Short QT Syndrome

Short QT Syndrome

Overview

Short QT syndrome (SQTS) is an inherited type of abnormal heart rhythm. It belongs to a group called channelopathies, characterized by a change in the flow of ions through the cell membrane. In the heart, this movement of particles (electrically charged particles of sodium, calcium, potassium, and chloride) through ion channels generates the cardiac action potential - an electrical signal, which propagates through the cells to induce a contraction of the heart - and is therefore the cornerstone of the heart’s electrical activity. SQTS is thought to be principally caused by defective functioning of both potassium and calcium ion channels, which leads to abnormal shortening of the QT interval. (2)

The Q-T interval is the section on the ECG that represents the time it takes for the electrical signal to travel through the heart's ventricles and then recharge. It also corresponds to the time it takes for the heart to contract and recover from the action. The heart rate in SQTS is usually normal, but the total recovery time is much shorter. Another difference from a healthy heart is that the Q-T interval does not change along with heartbeat changes. Normally the interval gets longer with a slower heart rate and shorter with a rapid one. (3)

Shortening of the QT interval highly increases the risk of abnormal heart rhythms, because the myocardium discharges and recharges faster than normal. These changes to the rhythm often include atrial fibrillation, ventricular fibrillation and ventricular tachycardia. (1) 

In a normal heart rhythm, electrical signals pass through the heart muscle at regular intervals. In fibrillation, the impulses propagate rapidly in a disorderly manner without any regularity. The consequence is that the relevant cardiac compartments lose their ability to pump blood effectively. 

Atrial fibrillation (AFib) causes an irregular, very rapid heart rhythm because the chaotic impulses from the atria are also transmitted with absolute irregularity (although at a lower frequency) to the ventricles. 

Ventricular tachycardia (VT) is a rapid heart rate emanating from the lower chambers of the heart. Longer periods are particularly dangerous as it can easily progress to ventricular fibrillation and cardiac arrest.

Ventricular fibrillation (VF) causes the ventricles to merely quiver instead of contracting, the heart is unable to pump blood at all, and cardiac arrest occurs. 

Prevalence & Risk factors

Due to the limited number of documented cases worldwide (to date, literature reports approximately 300 cases after two decades of research), it is difficult to determine the true prevalence on a global scale. The relevance of studies on SQTS is also questionable due to the lack of diagnostic criteria such as QT cut-off value or knowledge of risk factors. Based on cohort studies in recent years, the prevalence is estimated to be between 0.02 and 0.1% in adults, while in the paediatric population the prevalence should be 0.05%. (4, 5)   

To date, risk stratification and the lack of risk identifiers represent the biggest challenge for the management of patients with SQTS, mainly due to the low number of documented patients. Scoring systems consist primarily of four independent components: ECG, clinical history, family history, and genotype. (1, 4, 6).

Genetics

SQTS is a genetically heterogeneous disease (both in its genotype and phenotype). Recent studies describe mutations in eight different genes (three causing gain of function and five loss of function) that encode different cardiac ion channels, but also the carnitine transporter and the chloride-bicarbonate anion exchanger. These forms were identified by the researchers and marked SQT1 to SQT8 based on the chronology of their discovery. (1) Many of the genes involved in SQTS are also involved in LQTS (long QT syndrome), but with the opposite mutation. (1) Most cases of SQTS run in families and follow an autosomal dominant pattern, however this condition can also be acquired and it is important to differentiate between the two. (4) 

Signs & Symptoms

The clinical presentation of SQTS is variable, and up to 40% of cases are asymptomatic. (4) The most common clinical manifestations are:

  • dizziness
  • palpitations
  • atrial fibrillation
  • ventricular arrhythmias
  • syncope
  • sudden cardiac death (SCD) - it can be a reason behind sudden infant death syndrome (SIDS)

If the condition causes atrial fibrillation, other symptoms such as shortness of breath, fatigue, chest pain or even thromboembolic events might be present as well. (1, 4) 

Diagnosis

The main problem in clinical diagnosis is the cut-off value of the QT and QTc (the value of the interval corrected for the patient's heart rate) and its definition. Although an ECG finding may be the first step towards a correct diagnosis, the presence of a short QT interval alone is not sufficient for a diagnosis. Clinical history, family history and the results of genotype testing often contribute to the final diagnosis. (1)

At present, guidelines suggest the following diagnostic criteria: (4)

  1. ECG finding of QTc ≤ 340 ms

or

  1. ECG finding of QTc ≤ 360 ms and one or more of the following: (1, 4)
  • confirmed pathogenic mutation
  • family history of SQTS
  • family history of sudden cardiac death before the age of 40
  • survival from a VT/VF episode in the absence of other heart disease

Patients can also be screened for SQTS in presence of: (3)

  • Survival of sudden cardiac death (SCD)
  • Clinical history of ventricular tachycardia and/or fibrillation without a known cause
  • Anamnesis of unexplained syncope
  • Atrial fibrillation at a young age
  • Family history of SQTS and/or SCD

As mentioned, this condition can also be acquired and as such can often be reversed with the right treatment. Therefore, it is always important to distinguish between the two. Acquired causes of short QT interval include: (1)

  • hyperkalemia
  • hypercalcemia
  • acidosis
  • hyperthermia
  • effect of drugs like digitalis
  • effect of acetylcholine or catecholamine
  • myocardial ischemia
  • increased vagal tone

Therapy

There are basically two options of treatment:.

