By Dr. Payal Kohli, MD, FACC
I was utterly horrified. I stood by the young man's bedside, paralyzed to do anything but stare at the rhythmic Torsades de pointes on the monitor ahead of me. It is a scene I replay in my mind often.
It started with a young man who presented with hypokalemia from toxin-mediated diarrhea. The severe hypokalemia had triggered polymorphic VT arrest due to prolonged QTc interval. Once his potassium was repleted, his underlying QTc revealed that he probably had underlying long QT syndrome, which had until then remained undiagnosed. The story doesn't end there, however. Due to his "VT arrest", he was subsequently loaded with intravenous amiodarone in the emergency room. The result was the longest QTc I have ever seen in my cardiology career.
I have always had profound respect for the QTc interval. It is a truly understated interval that we sometimes neglect while interpreting ECG. And yet, this "vulnerable period" of cardiac repolarization is perhaps one of the most important parts of the cardiac electrical cycle. A PVC during this period, or prolonging of this period, can take an otherwise structurally normal heart and stop it in an instant. I always knew the prognostic power of the QTc, but that day, I think I truly appreciated how important this interval is and how it can literally mean the difference between life and death.
QTc as a Prognostic Marker in Hospitalized Patients
One study reports that a prolonged QTc interval (500 msec) in hospitalized patients is a powerful predictor of short-term mortality after adjustment for comorbidity and reason for hospital admission.1 In the same study, QTc also predicted long-term mortality, but this effect was driven mainly by its predictive value for short-term mortality. The QTc is a powerful prognostic tool to use when discharging hospitalized patients, and I have increasingly relied on it during hospital discharge and in my post-hospitalization follow-up visits.
The important role of the QTc interval and the need to incorporate it into clinical workflows has been highlighted by its implementation at the Mayo Clinic.2 The clinic developed an automated computer-based QT alert system to screen all ECGs performed there, alerting physicians if the QTc was >=500 msec. This system also created a "pro QTc score" that incorporated clinical diagnoses, laboratory abnormalities, and medications known to affect the QT interval. This automated tool provided important prognostic information about mortality based on QTc: Those with QTc >= 500 msec had a mortality of 19% vs. 5% in those with QTc <500 msec. Additionally, the pro-QTc score was also a predictor of mortality. Interestingly, 37% of the pro-QTc score was attributed to QTc-prolonging medications.
Harnessing ECG interpretation and highlighting the QTc provides clinicians with an easy way to identify patients with high risk of mortality and to consider reducing modifiable risk factors, such as the use of QTc-prolonging medications. I often think about what might have happened differently if there was such an automated tool to warn the providers who gave my young patient amiodarone.
QTc in the Clinic for Risk Stratification
Use of QTc for prognostication can (and should) also be routinely applied to assess risk in the primary care setting. One study of 173,529 primary care patients followed over 10 years (with a median follow-up after six years) found an increased risk of cardiovascular death for both very short and very long QTc.3
The prolongation of the QTc interval resulted in worse prognosis for men, elderly patients, and patients with pre-existing cardiovascular disease. Conversely, the effect of the QTc on cardiovascular risk was insignificant for middle-aged women without cardiovascular disease. Prediction accuracy was most improved in women aged 70-90 years, with nearly 10% of them being reclassified into another risk category when QTc was added to conventional risk models.
QTc and Perioperative Risk
I see multiple patients every week who present to me for preoperative cardiac risk assessment. Most of the time, I just calculate the Revised Cardiac Risk Index (RCRI), and that's where my prognostication stops. The QTc interval, however, offers a simple, valuable, and readily available tool for clinicians to utilize in determining peri-operative risk.
One study found that the risk-adjusted HR for association between preoperative QTc and overall death was 1.47 per 1-SD increase in QTc, and 2.38 for prolonged vs. normal QT after coronary artery bypass surgery.4 It was not surprising that there was also a risk relationship between prolonged QTc interval and risk of sudden cardiac death. Based on this data, I have certainly started to analyze the QTc as part of my preoperative cardiac risk assessment.
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QTc and HIV
As reliable treatments are making HIV a chronic illness rather than a death sentence, the coexistence of HIV and cardiovascular disease has started to become more prevalent. I see many patients with HIV and heart disease in my clinic every month. Due to their higher risk of incident cardiovascular disease, as well as increased risk of HIV vasculopathy, I pay special attention to lipid management in these patients. Yet sudden cardiac death remains the third leading cause of death in HIV patients.5 This should inspire closer monitoring for other risk factors associated with sudden cardiac death, such as prolonged QTc.
Data shows that HIV-positive patients have significantly longer QTc intervals compared to the general population, with a higher incidence of pathologic QTc intervals.6 Because of this, all clinicians must analyze and be mindful of the QTc in prescribing medications to HIV-positive patients.
Measurement of the QTc
Measuring the QTc is not always straightforward or easy, especially when the rhythm is irregular (such as in atrial fibrillation) or when a U wave is present. However, the importance of accurate measurement cannot be overstated. The QTc not only provides prognostic information but also guides therapeutic decisions about which medications to prescribe or avoid in high-risk patients.
The QTc interval is an important tool in every clinician's toolbox, whether they're working in an inpatient or outpatient context, assessing niche populations or general cardiovascular risk. Correctly measuring the interval, interpreting its correct context based on age and gender, and applying its interpretation to clinical care are skills we all need to implement.
- Gibbs C, Thalamus J, Hysing J et al. QT prolongation predicts short-term mortality independent of comorbidity. EP Europace. Aug. 2019; 21 (8): 1254-1260. https://academic.oup.com/europace/article/21/8/1254/5432721?login=false
- Haugaa KH MD PhD, Bos JM MD PhD, Tarrell RF MD PhD, et al. Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clinic Proceedings. Apr. 2013; 88 (4): 315-325. https://www.mayoclinicproceedings.org/article/S0025-6196(13)00071-2/fulltext
- Nielsen JB, Graff C, Rasmussen PV, et al. Risk prediction of cardiovascular death based on the QTc interval: evaluating age and gender differences in a large primary care population. European Heart Journal. Mar. 2014; 35 (20): 1335-1344. https://academic.oup.com/eurheartj/article/35/20/1335/430311?login=false
- Kinoshita T MD, Asai T MD PhD, Suzuki T MD PhD, et al. Time course and prognostic implications of QT interval in patients with coronary artery disease undergoing coronary bypass surgery. Journal of Cardiovascular Electrophysiology. Apr. 2012; 23 (6): 645-649. https://onlinelibrary.wiley.com/doi/10.1111/j.1540-8167.2011.02244.x
- Brouillette J, Cyr S, Fiset C. Mechanisms of arrythmia and sudden cardiac death in patients with HIV infection. Canadian Cardiovascular Society. March 2019; 35 (3): 310-319. https://pubmed.ncbi.nlm.nih.gov/30825952/
- Sani MU, Okeahialam BN. QTc interval prolongation in patients with HIV and AIDS. Journal of the National Medical Association. Dec. 2005; 97 (12): 1657-1661. https://pubmed.ncbi.nlm.nih.gov/16396057/#:~:text=Forty%2Dfive%20percent%20of%20the,and%20the%20two%20control%20groups.
Dr. Payal Kohli, MD, FACC is a top graduate of MIT and Harvard Medical School (magna cum laude) and, as a practicing noninvasive cardiologist, is the managing partner of Cherry Creek Heart in Denver, Colorado.
The opinions, beliefs and viewpoints expressed in this article are solely those of the author and do not necessarily reflect the opinions, beliefs and viewpoints of GE Healthcare. The author is a paid consultant for GE Healthcare and was compensated for creation of this article.