney problems (in elderly), fatigue, dry mouth, diarrhea or constipation [78]
Levosulpiride688272Gastroparesis, anxietyDopamine antagonistHeadache, fatigue, altered heart rate [79]
Prucalopride3052762ConstipationDopamine antagonistStomach pain, diarrhea, dizziness, suicidal thoughts[79]
Domperidone3151Vomiting, constipationDopamine antagonistEdema in feet, fatigue, hot flashes, cardiac QT prolongation [79]
Cinitapride68867Constipation, gastroparesis5-HT ProkineticHeadache, dizziness, nausea, vomiting, hypertension if aspirin is taken[79]
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Mathis, B.J.; Suzuki, R.; Kuroda, Y.; Kato, H.; Hiramatsu, Y. Understanding the Gut-Heart Axis in Roemheld Syndrome: Mechanisms and Clinical Insights. Encyclopedia 2024, 4, 1721-1738. https://doi.org/10.3390/encyclopedia4040113

AMA Style

Mathis BJ, Suzuki R, Kuroda Y, Kato H, Hiramatsu Y. Understanding the Gut-Heart Axis in Roemheld Syndrome: Mechanisms and Clinical Insights. Encyclopedia. 2024; 4(4):1721-1738. https://doi.org/10.3390/encyclopedia4040113

Chicago/Turabian Style

Mathis, Bryan J., Ryuji Suzuki, Yukihito Kuroda, Hideyuki Kato, and Yuji Hiramatsu. 2024. "Understanding the Gut-Heart Axis in Roemheld Syndrome: Mechanisms and Clinical Insights" Encyclopedia 4, no. 4: 1721-1738. https://doi.org/10.3390/encyclopedia4040113

APA Style

Mathis, B. J., Suzuki, R., Kuroda, Y., Kato, H., & Hiramatsu, Y. (2024). Understanding the Gut-Heart Axis in Roemheld Syndrome: Mechanisms and Clinical Insights. Encyclopedia, 4(4), 1721-1738. https://doi.org/10.3390/encyclopedia4040113

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