What else can cause Long QT?
KCNE1
Inherited or sporadic KCNE gene mutations can cause Romano-Ward syndrome (heterozygotes) and Jervell Lange-Nielsens syndrome (homozygotes). Both these syndromes are characterized by Long QT syndrome, a delay in ventricular repolarization. In addition, Jervell and Lange-Nielsen syndrome also involves bilateral sensorineural deafness. Mutation D76N in the KCNE1 protein can lead to long QT syndrome due to structural changes in the KvLQT1/KCNE1 complex, and people with these mutations are advised to avoid triggers of cardiac arrhythmia and prolonged QT intervals, such as stress or strenuous exercise.
Effects of overtime
Long-term effects were researched by The University of Texas Health Science Center at Houston. They studied the link between overtime and the increased risk of cardiovascular disorder (CVD) events. Their results included evidence that showed that for people who worked at least 10 years for each additional hour worked, starting from the 46th hour, his or her risk of a CVD event increased by 1%. In addition to these health risks, María Beniell, who received her Ph.D. in Economics from the Center for Monetary and Financial Studies (CEMFI), researched the correlation between working long hours and the likelihood of individuals smoking, drinking, having a high body mass index (BMI), and being less physically active. The long-term effects of alcohol consumption include increased on-the-job injuries and loss of productivity, family problems, risk of high blood pressure, stroke, other cardiovascular diseases, and more. The effects of smoking, in addition to similarities of the effects of alcohol, include increased risk of heart attacks, emphysema, and a large amount of cancers.
Ondansetron
Use of ondansetron has been associated with prolongation of the QT interval, which can lead to a potentially fatal heart rhythm known as "torsades de pointes". Although this may happen in any person with any formulation, the risk is most salient with the injectable (intravenous) form of the drug and increases with dose. The risk is also higher in people taking other medicines that prolong the QT interval, as well as in people with congenital long QT syndrome, congestive heart failure, and/or bradyarrhythmias. As such, single doses of injectable ondansetron should not exceed 16 mg at one time. (Oral dosing recommendations remain intact, including the recommendation of a single 24-mg oral dose when indicated.) Electrolyte imbalances should be corrected before the use of injectable ondansetron. People are cautioned to seek immediate medical care if symptoms such as irregular heartbeat/palpitations, shortness of breath, dizziness, or fainting occur while taking ondansetron.
HERG
When this channel's ability to conduct electrical current across the cell membrane is inhibited or compromised, either by application of drugs or by rare mutations in some families, it can result in a potentially fatal disorder called long QT syndrome. Conversely, genetic mutations that increase the current through these channels can lead to the related inherited heart rhythm disorder Short QT syndrome. A number of clinically successful drugs in the market have had the tendency to inhibit hERG, lengthening the QT and potentially leading to a fatal irregularity of the heartbeat (a ventricular tachyarrhythmia called torsades de pointes). This has made hERG inhibition an important antitarget that must be avoided during drug development.
Coronary ischemia
CAD can be contracted over time. Certain factors play into this, for example, a family history of CAD. Other factors include smoking, high blood pressure, diabetes,obesity, inactive lifestyle and high cholesterol.
Long QT syndrome
All forms of LQTS involve an abnormal repolarization of the heart, which causes differences in the refractory period of the heart muscle cells (myocytes). After-depolarizations (which occur more commonly in LQTS) can be propagated to neighboring cells due to the differences in the refractory periods, leading to re-entrant ventricular arrhythmias.
Jervell and Lange-Nielsen syndrome
Jervell and Lange-Nielsen syndrome is caused by mutations in the "KCNE1" and "KCNQ1" genes. The proteins produced by these two genes work together to form a potassium channel that transports positively charged potassium ions out of cells, which is called the slow delayed rectifier potassium current. The movement of potassium ions through these channels is critical for maintaining the normal functions of the inner ear and cardiac muscle. JLNS is an autosomal recessive disorder meaning that two copies of the genetic mutation are required to produce the full syndrome. Mutations in the same genes can produce milder Romano-Ward forms of long QT syndrome if only a single copy of the genetic mutation is inherited.
Annuloaortic ectasia
Annuloaortic ectasia is a dilation of the proximal ascending aorta and aortic annulus. It may cause aortic regurgitation, thoracic aortic dissection, aneurysm and rupture. It is often associated with connective tissue diseases like Marfan syndrome and Ehlers Danlos Syndrome. It can also be a complication due to tertiary syphilis. In tertiary syphilis the aortic root becomes so dilated that the aortic valve becomes incompetent and cor bovinum results.
KCNE2
KCNE2 was originally discovered to regulate hERG channel function. KCNE2 decreases marcoscopic and unitary current through hERG, and speeds hERG deactivation. hERG generates IKr, the most prominent repolarizing current in human ventricular cardiomyocytes. hERG, and IKr, are highly susceptible to block by a range of structurally diverse pharmacological agents. This property means that many drugs or potential drugs have the capacity to impair human ventricular repolarization, leading to drug-induced Long QT syndrome (LQTS). KCNE2 may also regulate hyperpolarization-activated, cyclic-nucleotide-gated (HCN) pacemaker channels in human heart and in the hearts of other species, as well as the Cav1.2 voltage-gated calcium channel.
Romano–Ward syndrome
Romano–Ward syndrome is the most common subtype of Long QT syndrome, a genetic heart condition that affects the electrical properties of heart muscle cells. The condition makes those affected at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death.
Effects of overtime
For Coronary Heart Disease (CHD), a meta-analysis of four prospective studies published in 2012 found a 1.4-fold increased risk of CHD associated with long working hours. The investigators also noted that this association was higher for men than women. They hypothesized underlying mechanisms for this association may include longer exposure to stress, sleep deprivation, and / or dysregulation of the HPA axis causing an increase in cortisol production. They also noted that this estimate might have been biased for several reasons. One reason could have been if workers with underlying CHD reduced their working hours in the years before a CHD event. A second reason could be due to confounding of SES. A meta-analysis adjusting for these factors found the risk of a CHD event to be 1.13 instead. Furthermore, the study authors also found a 1.3-times higher risk for those working long hours.
