Hostname: page-component-74656f9884-2dmjx Total loading time: 0 Render date: 2026-11-06T12:58:25.842Z Has data issue: false hasContentIssue false
  • English
  • Français

Lower spatial QRS-T angle rules out sustained ventricular arrhythmias in children with hypertrophic cardiomyopathy

Published online by Cambridge University Press:  01 June 2016

Daniel Cortez ,
Nandita Sharma ,
Jean Cavanaugh ,
Froilan Tuozo ,
Gwendolyn Derk ,
Emily Lundberg ,
Keith Weiner ,
Nafiz Kiciman ,
Juan Alejos  and
Bruce Landeck
...Show all authors
Daniel Cortez*
Affiliation:
Children’s Hospital Colorado/University of Colorado, Aurora, Colorado, United States of America Department of Cardiovascular Sciences, Lund University, Lund, Sweden
Nandita Sharma
Affiliation:
Penn State Milton Hershey Medical Center, Hershey, Pennsylvania, United States of America
Jean Cavanaugh
Affiliation:
Children’s Hospital Colorado/University of Colorado, Aurora, Colorado, United States of America
Froilan Tuozo
Affiliation:
University of California at Irvine, Irvine, California, United States of America
Gwendolyn Derk
Affiliation:
University of Illinois College of Medicine, Champaign-Urbana, United States of America
Emily Lundberg
Affiliation:
University of California, Los Angeles, United States of America
Keith Weiner
Affiliation:
CHOC Children’s, Orange, California, United States of America
Nafiz Kiciman
Affiliation:
University of California at Irvine, Irvine, California, United States of America
Juan Alejos
Affiliation:
University of California, Los Angeles, United States of America
Bruce Landeck
Affiliation:
Children’s Hospital Colorado/University of Colorado, Aurora, Colorado, United States of America
Jamil Aboulhosn
Affiliation:
University of Illinois College of Medicine, Champaign-Urbana, United States of America
Shelley Miyamoto
Affiliation:
Children’s Hospital Colorado/University of Colorado, Aurora, Colorado, United States of America
Anthony C. McCanta
Affiliation:
CHOC Children’s, Orange, California, United States of America
Anjan S. Batra
Affiliation:
University of California at Irvine, Irvine, California, United States of America
*
Correspondence to: D. Cortez, MD, 13123 East 16th Avenue, Box 100, Aurora, Colorado 80045, United States of America. Tel: +303 718 6871; Fax: +720 777 7290; E-mail: Dr.danielcortez@gmail.com
Rights & Permissions [Opens in a new window]

Abstract

Introduction

The spatial peaks QRS-T angle accurately distinguishes children with hypertrophic cardiomyopathy from their healthy counterparts. The spatial peaks QRS-T angle is also useful in risk stratification for ventricular arrhythmias. We hypothesised that the spatial peaks QRS-T angle would be useful for the prediction of ventricular arrhythmias in hypertrophic cardiomyopathy patients under 23 years of age.

Methods

Corrected QT interval and spatial peaks QRS-T angles were retrospectively assessed in 133 paediatric hypertrophic cardiomyopathy patients (12.4±6.6 years) with versus without ventricular arrhythmias of 30 seconds or longer. Significance, positive/negative predictive values, and odds ratios were calculated based on receiver operating characteristic curve cut-off values.

Results

In total, 10 patients with ventricular arrhythmias were identified. Although the corrected QT interval did not differentiate those with versus without ventricular arrhythmias, the spatial peaks QRS-T angle did (151.4±19.0 versus 116.8±42.6 degrees, respectively, p<0.001). At an optimal cut-off value (124.1 degrees), the positive and negative predictive values of the spatial peaks QRS-T angle were 15.4 and 100.0%, respectively, with an odds ratio of 25.9 (95% CI 1.5–452.2).

Conclusion

In children with hypertrophic cardiomyopathy, the spatial peaks QRS-T angle is associated with ventricular arrhythmia burden with high negative predictive value and odds ratio.

