why does digoxin shorten qt interval

The ECG

features of digoxin effect are seen with therapeutic doses of digoxin and are due to: Shortening of the atrial and ventricular refractory periods — producing a short QT interval with secondary repolarisation abnormalities affecting the ST segments, T waves and U waves Increased vagal effects at the AV node — causing a prolonged PR interval

Full Answer

What are the ECG features of digoxin effect?

The ECG features of digoxin effect are seen with therapeutic doses of digoxin and are due to: Shortening of the atrial and ventricular refractory periods — producing a short QT interval with secondary repolarisation abnormalities affecting the ST segments, T waves and U waves Increased vagal effects at the AV node — causing a prolonged PR interval

Do drugs shorten QT intervals?

Drugs as a cause of QT interval shortening There is no denying that at present, there is a substantial gap between the existing evidence linking drug-induced QT prolongation to numerous treatment-related fatalities and the less well-documented potential risks and outcomes associated with drug-induced QT shortening.

What is proarrhythmic shortening of Qt?

As with QT prolongation, proarrhythmic shortening of QT interval is also associated with an increase in transmural dispersion of repolarization, a parameter believed to be a better marker of proarrhythmic risk (Antzelevitch and Oliva, 2006; Anttonen et al., 2008). Drugs as a cause of QT interval shortening

What arrhythmias are not caused by digoxin?

The arrhythmias/conduction defects that are not caused by digoxin are as follows: second-degree AV block type 2, atrial flutter, bundle branch block. One should be particularly suspicious if there is evidence of increased automaticity and simultaneous diminished impulse conduction (e.g AV block).

Why does digoxin cause QT shortening?

Digoxin's primary mechanism of action is thought to result from increased intracellular Ca2+ concentration due to inhibition of the sodium-potassium ATPase, with resultant increased ventricular contraction, followed by a shortened ventricular refractory period with QT-interval shortening on electrocardiogram (ECG) [1, ...

How does digoxin affect QT interval?

Digoxin treatment also increases [Ca2+]i but shortens QT (via vagal activation). It predisposes to TdP [3, 4], presumably through this mechanism, as well as by causing bradycardia.

Does digoxin cause QT prolongation?

Recipients of digoxin also may be at higher risk of torsades de pointes, although digoxin itself does not prolong the QT interval. Epidemiological research con- sistently shows an increased risk of drug-induced torsades de pointes in women, who have longer QT intervals in the absence of drug therapy.

Why does digoxin prolong PR interval?

Digoxin enhances Vagus nerve activity, which slows conduction over the AV node. Digoxin also has a direct effect on AV conduction, by slowing it. This causes prolongation of the PR interval, which is considered a normal finding, unless severely prolonged.

What is the mechanism of action of digoxin?

Mechanism of action Digoxin binds to and inhibits the sodium/potassium-ATPase (sodium pump) within the plasma membrane of cardiac myocytes. This inhibition increases the intracellular sodium content which in turn increases the intracellular calcium content which leads to increased cardiac contractility.

How does digoxin cause Dysrhythmias?

Digoxin can cause a multitude of dysrhythmias due to: Increased automaticity (increased intracellular calcium) Decreased AV conduction (increased vagal effects at the AV node)

How does digoxin effect ECG?

The ECG features of digoxin effect are seen with therapeutic doses of digoxin and are due to: Shortening of the atrial and ventricular refractory periods — producing a short QT interval with secondary repolarisation abnormalities affecting the ST segments, T waves and U waves.

How does digoxin cause heart block?

Pathophysiology – Digoxin Toxicity Digoxin blocks the sodium/potassium ATPase pump. The mechanism by which this decreases AV conduction is not clear but is perhaps due to increased vagal tone. Intracellular calcium within the cardiac myocytes is increased by digoxin, resulting in increased inotropy, or contractility.

What drugs shorten QT interval?

Beta blockers used to treat long QT syndrome include nadolol (Corgard) and propranolol (Inderal LA, InnoPran XL). Mexiletine. Taking this heart rhythm drug with a beta blocker might help shorten the QT interval and reduce the risk of fainting, seizure or sudden death.

Is digoxin a vasodilator or vasoconstrictor?

In conclusion, digoxin produces a pulmonary vasoconstriction through an alpha-adrenergic mechanism. Since the pressor response was observed only in the blood-perfused lung, blood-borne catecholamines are apparently involved.

Why is digoxin not used in ventricular tachycardia?

The use of digoxin is contraindicated in patients with ventricular fibrillation. Digoxin toxicity is associated with adverse cardiac effects, including ventricular arrhythmias, which are most commonly seen in chronic toxicity.