Fluconazole
Fluconazole therapy has been associated with QT interval prolongation, which may lead to serious cardiac arrhythmias. Thus, it is used with caution in patients with risk factors for prolonged QT interval, such as electrolyte imbalance or use of other drugs that may prolong the QT interval (particularly cisapride and pimozide).
Quantium Medical Cardiac Output
What can cause a CO variation?
Romano–Ward syndrome
Romano-Ward syndrome is the most common form of inherited long QT syndrome, affecting an estimated 1 in 7,000 people worldwide.
Long QT syndrome
A large number of mutations have been characterized as leading to or predisposing to LQT3. Calcium has been suggested as a regulator of "SCN5A" protein, and the effects of calcium on "SCN5A" may begin to explain the mechanism by which some these mutations cause LQT3. Furthermore, mutations in "SCN5A" can cause Brugada syndrome, cardiac conduction disease, and dilated cardiomyopathy. In rare situations, some affected individuals can have combinations of these diseases.
Solifenacin
Long QT syndrome is not a contraindication although solifenacin, like tolterodine and darifenacin, binds to hERG channels of the heart and may prolong the QT interval. This mechanism appears to be seldom clinically relevant.
Long QT syndrome
The arrhythmias that lead to faints and sudden death often occur in response to specific circumstances, in part determined by which genetic variant is responsible for the condition. Some forms of LQTS lead to arrhythmias in response to exercise or mental stress (LQT1), while in other forms the arrhythmias are more likely to occur following a sudden loud noise (LQT2). In contrast, in some other forms of LQTS arrhythmias are more likely to occur during sleep, or immediately upon waking (LQT3).
Long QT syndrome
Genotype and QT interval duration are independent predictors of recurrence of life-threatening events during beta-blocker therapy. To be specific, the presence of QTc >500 ms and LQT2 and LQT3 genotype are associated with the highest incidence of recurrence. In these patients, primary prevention with use of implantable cardioverter-defibrillators can be considered.
QT interval
Like the R–R interval, the QT interval is dependent on the heart rate in an obvious way (i.e., the faster the heart rate, the shorter the R–R interval and QT interval) and may be adjusted to improve the detection of patients at increased risk of ventricular arrhythmia. Modern computer-based ECG machines can easily calculate a corrected QT (QTc), but this correction may not aid in the detection of patients at increased risk of arrhythmia, as there are a number of different correction formulas.
Caveolin 3
Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), HyperCKemia, distal myopathy or rippling muscle disease (RMD). Other mutations in Caveolin causes Long QT Syndrome or familial hypertrophic cardiomyopathy, although the role of Cav3 in Long QT syndrome has recently been disputed.
Short QT syndrome
Those affected by short QT syndrome (SQT) have an increased risk of developing abnormal heart rhythms. These abnormal heart rhythms often occur at a young age. They may take relatively benign forms such as atrial fibrillation, leading to symptoms of palpitations, breathlessness, or fatigue. Accordingly, atrial fibrillation presenting in a newborn should raise the suspicion of short QT syndrome. In addition, far more dangerous heart rhythm disturbances such as ventricular fibrillation can also occur in those with short QT syndrome, leading to blackouts or even sudden death. More than a third of those with short QT present with ventricular arrhythmias or sudden cardiac death, while one in five cases are detected during family screening, and one in five cases are found incidentally after an electrocardiogram (ECG) has been recorded for another reason.
Overlap syndrome
In cardiology, genetic conditions such as Brugada syndrome can share features with related disorders caused by mutations in the same gene. An overlap syndrome can be seen whereby a mutation in the SCN5A gene encoding the cardiac sodium channel causes a reduction in the peak sodium current leading to the typical ECG features of Brugada syndrome, but which simultaneously increases the sustained late sodium current leading to the ECG features of Long QT syndrome type 3. Brugada syndrome can also overlap with arrhythmogenic cardiomyopathy due to certain mutations in the plakophilin gene.
Ibogaine
Ibogaine causes long QT syndrome at therapeutic doses, apparently by blocking hERG potassium channels in the heart.
Laminitis
The mechanism remains unclear and is the subject of much research. Three conditions are thought to cause secondary laminitis:Inflammatory events that are associated with laminitis include sepsis, endotoxemia, retained placenta, carbohydrate overload (excessive grain or pasture), enterocolitis, pleuropneumonia, and contact with black walnut shavings. In these cases, there is an increase in blood flow to the hoof, bringing in damaging substances and inflammatory cells into the hoof.Endocrinopathy is usually the result of improper insulin regulation, and is most commonly seen with pituitary pars intermedia dysfunction (also called equine Cushing's syndrome) and equine metabolic syndrome (EMS), as well as obesity and glucocorticoid administration. In cases of EMS, most episodes occur in the spring when the grass is lush.Mechanical laminitis starts when the hoof wall is pulled away from the bone or lost, as a result of external influences. Mechanical laminitis can occur when a horse habitually paws, is ridden or driven on hard surfaces ("road founder"), or in cases of excessive weight-bearing due to compensation for the opposing limb, a process called "support limb laminitis". Support limb laminitis is most common in horses suffering from severe injury to one limb, such as fracture, resulting in a non-weight bearing state that forces them to take excessive load on the opposing limb. This causes decreased blood flow to the cells, decreasing oxygen and nutrient delivery, and thus altering their metabolism which results in laminitis.
Escitalopram
Citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with congenital long QT syndrome or known pre-existing QT interval prolongation, or in combination with other medicines that prolong the QT interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be corrected before starting treatment. In December 2011, the UK implemented new restrictions on the maximum daily doses at 20 mg for adults and 10 mg for those older than 65 years or with liver impairment. There are concerns of higher rates of QT prolongation and torsades de pointes compared to other SSRIs. The U.S. Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessor citalopram.
Long QT syndrome
Factors which prolong the QT interval are additive, and genetic variants may make those who carry them more susceptible to drug-induced LQT. A combination of factors can cause a greater degree of QT prolongation than each factor alone.
