The heart has an electrical system that allows it to contract in a rhythm. A key aspect of this electrical system is depolarization and repolarization. The electrical activity is conducted through the sinoatrial (SA) node and atrioventricular (AV) node and into the ventricles. This electrical activity is clearly outlined on an electrocardiogram (ECG) with P waves, the QRS complex, and T waves. The P wave represents the electrical activity of the atrium. The QRS complex shows the depolarization of the ventricles. Lastly, the T wave shows the repolarization of the ventricles.
The focus of this article is on the QT interval. It is measured from the Q wave until the T wave, and the QT interval clinically represents the repolarization of the ventricles. When measured on an ECG, the QT interval lengthens when the heart is beating slower and shortens when the heart is beating faster. That is why an adjusted version of the QT interval is used: QTc. This allows for an accurate QT interval at lower and higher heart rates. There are different formulas used to obtain the QTc interval.
Bazett is the most commonly used formula and is done by dividing the QT interval by the square root of the R-R interval. Fridericia is a similar formula, except it uses the cube root of the R-R interval. Framingham is a more complex formula, but the literature has shown it may be the most superior formula. Bazett's is automatically calculated on most ECG machines, and its limitations are underestimation and overestimation of the QTc in the cases of bradycardia and tachycardia, respectively. Its accuracy is largely limited to heart rates of 60 to 100 beats per minute, and clinicians must factor in the heart rate when assessing the QTc.
A normal QTc in a male is 440 ms or less, and in a female, it is 460 ms or less. Those with prolonged QT are at risk for one of the potentially deadly arrhythmias known as torsades de pointes. It is the most common form of polymorphic ventricular tachycardia, an unstable cardiac rhythm. This rhythm may cease on its own and go into sinus rhythm, or it may degenerate into ventricular fibrillation. The most common symptom is syncope. Patients with torsade are administered a 2-4g bolus of magnesium sulfate and must undergo cardioversion if hemodynamically unstable. Isoproterenol can also be used to increase the heart rate, thereby decreasing the absolute QT interval. It is generally accepted that QT prolongation past 500 ms carries an increased risk of torsades de pointes; however, if the QT prolongation is severely prolonged, ventricular fibrillation is a certainty.
Prolonged QT Etiologies
Literature has shown that people who have diabetes and those suffering from certain inflammatory diseases may suffer from mildly prolonged QT. This is also true in those with heart disease. No major evidence in the general population indicates changes in mortality are associated with QT prolongation. However, subsets of cardiac patients may have an increased risk of mortality if they suffer from QT prolongation.
Pharmacological agents are the most common cause of QT prolongation given the broad range of medications that may induce it. As well, torsade, which is drug-induced, is reversible by the discontinuation of the offending drug.
Antipsychotics: Haloperidol, ziprasidone, quetiapine, thioridazine, olanzapine, risperidone
Antiarrhythmics: Amiodarone, sotalol, dofetilide, procainamide, quinidine, flecainide
Antibiotics: Macrolides, fluoroquinolones
Antidepressants: Amitriptyline, imipramine, citalopram, amitriptyline
Others: Methadone, sumatriptan, ondansetron, cisapride
A vast number of medications prolong the QT interval. They are preferably classified based on the degree of QT prolongation they induce. This is specifically medication dependent. Caution is advised when combining QT-prolonging medications or when using these medications in those with electrolyte abnormalities.
Many commonly used medications, such as diphenhydramine and azithromycin, exhibit QT-prolonging effects. However, the degree of QT prolongation is not severe enough to warrant caution in healthy patients. These medications bind to the human ether-related gene (hERG) channels and reduce electrical conduction through the potassium ion channels. This results in delayed repolarization of the heart.
The QT interval is measured from the beginning of the QRS complex to the end of the T wave. Mechanisms that prolong the action potential duration can prolong the QT interval. Specifically, this occurs via delaying the third phase of repolarization. When the hERG channels are altered, there are changes made to the potassium ion channels. This causes an impairment of the channel's ability to conduct electrical activity. The result is prolonged cardiac repolarization.
This mechanism can occur via genetic changes to hERG and/or drug-binding to these channels. Different drugs will induce changes in the hERG channels to variable degrees. Hence, different medications induce different levels of QT prolongation.
QT prolongation increases the risk of torsades de pointes, a potentially lethal arrhythmia. Torsades de pointes is the most common form of polymorphic ventricular tachycardia; it is initiated when a premature ventricular contraction occurs in the setting of a prolonged QT interval. This is known as the "R on T" phenomenon. It may cease on its own and return to sinus rhythm, or it may degenerate into ventricular fibrillation.
The clinical feature of this arrhythmia is often syncope. However, it can be asymptomatic. If it degenerates into ventricular fibrillation, death is the likely outcome if there is no intervention.
Patients diagnosed with long QT syndrome or any genetic causation of prolonged QT syndrome should use these medications with caution. Patients with hypokalemia, hypomagnesemia, and hypocalcemia should be put on QT-prolonging medications with caution. Certain electrolyte derangements prolong QT, which would be further exacerbated by these medications.
Medication interactions are another form of dangerous contraindication. Certain QT-prolonging medications are substrates of the cytochrome P450 (CYP450) system. If a patient is using a CYP450 inhibitor medication at the same time, there is a risk of significantly greater QT prolongation.
Patients using medications that prolong the QT interval should ideally be monitored with an ECG. Some medications induce minimal QT prolongation, and if there is no preexisting QT prolongation, then monitoring is unnecessary. A normal QTc in men is 440 ms or less, and in women, it is 460 ms or less. It is ideal to have patients within those parameters when on a QT-prolonging medication. A longer QTc is tolerated until it approaches and/or exceeds 500 ms.