Why is digoxin used in atrial fibrillation?

Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. In the last two decades, several studies have correlated therapeutic use of digoxin with increased mortality.

What medication causes prolonged QT interval?

A long QT interval is most frequently seen with class I and class III antiarrhythmic drugs. Other classes of drugs that cause QTc prolongation include antihistamines, antidepressants, antibiotics, antifungal drugs and antipsychotics (Table 2).

What can cause prolonged QT interval?

Long QT syndrome is usually caused by a faulty gene inherited from a parent. The abnormal gene affects the heart's electrical activity. Certain medicines can also trigger long QT syndrome, including some types of: antibiotics.

What medications affect QT interval?

Drugs Causing QT ProlongationChlorpromazine.Haloperidol.Droperidol.Quetiapine.Olanzapine.Amisulpride.Thioridazine.

What medications cause QT prolongation?

The most potent QT-prolonging medications are antiarrhythmic agents, particularly amiodarone, dofetilide, quinidine, and sotalol, with quinidine possibly having the most torsadogenic potential.

What are the changes in EKG due to digoxin?

Changes in the EKG due to digoxin: ST depression in a concave shape, known as a " reverse tick sign " or as " Salvador Dali sagging sign ". Flat, negative or biphasic T waves. Depression of J point. Short QT interval. Prolonged PR interval (secondary to increased vagal tone). Prominent U waves. Terminal portion of the pointed T wave.

How long does it take for digoxin to be detected?

Treatment of Digoxin Toxicity. When high serum levels of digoxin are detected in the absence of symptoms, whether the analytical test was performed within 6 hours of the last dose of digoxin must be verified, as that may be the cause of high analytical values.

What are the most common cardiac manifestations of digoxin toxicity?

The most frequent are the premature ventricular complexes, AV junction extrasystoles or atrial fibrillation with excessively slow ventricular response 6.

What is reverse tick on electrocardiogram?

Reverse tick on the electrocardiogram: The ST has a morphology similar to a reverse tick, it also helps to remember that the digoxin pill fits in the ST depression. The depression of the ST segment makes one think of the mustache of the famous painter.

What is the main indication for digoxin?

Currently, the main indication for the use of digoxin is the control of heart rate in patients with atrial fibrillation and heart failure 3 4 5. It can also be used in patients in sinus rhythm with symptomatic heart failure and ejection fraction ≤40% 5. Digoxin inhibits the sodium-potassium ATPase pump, causing increased vagal tone ...

What is the sign of digoxin?

The classic electrocardiographic sign of digoxin treatment is the so-called “reverse tick” sign which is no more than the ST segment depression in a concave shape. It also has received other names like “hockey stick”, or “Salvador Dalí's mustache”, because it has a similar shape. Reverse tick on the electrocardiogram.

What are the changes in EKG?

Changes in the EKG due to digoxin: 1 ST depression in a concave shape, known as a " reverse tick sign " or as " Salvador Dali sagging sign ". 2 Flat, negative or biphasic T waves. 3 Depression of J point. 4 Short QT interval. 5 Prolonged PR interval (secondary to increased vagal tone). 6 Prominent U waves. 7 Terminal portion of the pointed T wave.

Which arrhythmias are not caused by digoxin?

The arrhythmias/conduction defects that are not caused by digoxin are as follows: second-degree AV block type 2, atrial flutter, bundle branch block. One should be particularly suspicious if there is evidence of increased automaticity and simultaneous diminished impulse conduction (e.g AV block).

What happens if you overdose on digoxin?

The typical patient with digoxin overdose will present with extrasystoles (premature beats) and various degrees of AV block.

Is digoxin a risk factor for arrhythmia?

Thus, digoxin is rather unpredictable in terms of arrhythmia risk.

Does digoxin increase automaticity?

This increases the automaticity in cells with natural automaticity but it may also provoke abnormal automaticity in cells that normally do not exhibit automaticity. The effect on automaticity should be distinguished from the effect on impulse conduction, because digoxin slows impulse conduction. It is important to note that ...

Does digoxin cause abnormality?

This is explained by the increase in intracellular calcium levels, which causes a shortening of the action potential. Digoxin shortens the action potential in all cardiac cells, both in the atria and the ventricles. This increases the automaticity in cells with natural automaticity but it may also provoke abnormal automaticity in cells that normally do not exhibit automaticity. The effect on automaticity should be distinguished from the effect on impulse conduction, because digoxin slows impulse conduction.

Is digoxin safe for heart failure?