Quinine
Quinine can cause unpredictable serious and life-threatening blood and cardiovascular reactions including low platelet count and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), long QT syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia. Some people who have developed TTP due to quinine have gone on to develop kidney failure. It can also cause serious hypersensitivity reactions include anaphylactic shock, urticaria, serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, granulomatous hepatitis, and itchiness.
QT interval
Hypothyroidism, a condition of low function of the thyroid gland, can cause QT prolongation at the electrocardiogram. Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias.
Prolonged labor
Cephalopelvic Disproportion is the issue that arises when the fetus' body or head is to large to pass through the mother's pelvis. Common conditions that lead to CPD are diabetes, multiple pregnancies, small or abnormally shaped pelvis, atypical fetal positions, hereditary factors, and first time pregnancies. Medical professionals can usually estimate if fetal size is too large based on ultrasounds, but they are not always entirely accurate. Doctors typically determine CPD when labor begins and the use of oxytocin is not effective. The safest way for delivery to take place when CBD is a factor is through cesarean sections. In terms of medical care, preventative treatment or assisted delivery are typically the first options doctors consider. There is usually no quick fix to prolonged labor, especially if preventative measures do not revert the mother back to normal labor. Often, medical professionals have to resort to intervention methods. If the state of the fetus and mother are not especially serious or threatening to their health, doctors will perform assisted vaginal deliveries.
Long QT syndrome
Mutations to "KCNQ1" can be inherited in an autosomal dominant or an autosomal recessive pattern in the same family. In the autosomal recessive mutation of this gene, homozygous mutations lead to severe prolongation of the QT interval (due to near-complete loss of the I ion channel), and are associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the Jervell and Lange-Nielsen syndrome.
Furthermore, LQT1 patients also have an endocrine phenotype. During a glucose load, LQT1 patients respond with an exaggerated insulin secretion followed by a temporary insulin resistance. When the resistance diminishes, LQT1 patients are at risk for hypoglycaemia.
QT interval
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Artemether/lumefantrine
Food, in particular fat, enhances the absorption of both artemether and lumefantrine, and patients are advised to take the tablets with food as soon as a meal can be tolerated. Coartem has a potential to prolong the QT interval, so combinations with other drugs having that property can cause irregular heartbeat, potentially leading to lethal ventricular fibrillation. The combination with halofantrine, another antimalarial, can cause a life-threatening QT prolongation. Drugs and other substances influencing the activity of the liver enzyme CYP3A4, including grapefruit juice, can either increase or lower blood levels of artemether/lumefantrine, depending on the sort of substance. This can either lead to more severe side effects or to reduced efficiency.
Long QT syndrome
As the QT prolonging effects of both genetic variants and acquired causes of LQTS are additive, those with inherited LQTS are more likely to experience TdP if given QT prolonging drugs or develop electrolyte problems such as low potassium. Similarly, those taking QT prolonging medications are more likely to experience TdP if they have a genetic tendency to a prolonged QT interval, even it this tendency is concealed. Arrhythmias occur more commonly in drug-induced LQTS if the medication in question has been rapidly given intravenously, or if high concentrations of the drug are present in the person's blood. The risk of arrhythmias is also higher if the person receiving the drug has heart failure, is taking digitalis, or has recently been cardioverted from atrial fibrillation. Other risk factors for developing torsades de pointes among those with LQTS include female sex, increasing age, pre-existing cardiovascular disease, and abnormal liver or kidney function.
Anorexia (symptom)
Anorexia is a relatively common condition that can lead patients to have dangerous electrolyte imbalances, leading to acquired long QT syndrome which can result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Care must be taken under such circumstances to avoid potentially fatal complications of refeeding syndrome.
Long QT syndrome
The diagnosis of LQTS is not easy since 2.5% of the healthy population has prolonged QT interval, and 10–15% of LQTS patients have a normal QT interval. A commonly used criterion to diagnose LQTS is the LQTS "diagnostic score", calculated by assigning different points to various criteria (listed below). With four or more points, the probability is high for LQTS; with one point or less, the probability is low. A score of two or three points indicates intermediate probability.
Masonic Medical Research Laboratory
In 2000 the MMRL research team uncovered evidence linking Sudden Infant Death Syndrome to a congenital heart defect, the Long QT syndrome (LQTS) published in The New England Journal of Medicine. That year they also found experimental evidence, confirmed by later research, that some forms of early repolarization could result in the development of life-threatening arrhythmias.
U wave
Prominent U waves are most often seen in hypokalemia but may be present in hypercalcemia, thyrotoxicosis, or exposure to digitalis, epinephrine and Class 1A and 3 antiarrhythmics, as well as in congenital long QT syndrome, and in the setting of intracranial hemorrhage.
Long QT syndrome
LQT1 is the most common type of long QT syndrome, making up about 30 to 35% of all cases. The LQT1 gene is , which has been isolated to chromosome 11p15.5. "KCNQ1" codes for the voltage-gated potassium channel KvLQT1 that is highly expressed in the heart. The product of the "KCNQ1" gene is thought to produce an alpha subunit that interacts with other proteins (in particular, the minK beta subunit) to create the I ion channel, which is responsible for the delayed potassium rectifier current of the cardiac action potential.
KvLQT1
Mutations in the gene can lead to a defective protein and several forms of inherited arrhythmias as Long QT syndrome which is a prolongation of the QT interval of heart repolarization, Short QT syndrome, and Familial Atrial Fibrillation. KvLQT1 are also expressed in the pancreas, and KvLQT1 Long QT syndrome patients has been shown to have hyperinsulinemic hypoglycaemia following an oral glucose load. Currents arising from K7.1 in over-expression systems have never been recapitulated in native tissues - K7.1 is always found in native tissues with a modulatory subunit. In cardiac tissue, these subunits comprise KCNE1 and yotiao. Though physiologically irrelevant, homotetrameric K7.1 channels also display a unique form of C-type inactivation that reaches equilibrium quickly, allowing KvLQT1 currents to plateau. This is different from the inactivation seen in A-type currents, which causes rapid current decay.KvLQT1 has been shown to interact with PRKACA, PPP1CA and AKAP9.