Keywords

Spatial QRS-T angleventricular arrhythmiaspredictionhypertrophic cardiomyopathyQTc

Information

Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 2 , March 2017 , pp. 354 - 358
Check for updates
Copyright
© Cambridge University Press 2016 

Hypertrophic cardiomyopathy has an estimated prevalence of 1 in 500. The phenotype can include thickened ventricular walls, with or without obstruction of blood flow at the left ventricular outflow tract, increased risk of progression to NYHA III/IV functional class, and increased risk of arrhythmia-induced sudden cardiac death in both adults and paediatric-aged patients.Reference Olivotto, Girolami and Ackerman 1 – Reference Elliott, Poloniecki and Dickie 3

Vectorcardiography is a method of recording the direction and magnitude of electrical forces generated by the heart by means of a series of continuous vectors. The method most frequently utilised was developed by Dr Ernest Frank and is chosen because of its ease of application and theoretical soundness.Reference Frank 4 Recent advances in electrocardiographic technology, including the ability to automatically transform digital 12-lead ECG data into orthogonal vectorcardiographic data,Reference Kors, van Herpen and Sittig 5 can add further diagnosticReference Dilaveris, Gialafos and Pantazis 6 – Reference Voulgari, Tentolouris and Moyssakis 8 and prognosticReference Borleffs, Scherptong and Man 9 – Reference Yamazaki, Froelicher and Myers 17 utility to traditional 12-lead electrocardiograms. Among the derived vectorcardiographic parameters obtainable after such transformations, the spatial QRS-T angle has notable diagnostic utility for conditions in which sudden death may be an outcome,Reference de Torbal, Kors and van Herpen 10 , Reference Kardys, Kors and van der Meer 11 , Reference Rautaharju, Kooperberg and Larson 15 , Reference Yamazaki, Froelicher and Myers 17 in both adultReference Poplock Potter, Holvqvist and Platonov 18 and paediatricReference Cortez, Sharma and Cavanaugh 19 hypertrophic cardiomyopathy patients. The spatial QRS-T angle has also been positively correlated with risk for ventricular arrhythmia in adult patients with ischaemic heart disease.Reference Borleffs, Scherptong and Man 9 We hypothesised that the spatial QRS-T angle would be useful for identification of ventricular arrhythmias in paediatric hypertrophic cardiomyopathy patients under 23 years of age.

Methods

We retrospectively reviewed 12-lead electrocardiograms of paediatric patients <23 years of age with hypertrophic cardiomyopathy during routine follow-up visits to clinics at Children’s Hospital of Colorado, CHOC Children’s, and the University of California at Los Angeles. The overall cohort, apart from the three additional hypertrophic cardiomyopathy patients with ventricular arrhythmias who met the criteria described, and methods of obtaining electrocardiograms as well as echocardiographic measures have been previously described.Reference Cortez, Sharma and Cavanaugh 19 Institutional review board approval from each institution was obtained. This age group was chosen because in the United States of America it represents most patients of collegiate age or younger, where organisation of screening is typically more accessible. It also represents a large number of patients that the American Heart Association includes in its recent statement regarding electrocardiogram screening.Reference Maron, Friedman and Kligfield 20 The diagnosis of hypertrophic cardiomyopathy was based on an echocardiographic evidence of diastolic dysfunction and a Boston z-score of ⩾2.5 for posterior wall or septal thickness during diastole measured from a parasternal short-axis view with left ventricular end-diastolic diameter of 45 mm or, for purely apical hypertrophic cardiomyopathy (n=3), a qualitative interpretation by the reading cardiologist of significant apical thickness with the same end-diastolic diameter cut-off value.