  1. Implantable cardioverter-defibrillator (ICD)

An ICD is a device that continuously monitors the heart rhythm and sends an electrical impulse to the heart muscle when an arrhythmia is detected. This causes the heart rhythm to reset to normal. (3) ICDs are recommended for symptomatic patients who have either survived sudden cardiac arrest and/or have documented spontaneous sustained ventricular tachycardia with or without a history of syncope. (1, 6)

  1. Medications

Pharmacological treatment is used primarily to reduce the likelihood of needing ICD discharges. It may also be the primary treatment modality in patients who refuse ICDs, in patients with an absolute contraindication to ICD placement, or in very young patients in whom ICD implantation is problematic. (1)  Data regarding pharmacologic therapy in SQTS are however very limited.

Prevention

The only established predictor of cardiac arrest in a patient with SQTS is a history of cardiac arrest. Therefore, the optimal primary prevention strategy remains a matter of controversy. Currently, guidelines recommend ICDs as the first and most effective therapeutic measure in patients who have experienced VT/VF or survived cardiac arrest. (1)

To prevent the SCD altogether, profound screening is probably the most helpful tool at the moment. This is useful especially in people at higher risk of SQTS: (7)

  • Family members of sudden death victims
  • Patients with documented or suspected ventricular arrhythmias

Prognosis

Early correct diagnosis and optimal treatment significantly improve the prognosis of patients with SQTS, although the exact long-term prognosis of these patients is still difficult to assess due to the small number of documented cases. (1)  

Recommendations

  • If you experience palpitations, shortness of breath, unexplained fainting, dizziness of fatigue, do not underestimate the condition and consult it with your doctor
  • If your family member has been diagnosed with SQTS, you should also be evaluated for the condition. The evaluation should always include a screening, ECG and genetic testing

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Recommendations

  • If you experience palpitations, shortness of breath, unexplained fainting, dizziness of fatigue, do not underestimate the condition and consult it with your doctor
  • If your family member has been diagnosed with SQTS, you should also be evaluated for the condition. The evaluation should always include a screening, ECG and genetic testing

Sources

  1. Short QT syndrome - UpToDate. (n.d.). Retrieved April 18, 2022, from https://www-uptodate-com.ezproxy.is.cuni.cz/contents/short-qt-syndrome?search=Short%20QT%20syndrome&source=search_result&selectedTitle=1~41&usage_type=default&display_rank=1
  2. Dewi, Ivana P, and Budi B Dharmadjati. “Short QT syndrome: The current evidences of diagnosis and management.” Journal of arrhythmia vol. 36,6 962-966. 6 Oct. 2020, doi:10.1002/joa3.12439
  3. Short Q-T Syndrome (SQTS). (n.d.). Retrieved April 19, 2022, from https://my.clevelandclinic.org/health/diseases/17469-short-q-t-syndrome-sqts
  4. Campuzano, O., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Brugada, J., & Brugada, R. (2018). Recent Advances in Short QT Syndrome. Frontiers in cardiovascular medicine, 5, 149. https://doi.org/10.3389/fcvm.2018.00149
  5. Nikoo, M. H., Heiran, A., Mashayekh, F., Rezaianzadeh, A., Shiravani, A., & Azadian, F. (2022). A descriptive report on short QT interval in Kherameh branch of the PERSIAN cohort study. Scientific reports, 12(1), 2898. https://doi.org/10.1038/s41598-022-06835-y
  6. Rudic, B., Schimpf, R., & Borggrefe, M. (2014). Short QT Syndrome – Review of Diagnosis and Treatment. Arrhythmia & Electrophysiology Review, 3(2), 76. https://doi.org/10.15420/AER.2014.3.2.76
  7. Priori, S. G., Blomstrom-Lundqvist, C., Mazzanti, A., Bloma, N., Borggrefe, M., Camm, J., Elliott, P. M., Fitzsimons, D., Hatala, R., Hindricks, G., Kirchhof, P., Kjeldsen, K., Kuck, K. H., Hernandez-Madrid, A., Nikolaou, N., Norekval, T. M., Spaulding, C., van Veldhuisen, D. J., Kolh, P., … Parkhomenko, A. (2015). 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac deathThe Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal, 36(41), 2793–2867. https://doi.org/10.1093/EURHEARTJ/EHV316
  8. QT Interval • LITFL • ECG Library Basics. (n.d.). Retrieved April 26, 2022, from https://litfl.com/qt-interval-ecg-library/
  9. Short QT syndrome - UpToDate. (n.d.). Retrieved April 18, 2022, from https://www-uptodate-com.ezproxy.is.cuni.cz/contents/short-qt-syndrome?search=Short%20QT%20syndrome&source=search_result&selectedTitle=1~41&usage_type=default&display_rank=1
  10. Short QT Syndrome. (n.d.). Retrieved April 18, 2022, from https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-9/Short-QT-Syndrome
  11. Antzelevitch, C., & Burashnikov, A. (2011). Overview of Basic Mechanisms of Cardiac Arrhythmia. Cardiac electrophysiology clinics, 3(1), 23–45. https://doi.org/10.1016/j.ccep.2010.10.012
  12. Priori, S. G., Blomstrom-Lundqvist, C., Mazzanti, A., Bloma, N., Borggrefe, M., Camm, J., Elliott, P. M., Fitzsimons, D., Hatala, R., Hindricks, G., Kirchhof, P., Kjeldsen, K., Kuck, K. H., Hernandez-Madrid, A., Nikolaou, N., Norekval, T. M., Spaulding, C., van Veldhuisen, D. J., Kolh, P., … Parkhomenko, A. (2015). 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac deathThe Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal, 36(41), 2793–2867. https://doi.org/10.1093/EURHEARTJ/EHV316

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