Kembara Xtra - Medicine - Prolonged QT Interval

Kembara Xtra - Medicine - Prolonged QT Interval 
The time between the start of the QRS complex and the end of the T wave on a surface electrocardiogram (ECG) is known as the QT interval. This is the time frame between the beginning of ventricular depolarization and the conclusion of the ventricular myocardium's repolarization, or ventricular systole. If the QT interval is 50% or less of the RR interval, it is considered normal.
 QTc, or corrected QT interval: Heart rate and the QT interval are inversely related. The QTc, which measures the QT interval at a heart rate of 60 beats per minute, is the QT interval corrected for heart rate. View formulae.
The standard definition of prolonged QTc is >450 ms for adult males and >470 ms for adult females (1):
- In men, 430 to 450 ms is regarded as borderline.
- In women, 450 to 470 ms are regarded as borderline.- In youngsters aged 1 to 15, 440 to 460 ms are regarded as borderline.
The majority of extended QT instances are acquired, however hereditary long QT syndrome (LQTS) is caused by a number of genetic abnormalities.
 Prolonged QTc from any source can trigger the polymorphic VT known as torsade de pointes (TdP), which can produce syncope, lightheadedness, and abrupt cardiac death from ventricular fibrillation (VF).

Prevention Incidence
The likelihood of drug-induced QTc prolongation and TdP varies depending on the medicine and a number of other variables. Although it's hard to predict exact incidents, they could range from 500,000 to 600,000.


Prevalence
According to estimates, 1/2,500 to 1/7,000 babies result in hereditary LQTS.
A cardiac arrhythmia linked to LQTS may cause 5,000 fatalities each year in the US.

Pathophysiology and Etiology 
Demographics acquired: aging population, female sex
- Hyperkalemia, hypocalcemia, and hypomagnesemia are disorders of the electrolytes.
- Noncardiac illness: hypothyroidism, renal dysfunction, and hepatic dysfunction
- Cardiac disease: myocardial ischemia, LVH, and heart failure (2)
- Hypotheses: fast conversion from atrial fibrillation/bradycardia, QT interval rise >60 ms 
- drug (*indicates "high-risk" TdP drug
Quinidine, procainamide, dronedarone, dofetilide, sotalol, disopyramide, and amiodarone are antiarrhythmic drugs. Haloperidol, chlorpromazine, thioridazine, and pimozide are antipsychotic drugs, especially if administered intravenously.
 Antidepressants: the most frequently prescribed medications at fault (SSRIs, SNRIs, trazodone, TCAs)
Antiemetics include metoclopramide, ondansetron, and promethazine. Opioids include methadone* and buprenorphine. Antihistamines include cetirizine, hydroxyzine, and diphenhydramine. Decongestants include pseudoephedrine and phenylephrine. Stimulants include albuterol and phentermine. Miscellaneous includes chloroquine*, pentamidine*,
– Drug-induced QT prolongation is frequently caused by blockade of the IKr channel, which delays phase 3 rapid repolarization. Repolarization occurs through the efflux of potassium from the cell (phases 2 and 3) by rapid (IKr) and slow (IKs) components of the delayed rectifier, which is represented by the T wave on an ECG. Both times, abnormal ion channel function results in transmural dispersion of repolarization currents across the myocardium, triggering shortly after depolarizations and potentially developing into TdP. A prolonged QT interval alone does not indicate an impending risk for TdP; although TdP is frequently self-limited, it can nevertheless result in syncope or VF degradation.

Genetics There are 13+ different genotypes associated with LQTS, and penetrance is highly variable, making diagnosis and treatment difficult.
The most common cause of LQTS is LQT1 (40–55%). Arrhythmias brought on by sympathetic activity (stress/exercise—especially swimming) and shorter ventricular repolarization due to the loss of function of the KCNQ1 gene, which codes for the IKs transport protein.
LQT2 (30–45%) is the result of a KCNH2 gene mutation that leads in a deficiency in the IKr transport protein; it puts a person at risk for cardiac events because it causes sudden catecholamine surges from auditory stimuli or emotional arousal (postpartum)
A mutation in the SCN5A gene that results in the alpha subunit of the INa transport protein gaining function is the primary cause of LQT3 (5–10%). During sleep, when the inward flow of sodium is enhanced at low heart rates, the cell accumulates too much sodium, lengthening the time it takes to repolarize.
1% of the total frequency is between LQT4 and LQT13.
As a result of homozygous or compound heterozygous mutations in the KCNQ1 or KCNE1 genes, Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive condition.
reduced IKs transport protein activity; linked to sensorineural hearing loss
The most typical is Romano-Ward syndrome (RWS). the 13 discovered gene variants; autosomal dominant, variable penetrance, and normal hearing
Others include Timothy syndrome (LQT8) and Andersen-Tawil syndrome (LQT7). Both are relatively uncommon.