Digoxin may be used in patients with heart failure, atrial fibrillation, atrial flutter and in selected cases of paroxysmal supraventricular tachycardia. Due to its profound pro-arrhythmic effects and lack of compelling data regarding morbidity and mortality benefit, digoxin has been expelled repeatedly from the treatment arsenal. However, it has kept coming back and it is still used in patients who do not achieve satisfactory effect by first line therapies. Moreover, digoxin is used frequently in the emergency setting to slow ventricular rate during supraventricular tachycardia (e.g atrial fibrillation ). Because digoxin may cause life-threatening arrhythmias, every health care provider must be able to recognize common digoxin ECG changes and arrhythmias.

Is digoxin an overdose?

Hence, arrhythmias may occur in the absence of ECG changes and vice versa (i.e ECG changes may be pronounced without any arrhythmias occurring). Plasma levels >2 ng/mL are considered an overdose. However, arrhythmia may occur at plasma levels below 2 ng/mL and arrhythmias may not occur even at higher plasma levels. Thus, digoxin is rather unpredictable in terms of arrhythmia risk.

What is Digoxin?

Digoxin has active ingredients of digoxin. It is often used in atrial fibrillation/flutter. eHealthMe is studying from 86,670 Digoxin users for its effectiveness, alternative drugs and more.

What is phase IV of Digoxin?

The phase IV clinical study analyzes which people take Digoxin and have Long qt syndrome. It is created by eHealthMe based on reports of 81,905 people who have side effects when taking Digoxin from the FDA, and is updated regularly. Running one of the largest drug safety studies in the world, eHealthMe is able to enable everyone to run personal ...

What drugs prolong QT interval?

Until 1964, quinidine and thioridazine were the only two widely used drugs known to prolong QTc interval and induce ventricular tachyarrhythmias. With time and increased awareness, a vast number of other non-cardiac drugs have now come to be associated with QT interval prolongation. A brief chronology of drug classes later shown to have the potential to prolong QT interval and induce TdP has been reviewed previously (Shah, 2007). The first entire drug class to be associated with QT liability were the neuroleptic drugs. Indeed, some of these neuroleptics were sufficiently potent in their QT prolonging (class III antiarrhythmic) activity and such was the faith in QT interval prolongation as an efficient antiarrhythmic mechanism that at one time, melperone (a butyrophenone neuroleptic) was being investigated for its use as an antiarrhythmic agent (Mogelvang et al., 1980; Smiseth et al., 1981). The number of torsadogenic drugs has continued to increase inexorably and at present, a large number of drugs from diverse therapeutic classes have been implicated in prolonging QT interval (de Ponti et al., 2001; 2002; Shah, 2002; 2007;). At the last count in April 2009, the author was able to compile a list (unpublished) of just over 160 drugs with clinical and/or strong non-clinical evidence of QT-prolonging effect.

What is the normal QTC interval?

According to Drew et al.(2004), a normal QTc interval is <450 ms in men and <460 ms in women. The Report from ACC/AHA/HRS on ‘Key Data Elements and Definitions for Electrophysiological Studies and Procedures’ defines the upper limit of QTc interval at 440 ms for adult men and 460 ms for adult women (Buxton et al., 2006). From a large dataset of ECGs of 46 129 individuals with a very low probability of cardiovascular disease and using the 2nd and 98th percentiles, Mason et al.(2007) have determined normal reference range to be 361–457 ms for QTcB interval and 359–445 ms for Fridericia-corrected QTc (QTcF) interval. On the basis of available data, the present author concludes that 360 ms is probably a reasonable value for the lower limit of normal QTcF interval.

What drugs are used to shorten the APD?

Drugs activating ATP-dependent potassium channel have been known for a long time (Escande et al., 1989). Among the better known are pinacidil , levcromakalim and nicorandil. There is evidence that pinacidil and levcromakalim induce shortening of APD and have profibrillatory effects in preclinical studies (de La Coussaye et al., 1993; Tosaki et al., 1993; Robert et al., 1997; Robert et al., 1999; Extramiana and Antzelevitch, 2004). Nicorandil has frequently been used in the treatment of patients with congenital LQTS (Chinushi et al., 1995; Shimizu and Antzelevitch, 2000). It has complex electrophysiological actions, but its effects are not potent enough to induce any proarrhythmic effect in angina patients with normal QT interval. Mallotoxin and NS1643 (both hERG current stimulators) and levcromakalim and nicorandil (neither having an effect on hERG current) have all been reported to significantly shorten APD and QT interval and elicit VF in isolated hearts (Lu et al., 2008). Nicorandil is already approved for the treatment of angina pectoris. During the period from November 1994 to November 2008, the UK regulatory authority (MHRA) had received a total of 1032 adverse event reports in association with nicorandil, of which six were reports of VF suspected to be associated with nicorandil (MHRA, 2008). However, the author has no information on the QTc intervals in these patients. As a matter of caution, therefore, drugs which are hERG stimulators or are without effect on hERG channel should also be tested for their effect on APD, QT interval and profibrillatory effects.