Norfloxacin
FQs prolong the QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.
Short QT syndrome
Short QT syndrome is diagnosed primarily using an electrocardiogram (ECG), but may also take into account the clinical history, family history, and possibly genetic testing. Whilst a diagnostic scoring system has been proposed that incorporate all of these factors (the Gollob score), it is uncertain whether this score is useful for diagnosis or risk stratification, and the Gollob score has not been universally accepted by international consensus guidelines. There continues to be uncertainty regarding the precise QT interval cutoff that is should be used for diagnosis.
Levofloxacin
Levofloxacin may prolong the QT interval in some people, especially the elderly, and levofloxacin should not be used for people with a family history of Long QT syndrome, or who have long QT, chronic low potassium, it should not be prescribed with other drugs that prolong the QT interval.
Cushing's syndrome
Other signs include increased urination (and accompanying increased thirst), persistent high blood pressure (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) and insulin resistance (especially common with ACTH production outside the pituitary), leading to high blood sugar and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cortisol can also exhibit mineralocorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion) and hypernatremia (increased Na+ ions concentration in plasma). Furthermore, excessive cortisol may lead to gastrointestinal disturbances, opportunistic infections, and impaired wound healing related to cortisol's suppression of the immune and inflammatory responses. Osteoporosis is also an issue in Cushing's syndrome since osteoblast activity is inhibited. Additionally, Cushing's syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back. Cushing’s syndrome includes all the causes of increased cortisol leading to the diseased state. Cushing’s disease is a specific type of Cushing’s syndrome caused by a pituitary tumor leading to excessive production of ACTH (adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, producing the disease state. Cushing's disease due to excess ACTH may also result in hyperpigmentation. This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Alternatively, it is proposed that the high levels of ACTH, β-lipotropin, and γ-lipotropin, which contain weak MSH function, can act on the melanocortin 1 receptor. A variant of Cushing's disease can be caused by ectopic, i.e. extrapituitary, ACTH production from, for example, a small-cell lung cancer. When Cushing's syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops. While all Cushing’s disease gives Cushing’s syndrome, not all Cushing’s syndrome is due to Cushing’s disease.
Metabolic syndrome
Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). A dysfunctional HPA-axis causes high cortisol levels to circulate, which results in raising glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" osteoporosis. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to cardiovascular disease (CVD), type 2 diabetes and stroke. Psychosocial stress is also linked to heart disease.
Ascending cholangitis
Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system). Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm "Ascaris lumbricoides" and the liver flukes "Clonorchis sinensis", "Opisthorchis viverrini" and "Opisthorchis felineus". In people with AIDS, a large number of opportunistic organisms has been known to cause "AIDS cholangiopathy", but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.
CQT
CQT may refer to
Long QT syndrome
LQT5 is an autosomal-recessive, relatively uncommon form of LQTS. It involves mutations in the gene "KCNE1", which encodes for the potassium channel beta subunit MinK. In its rare homozygous forms, it can lead to Jervell and Lange-Nielsen syndrome.
SGK1
A gain-of-function mutation in SGK1, or serum and glucocorticoid-inducible kinase 1, can lead to a shortening of the QT interval, which represents the repolarization time of the cardiac cells after a cardiac muscle contraction action potential. SGK1 does this by interacting with the KvLQT1 channel in cardiac cells, stimulating this channel when it is complex with KCNE1. SGK1 stimulates the slow delayed rectifier potassium current through this channel by phosphorylating PIKfyve, which then makes PI(3,5)P2, which goes on to increase the RAB11-dependent insertion of the KvLQT1/KCNE1 channels into the plasma membrane of cardiac neurons. SGK1 phosphorylates PIKfyve, which results in regulated channel activity through RAB11-dependent exocytosis of these KvLQT1/KCNE1-containing vesicles. Stress-induced stimuli have been known to activate SGK1, which demonstrates how Long QT Syndrome is brought on by stressors to the body or to the heart itself. By increasing the insertion of KVLQT1/KCNE1 channels into the plasma membrane through an alteration of trafficking within the cell, SGK1 is able to enhance the slow delayed potassium rectifier current in the neurons.
Short QT syndrome
The rarity of short QT syndrome makes calculating prognosis accurately difficult. The risk of sudden cardiac death has been estimated at 0.8% per year, leading to a cumulative risk of sudden cardiac death of 41% by the age of 40. A previous history of cardiac arrest predicts a higher likelihood of further dangerous arrhythmias. Some have suggested that those with the shortest QT intervals may have a higher risk of arrhythmias, but this view has not been supported by all. The findings from invasive electrophysiological studies do not predict an individual with short QT syndrome's risk of cardiac arrest.
BmTx3
When injected into mice it causes epileptiform behavior. This might be due to its effect on A-type K channels, which, like the Kv4.x, are involved in action potential back propagation, firing frequency, spike initiation and action potential waveform determination.
Blocking of the hERG channel can cause drug-induced long QT syndrome, arrhythmias and ventricular fibrillation which can result in death.
Louis Ptáček
His current research mainly focuses on identifying the genes involved with Andersen-Tawil syndrome (ATS). Ptáček's lab have identified KCNJ2 mutations to be potentially responsible for this syndrome, but due to the intrafamilial variability among the mutations, they hope to identify and characterize this gene further. Thus far, Ptáček and his colleagues have identified six disease-causing mutations, five of which are dominant negative mutations that mask the wild-type allele, resulting in a loss-of-function of that gene. With his continued research on ATS, Ptáček has discovered and identified additional phenotypic diagnostic criteria for ATS using skeletal and dental findings. Additionally, he has identified other markers of the KCNJ2 channel mutation's including its ECG outputs' T-Wave and U-Wave patterns in order to provide more accurate differential diagnosis from Long QT Syndrome.