Risk Elements 
Risk factors for the dreaded complication TdP include the following:
 Females (two times higher risk)
 QTc > 500 ms (risk increased by 2 to 3 times)
 QTc greater than baseline by 60 ms
 The chance of getting TdP increases by 5-7% for every 10 ms increase in the QTc.
 TdP history History of syncope or presyncope
The Bradycardia
 Liver or renal disease (by raising blood levels of drugs that prolong QT)
 Drugs that extend QTc - High doses - Rapid infusions - Combinations of drugs Drugs that block CYP3A4 Electrolyte disorders - Hypokalemia - Hypomagnesemia - Hypocalcemia
Exercise, mental stress, loud noises, and postpartum catecholamine surges are all risk factors for inherited LQTS.

Prevention 

 Causing drugs, including combinations with possibly cumulative effects, should be avoided (or used with discretion).
 Have enough electrolytes (target Mg >2, K 4.5 to 5.0).
 Address underlying illnesses.
 When you have LQTS, stay away from demanding sports and other stimulating activities like roller coasters and chilly water jumps.
Avoid abrupt loud noises in LQTS (phones, doorbells, alarm clocks).
Although there is growing evidence that LQTS athletes can participate safely in class 1A activities (such as bowling, golf, and riflery), the 36th Bethesda Conference advises against it.


Accompanying Conditions 
Anorexia nervosa and bulimia are two examples of illnesses that can cause electrolyte imbalances due to excessive vomiting and/or diarrhea.
Timing syndrome (LTQTS type 8): protracted QT interval, hand/foot, face, and neurodevelopment; Andersen-Tawil syndrome (LTQS type 7): muscle weakness, facial dysmorphism; JLNS: linked with significant sensorineural hearing loss

Examine for syncope, presyncopal episodes, palpitations, and associated triggering events (emotional triggers, swimming, or diving) based on history and incidental ECG findings in asymptomatic patients.
A thorough medication history, a history of syncope or sudden cardiac death in the family, a history of seizures in the patient or family members (tonic-clonic movement may be caused by cerebral hypoperfusion during bouts of ventricular arrhythmia or syncope), and congenital deafness.

clinical assessment 

The physical examination is usually normal, but there may be indications of underlying heart disease, hypothyroidism, hepatic dysfunction, or renal impairment, as well as congenital deafness, which is common in many types of LQTS.


Long QT interval differential diagnosis may include consider QT-prolonging medications, hypokalemia, hypomagnesemia, hypercalcemia, neurologic disorders causing subarachnoid bleeds, and structural heart disease.
The following conditions should also be considered in the differential diagnosis of other causes of syncope or sudden death: Sudden infant death syndrome (SIDS), vasovagal (neurally mediated) syncope, orthostatic hypotension, seizures, familial VF, cardiomyopathies (HCM, DCM, ARVC), Brugada syndrome, anomalous coronary artery, and catecholaminergic polymorphic VT.


Laboratory Results 
Initial examinations (lab, imaging)
ECG Metabolic panel, in particular potassium, magnesium, and calcium. TSH Follow-Up Examinations & Particular Considerations
To test for cardiomyopathy, perform an echocardiogram.
Consider provocative testing (epinephrine infusion, exercise stress testing) to assess for QTc interval alterations and/or coronary artery disease. Outpatient cardiac rhythm monitoring (Holter, Event, or Implantable monitoring).
Testing for LQTS mutations genetically
Interpretation of Tests
The optimal time to measure the QT interval is between the beginning of the QRS and the end of the T wave; this is done most frequently in lead II or V2.
There are numerous approaches to calculate QTc utilizing the RR interval that comes right before the QT interval. The most popular methods (1), (2) for applying the Bazett formula.
Formula for Framingham: QT + 0.154 (1 RR)
QTc = QT / (RR) (all measures in seconds, and RR determined by direct measurement or 60/heart rate) is the Bazett formula.
- The Fridericia formula, like the Bazett formula, uses the cube root RR interval and is written as QTc = QT / (RR)1/3.

Management 
According to ACLS recommendations, treat VT, TdP, and VF urgently.
Remove the problematic substances and adjust the electrolytes.
In the case of gastrointestinal disease, an eating disorder, or neurologic diseases causing subarachnoid bleed, treat the underlying ailment.
Avoid triggers if they are known.
Drug-induced TdP may be treated with transvenous cardiac pacing or isoproterenol to prevent bradycardia. Maintain a heartbeat of 90 to 110 beats per minute.