Why is the link between SQTS and VF difficult to interpret?

The link between SQTS and VF has been rendered difficult to interpret because of differences in definition of what constitutes a ‘short QT interval’. Because there are other factors that modulate the risk of proarrhythmia, it seems that the expectation of a sharp cut-off value for proarrhythmic shortening of QT interval may be unrealistic if the data on LQTS are anything to go by.

What is the QTC interval of K897T?

Bezzina et al.(2003) reported a significant association between K897T (A2690C), a common KCNH2amino acid polymorphism, and QTc interval in German White population. Subjects with CC genotype had significantly shorter QTc interval (388.5 ± 2.9 ms) compared with AA homozygotes (398.5 ± 0.9 ms) and AC heterozygotes (397.2 ± 1.2 ms). The CC genotype frequencies were 5.6% in male people and 5.1% in female people. Itoh et al.(2009) have also recently identified another KCNH2modifier mutation (R1135H) in a patient with short QT interval (QTc interval of 329 ms). It is not inconceivable that individuals who harbour these mutations may also be at a risk of substantial QT interval shortening when challenged with drugs that normally shorten QT interval only modestly.

Is QTC shorter in VF?

Viskin et al.(2004) have reported from a case–control study that despite a significant overlap, the QTc interval of male patients with idiopathic VF was shorter than the QTc interval of otherwise healthy male people (371 ± 22 ms vs. 385 ± 19 ms, P= 0.034). Short QT intervals were found more frequently among male patients with idiopathic VF (35% vs. 10%, P= 0.003). There was a gender effect with no such differences being apparent among women. The authors emphasize that none of the patients had QT interval values as short as those described in the SQTS.

Is LQT1 a heterogeneous syndrome?

Molecular studies much later established that genetically and clinically, congenital LQTS is a heterogeneous syndrome. At present, at least 12 variant forms have been formally designated as distinct entities (styled as LQT1 to LQT12). For a more detailed discussion on the complexities of the genetics of LQTS, the reader is referred to other reviews (Vincent, 2000; Priori et al., 2001; Roden, 2006; Schwartz, 2006; Crotti et al., 2008; Zareba and Cygankiewicz, 2008). Although patients with LQTS may experience a range of potentially fatal malignant ventricular tachyarrhythmias including ventricular fibrillation (VF), the prototype arrhythmia most frequently observed in these patients is torsade de pointes (TdP), a polymorphic ventricular tachycardia with a unique morphology on electrocardiogram (ECG). The arrhythmia may result in recurrent syncopes, seizure or sudden death. Depending on the LQTS genotype of the patient, other forms of rhythm disturbances observed include severe sinus bradycardia, paroxysmal atrial fibrillation (AF) and/or 2:1 functional atrioventricular block.

How often should you document QT interval?

Continue monitoring and documenting the QT interval at least once every 8 hours.

How to treat congenital LQTS?

If you take care of a patient newly diagnosed with congenital LQTS, patient education needs to be a priority. Teach the patient to prevent adrenergic surges in heart rhythm by avoiding loud noises, such as telephones, doorbells, and alarm clocks. The patient may need to turn down the doorbell and phone volume or turn the phone ringer off at night. Also teach the patient to avoid overexertion. Patients with confirmed LQTS1 or LQRS2 shouldn't participate in competitive sports . Tell the patient to seek medical attention if he or she has any illnesses that lower the potassium levels, such as vomiting or diarrhea, because this could trigger an episode of TdP. Ask the patient whether he or she has any family history of sudden cardiac arrest.

How did it get so long?

LQTS is a result of the heart's electrical system recharging abnormally. There are two types: acquired and congenital. Acquired LQTS is caused by an underlying medical condition, such as drugs that prolong the QT interval, electrolyte imbalances (such as caused by anorexia), and bradycardia. Congenital LQTS is inherited from one or both parents. In addition, there are 12 different subtypes of LQTS, labeled LQT1 to LQT12.

What is LQTS in medical terms?

LQTS is a result of the heart's electrical system recharging abnormally. There are two types: acquired and congenital. Acquired LQTS is caused by an underlying medical condition, such as drugs that prolong the QT interval, electrolyte imbalances (such as caused by anorexia), and bradycardia. Congenital LQTS is inherited from one or both parents. In addition, there are 12 different subtypes of LQTS, labeled LQT1 to LQT12.