Alivecor
The company is conducting research with Columbia University and the Mayo Clinic to determine if the KardiaBand can identify early warning signs of Long QT syndrome, a cause of sudden death, especially in young people.
Antillatoxin
Antillatoxin (ATX) is a potent lipopeptide neurotoxin produced by the marine cyanobacterium "Lyngbya majuscula". ATX activates voltage-gated sodium channels, which can cause cell depolarisation, NMDA-receptor overactivity, excess calcium influx and neuronal necrosis.
Ofloxacin
FQs prolong the QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.
Long-chain-fatty-acid—CoA ligase
Adrenoleukodystrophy (ALD), is the build up of long chain fatty acids in the brain and adrenal cortex, because of the decreased activity of long chain fatty acyl coa synthetase. The oxidation of the long chain fatty acids normally occurs in the peroxisome where the long chain fatty acyl coa synthetase is found. Long chain fatty acids enter the peroxisome via a transporter protein, ALDP, which creates a gate in the membrane of the peroxisome. In ALD the gene for this peroximal membrane transporter, ALDP, is defective, preventing long chain fatty acids from entering the peroxisome.
Short QT syndrome
The second mechanism relates to the increased number of fibrillatory wavelets that can simultaneously exist if the action potential decreases, in a concept known as the arrhythmia wavelength. During fibrillation, the chaotic wavelets rotate, or re-enter, within the muscle of the heart, continually extinguishing and reforming. The volume of tissue in which each wavelet can complete a re-entrant circuit is dependent on the refractory period of the tissue and the speed at which the waves of depolarisation traverse move – the conduction velocity. The product of the conduction velocity and refractory period is known as the wavelength. In tissue with a lower wavelength a wavelet can re-enter within a smaller volume of tissue. A shorter refractory period therefore allows more wavelets to exist within a given volume of tissue, reducing the chance of all wavelets simultaneously extinguishing and terminating the arrhythmia.
Heart arrhythmia
Causes of SADS in young people include viral myocarditis, long QT syndrome, Brugada syndrome, Catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia.
Ataxia
Exogenous substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is ethanol (alcohol), which is capable of causing reversible cerebellar and vestibular ataxia. Other examples include various prescription drugs (e.g. most antiepileptic drugs have cerebellar ataxia as a possible adverse effect), Lithium level over 1.5mEq/L, synthetic cannabinoid HU-211 ingestion and various other recreational drugs (e.g. ketamine, PCP or dextromethorphan, all of which are NMDA receptor antagonists that produce a dissociative state at high doses). A further class of pharmaceuticals which can cause short term ataxia, especially in high doses are the benzodiazepines. Exposure to high levels of methylmercury, through consumption of fish with high mercury concentrations, is also a known cause of ataxia and other neurological disorders.
Cardiac arrest
Examples of arrhythmic syndromes associated with SCD include: Long QT syndrome, Wolff-Parkinson-White Syndrome, Brugada Syndrome, Catecholaminergic polymorphic ventricular tachycardia.
Long QT syndrome
Those diagnosed with LQTS are usually advised to avoid drugs that would prolong the QT interval further or lower the threshold for TDP. In addition to this, two intervention options are known for individuals with LQTS: arrhythmia prevention and arrhythmia termination.
Tricyclic antidepressant
The TCAs are highly metabolised by the cytochrome P450 hepatic enzymes. Drugs that inhibit cytochrome P450 (for example cimetidine, methylphenidate, fluoxetine, antipsychotics, and calcium channel blockers) may produce decreases in the TCAs' metabolism, leading to increases in their blood concentrations and accompanying toxicity. Drugs that prolong the QT interval including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, and some antipsychotics may increase the chance of ventricular dysrhythmias. TCAs may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Side effects may also be enhanced by other drugs that have antimuscarinic properties.
QT interval
Prolongation of the QT interval may be due to an adverse drug reaction. Many drugs, such as haloperidol, vemurafenib, ziprasidone, methadone and sertindole, can prolong the QT interval. Some antiarrhythmic drugs, like amiodarone or sotalol, work by getting a pharmacological QT prolongation. Also, some second-generation antihistamines, such as astemizole, have this effect. In addition, high blood alcohol concentrations prolong the QT interval. A possible interaction between selective serotonin reuptake inhibitors and thiazide diuretics is associated with QT prolongation. Macrolide and fluoroquinolone antibiotics are also suspected to prolong the QT interval. It was discovered recently that azithromycin is associated with an increase in cardiovascular death.
Delayed ejaculation
Medical conditions that can cause delayed ejaculation include hypogonadism, thyroid disorders, pituitary disorders such as Cushing's disease, prostate surgery outcome, and drug and alcohol use. Difficulty in achieving orgasm can also result from pelvic surgery that involved trauma to pelvic nerves responsible for orgasm. Some men report a lack of sensation in the nerves of the glans penis, which may or may not be related to external factors, including a history of circumcision.
Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Mutations in the "HADHA" gene lead to inadequate levels of an enzyme called long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, which is part of a protein complex known as mitochondrial trifunctional protein. Long-chain fatty acids from food and body fat cannot be metabolized and processed without sufficient levels of this enzyme. As a result, these fatty acids are not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, retina, and muscles, causing more serious complications.
Catecholaminergic polymorphic ventricular tachycardia
The resting 12-lead ECG is a useful test to differentiate CPVT from other electrical diseases of the heart that can cause similar abnormal heart rhythms. Unlike conditions such as long QT syndrome and Brugada syndrome, the resting 12-lead ECG in those with CPVT is generally normal. However, approximately 20% of those affected have a slow resting heart rate or sinus bradycardia.
Hypertension
Secondary hypertension results from an identifiable cause. Kidney disease is the most common secondary cause of hypertension. Hypertension can also be caused by endocrine conditions, such as Cushing's syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conn's syndrome or hyperaldosteronism, renal artery stenosis (from atherosclerosis or fibromuscular dysplasia), hyperparathyroidism, and pheochromocytoma. Other causes of secondary hypertension include obesity, sleep apnea, pregnancy, coarctation of the aorta, excessive eating of liquorice, excessive drinking of alcohol, and certain prescription medicines, herbal remedies, and illegal drugs such as cocaine and methamphetamine. Arsenic exposure through drinking water has been shown to correlate with elevated blood pressure.