First Line of Medicine

For TdP, administer 2 g of magnesium sulfate over a period of 2 to 5 minutes, followed, if necessary, by a continuous infusion of 2 to 4 mg/min. Bolus injections commonly cause flushing as a side effect. Patients with renal insufficiency should be watched out for magnesium toxicity.
 Although thorough studies are lacking, propranolol or nadolol are widely recognized as the best -blockers for managing hereditary LQTS and preventing life-threatening arrhythmias.
The risk of deadly arrhythmias can be reduced but not entirely by beta-blockers.
Implantable cardiac defibrillators (ICDs) with or without pacemakers may be recommended for high-risk individuals who are still experiencing symptoms after taking a -blocker (2)[B].
Next Line
Metoprolol or atenolol may be utilized, although switching -blockers may cause fatal or very close to fatal occurrences.

Referral 

Referrals should be made in patients with symptomatic prolonged QT as well as those with congenital or hereditary LQTS, as well as those who have a family history of sudden cardiac death. If congenital LQTS is suspected in a patient with a history of sudden cardiac death, the patient should be referred to cardiology for further testing and diagnosis.

Further Therapies 

For LQTS type 3, trials of drugs that inhibit cardiac sodium channels are currently being investigated.

Surgical Techniques 

ICDs are not effective at preventing TdP, so patients should continue receiving the best medical care in addition to an ICD if they have a history of serious cardiac events (regardless of whether they were treated with the right medical therapy or not).
Prior to the development of -blockers, left cervical-thoracic sympathetic denervation was utilized to treat symptomatic LQTS. It is still a choice for LQTS patients who have not responded to -blocker medication.


Healthcare Alternatives 

In general, many nutritional supplements and herbal therapies can be hazardous to people with LQTS. However, little study has been done on this type of treatment for those with LQTS.
Such over-the-counter medications should be avoided in this demographic as several of them have been associated to cardiac arrhythmias.


Admission 
As recommended by ACLS, rapidly treat TdP, VT, and VF.
Correct electrolytes as soon as possible. Check for inherited QT prolongation. If no reason is discovered, think about hereditary LQTS.
Patients who have a prolonged QTc and syncope or near syncope should be telemetry monitored.
 If starting or combining drugs with QT-prolonging pharmaceuticals, obtain a baseline ECG. Then, after the drug achieves steady state, at 30 days, and annually after that.
Avoid using QT-extension drugs when treating patients with hereditary LQTS.
Patients at risk for LQTS should be informed about arrhythmia symptoms.
 Keep an eye on electrolytes, treat hypomagnesemia and hypokalemia as away, and stop or alter the problematic drugs.
Avoid emotional tension or abrupt loud noises if you have LQTS.
Consider using clinical decision support tools to evaluate the risk of drug-induced risk of QT prolongation while taking into account the clinical context. Review the adherence to -blocker therapy.


Patient Follow-Up Monitoring
Ask patients with QTc prolongation about syncope, presyncope, and palpitations during routine visits.
Consider an ECG and/or outpatient heart rhythm monitoring while adding or adjusting a medication's dosage.
Any cause of symptomatic QTc prolongation warrants prompt assessment. Check for electrolyte imbalances and make any necessary corrections, which may include outpatient heart rhythm monitoring and/or ECG.

Diet
Those who have LQTS are frequently helped by consuming more potassium, either naturally or through supplements.
Alcohol, illicit/recreational drugs, caffeine-containing products, and supplements with stimulant properties (such as ginseng) should all be avoided as they all raise the risk of life-threatening arrhythmias. QT prolongation has been noted in the context of the ketogenic diet and diabetic ketoacidosis regardless of electrolyte disturbances.

Patient Education — Inform patients with QTc prolongation about the adverse effects and drug interactions of their prescription drugs.
Depending on their particular gene mutation, patients with congenital types of LQTS should be aware of and steer clear of triggers.
 Take into account the psychological and emotional effects.
Fortescue explains the personal consequences of LQTS in additional reading.

Prognosis 
After the offending substances are removed and the metabolic anomalies return to normal, acquired LQTS will disappear.
Patients who have underlying cardiovascular disease may have a higher mortality risk and need further treatment.
Untreated congenital LQTS has a very dismal prognosis.
Perhaps 20% of untreated syncope sufferers pass away within a year, and 50% do so within ten years.

VFib, abrupt cardiac death, seizures, loss of consciousness, drowning, and other incidents caused by TdP complications

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