How to calculate QTC?

So it's necessary to calculate the corrected QT interval (QTc) using the Bazett formula: QT interval divided by the square root of the R-R interval. The R-R interval is measured from one R wave to the next R wave that comes before the QT interval being measured. For example, if the QT interval measures 0.44 second and the R-R interval measures 0.86 second, then the QTc is 0.47.

When to consider LQTS?

With any patient in your care, always consider LQTS if the patient has fainted and it can't be explained by any other medical condition.

What is the best treatment for congenital LQTS?

Beta-blockers are the main medication used for the management of congenital LQTS. If medication isn't successful, then the patient may need dual chamber pacing at a rate to shorten the QT interval. For patients at increased risk or those who continue to experience severe life threatening cardiac events, an implantable cardioverter defibrillator is strongly recommended.

What is a QT syndrome?

Core tip:Long QT syndrome is a cardiac conduction disorder characterized by prolongation and increased dispersion of ventricular repolarization, manifested by lengthening of the QT interval on the surface electrocardiography. This review furnishes important key points for preoperative optimization, intraoperative anesthetic agents and postoperative care in order to fill the lack of definitive guidelines on anesthetic management of c-long QT syndrome.

What is the torsadogenic effect of LQTS?

Drugs used for premedication and sedation. Since anxiety and pain can trigger arrhythmias in patients with LQTS, pre-anesthetic medication is recommended.

What causes LQTS in anesthesia?

Ninety-five percent of drug-induced LQTS is due to the obstruction of the rapid component of the late correcting potassium current (Ik-r), which physiologically allows the rapid potassium outflow[4]. Ikrand the slow component of the same channel (Ik-s) are responsible for the repolarization of cardiomyocytes. Some anesthetics and some drugs used in premedication may lead to QT-prolongation. The available data on the prevention of lethal TdP during anesthesia in patients with c-LQTS is scant and conflicting: only case reports and small case series with different outcomes, even when using the same anesthetic agent, have been published[2,5-19]. Although a-LQTS is of significant interest, this review focuses on the anesthetic recommendations for patients diagnosed with c-LQTS. Our aim is to provide some key points which could help both the cardiologists and the anesthetists when approaching a patient with LQTS candidate for anaesthesiological procedures. Firstly, we describe which drugs should be avoided in LQTS and then we move on the specific topic of the review describing the anaesthesiological management of patients with LQTS.

What is LQT1 gene?

LQT1 is associated with a mutation in the KvLQT1gene (also known as KCNQ1), which codes for a protein that co-assembles with another protein (minK) to form the Ik-s[72] . In patients with LQT2 arrhythmic events are usually triggered by auditory stimuli or sudden startle[73]. LQT2 is caused by the loss of Ikr[72].

What is the most common phenotype of C-LQTS?

Genetic testing can help to recognize specific subtypes of c-LQTS. The most common phenotypes are LQT1, LQT2 and LQT3. People with LQT1, the most common variant of LQTS, are more likely to have a cardiac event during exercise than patients with LQT2 or LQT3.

How long should a patient stay in a postoperative unit?

Postoperative management of patients with c-LQTS should include the permanence in a postsurgical intensive care unit for at least 24 h, avoiding stimuli that could trigger TdP. An adequate postoperative analgesia and beta-blocking must be guaranteed. Postoperative nausea and vomiting (PONV) prevention can not be performed with setrones (ondansetron, granisetron and dolasetron) in patients with c-LQTS because these drugs block not only the 5HT3receptors but also the HERG channel, determining a prolongation of repolarization. A study by Charbit et al[67] demonstrated that 4 mg of ondansetron induced prolongation of the QTc, similar to the effect of 0.75 mg of droperidol, therefore questioning the greater safety of ondansetron when compared to droperidol in the treatment of PONV; Accordingly Staikou et al[32] advise against its use in patients with c-LQTS.

What drugs are used to reduce catecholamines?

Lastly, an adequate sedoanalgesia reduces catecholamine release; the most used drugs are morphine, meperidin and fentanyl. Though the effects of fentanyl on QTc interval are conflicting, fentanyl and morphine have been used in patients with c-LQTS without any adverse effect[17,33-36]. On the other hand, Song et al[37] recently reported that the intravenous injection of meperidine led to QTc prolongation, polymorphic ventricular tachycardia and ventricular fibrillation, in a 16-year-old boy without neither underlying cardiac disease nor mutation in LQTSgenes, but with a single nucleotide polymorphism, including H558R in SCNA5Aand K897T in KCNH2. Alfentanil does not extend repolarization time[2]. On the contrary, sufentanil prolongs QTc interval[38].