QT interval
Prolonged QTc causes premature action potentials during the late phases of depolarization. This increases the risk of developing ventricular arrhythmias, including fatal ventricular fibrillation. Higher rates of prolonged QTc are seen in females, older patients, high systolic blood pressure or heart rate, and short stature. Prolonged QTc is also associated with EKG findings called Torsades de Pointes, which are known to degenerate into ventricular fibrillation, associated with higher mortality rates. There are many causes of prolonged QT intervals, acquired causes being more common than genetic.
Short QT syndrome
Short QT syndrome is a genetic disorder caused by mutations in genes responsible for producing certain ion channels within heart cells. It appears to be inherited in an autosomal dominant pattern. Some genetic variants cause an increased flow of potassium out of the cell, while others reduce the flow of calcium into the cell. The common effect of all these variants is to shorten the cardiac action potential, reflected on the surface ECG as a shortening of the QT interval. A list of genes in which variants have been associated with short QT syndrome can be found in the table below.
The overall effect of each of the genetic variants associated with short QT syndrome is to shorten the cardiac action potential, which in turn increases the risk of developing abnormal heart rhythms including atrial fibrillation and ventricular fibrillation. During the normal rhythm of the heart, or sinus rhythm, smooth waves of electrical activity pass regularly through the cardiac muscle. In contrast, during atrial or ventricular fibrillation, waves of electrical activation spiral through the cardiac muscle chaotically in a mass of disorganised, broken wavelets. The consequence of fibrillation is that the chambers of the heart affected by the disorganised electrical activation lose their pumping ability – fibrillation of the cardiac atria in atrial fibrillation leads to an irregular pulse, and fibrillation of the cardiac ventricles in ventricular fibrillation renders the heart unable to pump blood at all.
Short QT syndrome
Drugs can also be used to treat the less dangerous abnormal heart rhythm that is also associated with short QT – atrial fibrillation. Propafenone, a class 1c antiarrhythmic, may be helpful in those with short QT to prevent atrial fibrillation. Those who develop atrial fibrillation may also require medication to decrease blood clotting in order to reduce the risk of stroke.
Long QT syndrome
Arrhythmia suppression involves the use of medications or surgical procedures that attack the underlying cause of the arrhythmias associated with LQTS. Since the cause of arrhythmias in LQTS is EADs, and they are increased in states of adrenergic stimulation, steps can be taken to blunt adrenergic stimulation in these individuals. These include administration of beta receptor blocking agents, which decreases the risk of stress-induced arrhythmias. Beta blockers are an effective treatment for LQTS caused by LQT1 and LQT2.
Long-term depression
The mechanisms of LTD differ in the two subregions of the striatum. LTD is induced at corticostriatal medium spiny neuron synapses in the dorsal striatum by a high frequency stimulus coupled with postsynaptic depolarization, coactivation of dopamine D1 and D2 receptors and group I mGlu receptors, lack of NMDA receptor activation, and endocannabinoid activation.
Short QT syndrome
In those with short QT syndrome who have already experienced a life-threatening abnormal heart rhythm such as ventricular fibrillation, an implantable cardioverter-defibrillator (ICD) may be recommended to reduce the chance of sudden death. This device is implanted under the skin and can continually monitor the heart rhythm. If the device detects a dangerous heart rhythm disturbance it can deliver a small electric shock with the aim of restoring a rhythm. Implanting an ICD in someone with short QT syndrome who has not yet experienced a life-threatening arrhythmia is more controversial but may be considered.
Acute fatty liver of pregnancy
The understanding of the causes of acute fatty liver of pregnancy 
has been improved by advances in mitochondrial biochemistry. Deficiency of LCHAD (3-hydroxyacyl-CoA dehydrogenase) leads to an accumulation of medium and long chain fatty acids. When this occurs in the foetus, the unmetabolized fatty acids will re-enter the maternal circulation through the placenta, and overwhelm the beta-oxidation enzymes of the mother. The gene responsible for LCHAD has been isolated, and the most common mutation found in acute fatty liver of pregnancy is the E474Q missense mutation. LCHAD deficiency is autosomal recessive in inheritance and mothers are often found to be heterozygous for the affected mutation.
Potassium channel
Medically potassium channel blockers, such as 4-aminopyridine and 3,4-diaminopyridine, have been investigated for the treatment of conditions such as multiple sclerosis. Off target drug effects can lead to drug induced Long QT syndrome, a potentially life-threatening condition. This is most frequently due to action on the hERG potassium channel in the heart. Accordingly, all new drugs are preclinically tested for cardiac safety.
Long QT syndrome
Andersen-Tawil syndrome is an autosomal-dominant form of LQTS associated with skeletal deformities. It involves mutation in the gene "KCNJ2", which encodes for the potassium channel protein Kir 2.1. The syndrome is characterized by LQTS with ventricular arrhythmias, periodic paralysis, and skeletal developmental abnormalities such as clinodactyly, low-set ears, and micrognathia. The manifestations are highly variable.Timothy syndrome is due to mutations in the calcium channel Cav1.2 encoded by the gene "CACNA1c". Since the calcium channel Cav1.2 is abundant in many tissues, patients with Timothy syndrome have many clinical manifestations, including other congenital heart disease, autism, immune deficiency and complex syndactyly.
PRKACA
Protein kinase A has been implicated in a number of diseases, including cardiovascular disease, tumors of the adrenal cortex, and cancer. It has been speculated that abnormally high levels of PKA phosphorylation contributes to heart disease. This affects excitation-contraction coupling, which is a rhythmic process that controls the contraction of cardiac muscle through the synchronized actions of calcium and cAMP responsive enzymes. There is also evidence to support that the mis-localization of PKA signaling contributes to cardiac arrhythmias, specifically Long QT syndrome. This results in irregular heartbeats that can cause sudden death.