The monitoring of electrolytes, specifically potassium, magnesium, and calcium, should be done in patients who have QT prolongation. The risk of further QT prolongation and torsades de pointes is increased when electrolyte abnormalities coexist with these medications.
Treatment of QT prolongation requires an interprofessional approach. Genetic causes require a specific diagnosis, which allows for the avoidance of aggravating factors. The usage of beta-blockers may lower the risk of torsades de pointes.
Pharmacological etiologies of QT prolongation are treated with ceasing the offending medication. Any coexisting electrolyte abnormalities should be treated. Optimization of potassium, magnesium, and calcium is especially important to minimize the risk of torsades de pointes.
At the time of admission and discharge, the nurse should make a note of all medications that affect the QT interval and notify the team. Cardiology nurses are responsible for monitor patients, administering treatments and notifying physicians, nurse practitioners, or physician assistants of changes in status. Similarly, the pharmacist must keep track of all the medications the patient is prescribed and speak to the provider if any medications can alter the QT interval. In most cases, medication-induced prolonged QT interval can be prevented by a proactive approach. [Level 5]
|||Draghici AE,Taylor JA, The physiological basis and measurement of heart rate variability in humans. Journal of physiological anthropology. 2016 Sep 28 [PubMed PMID: 27680542]|
|||Gianni C,Burkhardt JD,Trivedi C,Mohanty S,Natale A, The role of the Purkinje network in premature ventricular complex-triggered ventricular fibrillation. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2018 Aug [PubMed PMID: 30066290]|
|||Postema PG,Wilde AA, The measurement of the QT interval. Current cardiology reviews. 2014 Aug [PubMed PMID: 24827793]|
|||Al-Akchar M,Siddique MS, Rhythm, QT Prolongation null. 2018 Jan [PubMed PMID: 28722890]|
|||Indik JH,Pearson EC,Fried K,Woosley RL, Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart rhythm. 2006 Sep [PubMed PMID: 16945790]|
|||Luo S,Michler K,Johnston P,Macfarlane PW, A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs. Journal of electrocardiology. 2004 [PubMed PMID: 15534815]|
|||Hazeki D,Yoshinaga M,Takahashi H,Tanaka Y,Haraguchi Y,Abe M,Koga M,Fukushige T,Nagashima M, Cut-offs for screening prolonged QT intervals from Fridericia's formula in children and adolescents. Circulation journal : official journal of the Japanese Circulation Society. 2010 Aug [PubMed PMID: 20534944]|
|||Vandenberk B,Vandael E,Robyns T,Vandenberghe J,Garweg C,Foulon V,Ector J,Willems R, Which QT Correction Formulae to Use for QT Monitoring? Journal of the American Heart Association. 2016 Jun 17 [PubMed PMID: 27317349]|
|||Ching CK,Tan EC, Congenital long QT syndromes: clinical features, molecular genetics and genetic testing. Expert review of molecular diagnostics. 2006 May [PubMed PMID: 16706739]|
|||Lazzerini PE,Capecchi PL,Laghi-Pasini F, Assessing QT interval in patients with autoimmune chronic inflammatory diseases: perils and pitfalls. Lupus science [PubMed PMID: 28074146]|
|||Recanatini M,Poluzzi E,Masetti M,Cavalli A,De Ponti F, QT prolongation through hERG K( ) channel blockade: current knowledge and strategies for the early prediction during drug development. Medicinal research reviews. 2005 Mar [PubMed PMID: 15389727]|
|||Pollard CE,Abi Gerges N,Bridgland-Taylor MH,Easter A,Hammond TG,Valentin JP, An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk. British journal of pharmacology. 2010 Jan [PubMed PMID: 20141516]|
|||Saxena P,Hortigon-Vinagre MP,Beyl S,Baburin I,Andranovits S,Iqbal SM,Costa A,IJzerman AP,Kügler P,Timin E,Smith GL,Hering S, Correlation between human ether-a-go-go-related gene channel inhibition and action potential prolongation. British journal of pharmacology. 2017 Sep [PubMed PMID: 28681507]|
|||Oksuz F,Sensoy B,Sahan E,Sen F,Baser K,Cetin H,Unal S,Ozeke O,Topaloglu S,Aras D, The classical [PubMed PMID: 26304578]|
|||Mourad A,Stiber JA,Perfect JR,Johnson MD, Real-world implications of QT prolongation in patients receiving voriconazole and amiodarone. The Journal of antimicrobial chemotherapy. 2018 Oct 8 [PubMed PMID: 30295798]|
|||Mahmud R,Gray A,Nabeebaccus A,Whyte MB, Incidence and outcomes of long QTc in acute medical admissions. International journal of clinical practice. 2018 Nov [PubMed PMID: 30222237]|
|||Cheung D,Cumbler E,Hale G,Pell J, Reining in the QTc: reducing the risk of Torsades de Pointes across a major health system. Journal of the American Medical Informatics Association : JAMIA. 2018 Sep 1 [PubMed PMID: 29961858]|
|||Golzari H,Dawson NV,Speroff T,Thomas C, Prolonged QTc intervals on admission electrocardiograms: prevalence and correspondence with admission electrolyte abnormalities. Connecticut medicine. 2007 Aug [PubMed PMID: 17879860]|
|||Ravens U, Sex differences in cardiac electrophysiology. Canadian journal of physiology and pharmacology. 2018 Oct [PubMed PMID: 30001496]|
|||Thomas SH,Behr ER, Pharmacological treatment of acquired QT prolongation and torsades de pointes. British journal of clinical pharmacology. 2016 Mar [PubMed PMID: 26183037]|