KCNE1
While loss-of-function mutations in KCNE1 cause Long QT syndrome, gain-of-function KCNE1 mutations are associated with early-onset atrial fibrillation. A common KCNE1 polymorphism, S38G, is associated with altered predisposition to lone atrial fibrillation and postoperative atrial fibrillation. Atrial KCNE1 expression was downregulated in a porcine model of post-operative atrial fibrillation following lung lobectomy.
Long-term depression
In the prelimbic cortex of the striatum, three forms or LTD have been established. The mechanism of the first is similar to CA1-LTD: a low frequency stimulus induces LTD by activation of NMDA receptors, with postsynaptic depolarization and increased postsynaptic calcium influx. The second is initiated by a high frequency stimulus and is arbitrated by presynaptic mGlu receptor 2 or 3, resulting in a long term reduction in the involvement of P/Q-type calcium channels in glutamate release. The third form of LTD requires endocannabinoids, activation of mGlu receptors and repetitive stimulation of glutamatergic fibers (13 Hz for ten minutes), resulting in a long term decrease in presynaptic glutamate release. It is proposed that LTD in GABAergic striatal neurons leads to a long term decrease in inhibitory effects on the basal ganglia, influencing the storage of motor skills.
Long QT syndrome
There are several subtypes of long QT syndrome. These can be broadly split into those caused by genetic mutations which those affected are born with, carry throughout their lives, and can pass on to their children (inherited or congenital long QT syndrome), and those caused by other factors which cannot be passed on and are often reversible (acquired long QT syndrome).
ANK2
Initially, a Glu1425Gly mutation in "ANK2" was found to cause dominantly-inherited long QT syndrome, type 4, cardiac arrhythmia. The mechanistic underpinnings of this mutation include abnormal expression and targeting of the sodium pump, the sodium-calcium exchanger, and inositol-1,4,5-trisphosphate receptors to transverse tubules, as well as calcium handling resulting in extrasystoles. Further analysis in "ANK2" mutations localized in the regulatory domain of ankyrin-2, which is specific to the ankyrin-2 isoform, indicated that long QT syndrome was not a consistent clinical manifestation of "ANK2" mutations; however, the effect on Ca(2+) dynamics and localization/expression of the sodium calcium exchanger, sodium potassium ATPase and inositol triphosphate receptor in cardiomyocytes were consistent observations. This study demonstrated that common pathogenic features of all "ANK2" mutations was the abnormal coordination of a panel of related ion channels and transporters. Additional mechanistic studies have shown that atrial cardiomyocytes lacking ankyrin-B have shortened action potentials, which can be explained by decreased voltage-dependent calcium channel expression, specifically Ca(v)1.3, which is responsible for low voltage-activated L-type Ca(2+) currents. Ankyrin-B directly associates with and is required for targeting Ca(v)1.3 to membranes.
Drug-induced QT prolongation
Drug-induced QT prolongation is seen with a QT interval above 450 ms on the ECG and is usually a result of treatment by anti-arrhythmic drugs, such as amiodarone and sotalol, or a number of other drugs that have been reported to cause this problem (e.g., cisapride). Some antipsychotic drugs, such as haloperidol and ziprasidone, have a prolonged QT interval as a rare side-effect. Antihistamines, erythromycin, and ciprofloxacin may also cause drug-induced LQT. Genetic mutations may make one more susceptible to drug-induced LQT. It is associated with hypokalaemia, hypocalcaemia and hypothermia and may lead to torsades de pointes.
Quantitative tightening
Whereas QE caused the substantial rise in asset prices over the past decade, QT may cause broadly offsetting effects in the opposite direction.
Nav1.5
Mutations resulting in a gain-of-function are causal for Long QT syndrome type 3 and are also more recently implicated in multifocal ectopic Purkinje-related premature contractions (MEPPC) Some gain-of-function mutations are also associated with AF and DCM. Gain-of-function of Na1.5 is generally reflected by an increase in I, a slowed rate of inactivation or a shift in voltage dependence of activation or inactivation (resulting in an increased window-current).
Stellate ganglion
Left stellectomy is a treatment strategy in prolonged QT syndrome because it drives prolonged QT, but only in patients who are already on a beta blocker and experience frequent shocks from an ICD, because stellectomy causes Horner's syndrome.
Cav1.2
Mutation in the CACNA1C gene, the single-nucleotide polymorphism located in the third intron of the Cav1.2 gene, are associated with a variant of Long QT syndrome called Timothy's syndrome and also with Brugada syndrome. Large-scale genetic analyses have shown the possibility that CACNA1C is associated with bipolar disorder and subsequently also with schizophrenia. Also, a CACNA1C risk allele has been associated to a disruption in brain connectivity in patients with bipolar disorder, while not or only to a minor degree, in their unaffected relatives or healthy controls.
Quinolone antibiotic
Fluoroquinolones prolong the heart's QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.
Ventricular tachycardia
Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems (e.g., low blood levels of magnesium or potassium), inherited channelopathies (e.g., long-QT syndrome), catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, or a heart attack.
Long-term depression
Long-term depression has also been observed in the visual cortex, and it is proposed to be involved in ocular dominance. Recurring low-frequency stimulation of layer IV of the visual cortex or the white matter of the visual cortex causes LTD in layer III. In this form of LTD, low-frequency stimulation of one pathway results in LTD only for that input, making it homosynaptic. This type of LTD is similar to that found in the hippocampus, because it is triggered by a small elevation in postsynaptic calcium ions and activation of phosphatases. LTD has also been found to occur in this fashion in layer II. A different mechanism is at work in the LTD that occurs in layer V. In layer V, LTD requires low frequency stimulation, endocannabinoid signaling, and activation of presynaptic NR2B-containing NMDA receptors.
Short QT syndrome
The first report of short QT syndrome to be published was in 2000, describing a family with short QT intervals on the 12-lead ECG, atrial fibrillation occurring at a young age, and an unrelated patient who suffered sudden cardiac death associated with a short QT interval. The association between short QT and sudden cardiac death was described in 2003, and the first gene associated with the condition was identified in 2004. Criteria for diagnosing Short QT syndrome were proposed in 2011.
Carnitine-acylcarnitine translocase deficiency
Without this enzyme, long-chain fatty acids from food and fats stored in the body cannot be broken down and processed. As a result, these fatty acids are not converted into energy, which can lead to characteristic signs and symptoms of this disorder, such as weakness, hypoglycemia, and an irregular heartbeat. Free long-chain fatty acids or those that are joined with carnitine can affect the electrical properties of cardiac cells causing an irregular heart beat (arrhythmia, which can lead to cardiac arrest). Fatty acids may also build up in tissues and can damage the heart, liver, and muscles, and cause more serious complications.
Torsades de pointes
Common causes for torsades de pointes include diarrhea, low blood magnesium, and low blood potassium. It is commonly seen in malnourished individuals and chronic alcoholics, due to a deficiency in potassium and/or magnesium. Certain combinations of drugs resulting in drug interactions can contribute to torsades de pointes risk. QT prolonging medications such as clarithromycin, levofloxacin, or haloperidol, when taken concurrently with cytochrome P450 inhibitors, such as fluoxetine, cimetidine, or particular foods including grapefruit, can result in higher-than-normal levels of medications that prolong the QT interval in the bloodstream and therefore increase a person's risk of developing torsades de pointes. In addition, inherited long QT syndrome significantly increases the risk of episodes of TdP.
Amiodarone
It also shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. It is suggested that amiodarone may also exacerbate the phenotype associated with Long QT-3 syndrome causing mutations such as ∆KPQ. This effect is due to a combination of blocking the peak sodium current, but also contributing to an increased persistent sodium current.
Long QT syndrome
While those with long QT syndrome have an increased risk of developing abnormal heart rhythms compared to those without the condition, the absolute risk of arrhythmias is very variable. The strongest predictor of whether someone will develop torsades de pointes (TdP) is whether they have experienced spontaneous TdP or another form of cardiac arrest in the past. Even if an arrhythmia has not been witnessed, a person with LQTS who has experienced syncope is also at higher risk, as syncope in these cases is frequently due to an undocumented self-terminating arrhythmia.
Long QT syndrome
The first documented case of LQTS was described in Leipzig by Meissner in 1856, when a deaf girl died after her teacher yelled at her. When the parents were notified of her death, they reported that her older brother, who also was deaf, died after a terrible fright. This was several decades before the ECG was invented, but is likely the first described case of Jervell and Lange-Nielsen syndrome. In 1957, the first case documented by ECG was described by Anton Jervell and Fred Lange-Nielsen, working in Tønsberg, Norway. Italian pediatrician Cesarino Romano, in 1963, and Irish pediatrician Owen Conor Ward, in 1964, separately described the more common variant of LQTS with normal hearing, later called Romano-Ward syndrome. The establishment of the International Long-QT Syndrome Registry in 1979 allowed numerous pedigrees to be evaluated in a comprehensive manner. This helped in detecting many of the numerous genes involved.
Clarithromycin
Clarithromycin can lead to a prolonged QT interval. In patients with long QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threatening arrhythmias.
Rett syndrome
Because of the increased risk of sudden cardiac death, when long QT syndrome is found on an annual screening EKG it is treated with an anti-arrhythmic such as a beta-blocker. There is some evidence that phenytoin may be more effective than a beta-blocker.
Ventricular tachycardia
Polymorphic ventricular tachycardia, on the other hand, is most commonly caused by abnormalities of ventricular muscle repolarization. The predisposition to this problem usually manifests on the ECG as a prolongation of the QT interval. QT prolongation may be congenital or acquired. Congenital problems include long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Acquired problems are usually related to drug toxicity or electrolyte abnormalities, but can occur as a result of myocardial ischemia. Class III anti-arrhythmic drugs such as sotalol and amiodarone prolong the QT interval and may in some circumstances be pro-arrhythmic. Other relatively common drugs including some antibiotics and antihistamines may also be a danger, in particular in combination with one another. Problems with blood levels of potassium, magnesium and calcium may also contribute. High-dose magnesium is often used as an antidote in cardiac arrest protocols.
Short QT syndrome
Short QT syndrome (SQT) is a very rare genetic disease of the electrical system of the heart, and is associated with an increased risk of abnormal heart rhythms and sudden cardiac death. The syndrome gets its name from a characteristic feature seen on an electrocardiogram (ECG) – a shortening of the QT interval. It is caused by mutations in genes encoding ion channels that shorten the cardiac action potential, and appears to be inherited in an autosomal dominant pattern. The condition is diagnosed using a 12-lead ECG. Short QT syndrome can be treated using an implantable cardioverter-defibrillator or medications including quinidine. Short QT syndrome was first described in 2000, and the first genetic mutation associated with the condition was identified in 2004.
Glycation
Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as crystallins of the lens and cornea), and DNA may accumulate substantial damage over time. Cells such as the retina cells in the eyes, and beta cells (insulin-producing) in the pancreas are also at high risk of damage. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurisms; this may cause strokes if in the brain.
Loss of tail-rotor effectiveness
Environmental factors which can lead to LTE include higher operating-density altitudes or temperatures, and high winds. A high gross weight can also create an LTE-conducive situation. Causative wind-directions may include:Many factors affect the onset of LTE, but no matter which way it occurs, the clues are present:
Sudden arrhythmic death syndrome
A sudden death in a young person can be caused by heart disease (including cardiomyopathy, congenital heart disease, myocarditis, genetic connective tissue disorders, or conduction disease), medication-related causes or other causes. Rare diseases called channelopathies may play a role such as long QT syndrome (LQTS), Brugada syndrome (BrS), CPVT (catecholaminergic polymorphic ventricular tachycardia), PCCD (progressive cardiac conduction defect), early repolarisation syndrome, mixed sodium channel disease, and short QT syndrome. No cause of death is found, even after extensive examination in 5% of cases.