Parameters

Electrocardiograms were obtained at 25 mm/s speed with 10 mm/mV for the limb and praecordial leads. Corrected QT interval and spatial peaks QRS-T angles were assessed. Patients with history of sustained ventricular arrhythmias (30 seconds or greater) by Holter monitoring, exercise stress test, implantable cardiac defibrillator, or a pacemaker within 6 months before the electrocardiogram recording were compared with those without history of sustained ventricular arrhythmias. The vectorcardiographic spatial peaks QRS-T angle was visually derived from conventional 12-lead electrocardiogram recordings based on the method recently described by Cortez et al,Reference Cortez, Sharma and Devers 21 utilising the regression-related transform of Kors et al.Reference Dilaveris, Gialafos and Pantazis 6

Statistics

Student’s T-test and the Mann–Whitney U-test were used as appropriate to evaluate differences between hypertrophic cardiomyopathy patients with versus without ventricular arrhythmias. A p-value of 0.05 or less was deemed significant. Odds ratios were also calculated for each of the above-mentioned criteria based on receiver operating characteristic curve analyses. R-values from regression line analysis were obtained for significant parameters. Multivariate analysis was performed to assess independent predictors. All statistical analyses were performed on PSPP (Pfaff, J. Darrington et al GNU PSPP. http://www.gnu.org/software/pspp/).

Results

Patient population

Electrocardiographic results from 133 hypertrophic cardiomyopathy patients (12.4±6.6 years) were assessed; 10 patients with ventricular arrhythmias (five with ICD’s) were identified (12.1±7.9 years, 90.0% males), compared with 123 patients without ventricular arrhythmias (12.4±6.7 years, 70.4% males) (Table 1). Age, male sex, septal thickness, nor septal thickness z-score differentiated those with ventricular arrhythmias from those without ventricular arrhythmias (Table 1). Out of patients with ventricular arrhythmias, one had Noonan syndrome and one had Leopard syndrome. Out of those without ventricular arrhythmias, six patients had Noonan syndrome and one had Danon disease. Owing to the limited number of patients, assessment of differences between the above syndromes was not performed.

Table 1

Patient demographics and results for hypertrophic cardiomyopathy patients with versus without sustained ventricular arrhythmias (VA and no VA, respectively).

Parameters assessed include age, sex, bundle branch blocks, septal thickness in centimetres and z-score, left ventricular outflow tract obstruction (LVOT obstruction, number), corrected QT interval (QTc in milliseconds, ms), and the spatial peaks QRS-T angle (SPQRS-T angle in degrees)

Corrected QT interval

The corrected QT interval did not differentiate those paediatric-aged hypertrophic cardiomyopathy patients with versus without ventricular arrhythmias (p=0.678). Only four of the 10 hypertrophic cardiomyopathy patients with ventricular arrhythmias (40.0%) had corrected QT interval values >460 ms, whereas 38/123 hypertrophic cardiomyopathy patients without ventricular arrhythmias (30.9%) had corrected QT interval values >460 ms (p=0.725). Post-hoc power calculation gave a power of 20.0%.

Spatial peaks QRS-T angle

The spatial peaks QRS-T angle differentiated those with versus without ventricular arrhythmias (151.4±19.0 versus 116.8±42.6 degrees, respectively, p<0.001). At an optimum cut-off value of 124.1 degrees, derived from receiver operating characteristic curve analysis optimum cut-off point (see Fig 2), the positive predictive value and negative predictive value were 15.4 and 100.0%, respectively, with an odds ratio of 25.9 (95% confidence interval 1.5–452.2). The area under the receiver operating characteristic curve was 0.74 (95% confidence interval 0.64–0.84, Fig 1). When multivariate analysis was performed using logistic regression, the spatial peaks QRS-T angle was the only independent predictor of ventricular arrhythmias in children with hypertrophic cardiomyopathy when sex, bundle branch blocks, absolute septal thickness z-score, and QTc were taken into account (p=0.011). Of the 10 patients with ventricular arrhythmias, two had complete left bundle branch blocks, whereas 4/123 patients without ventricular arrhythmias had complete bundle branch blocks (p=0.065); however, when only those without complete bundle branch blocks were compared, a significant difference in the spatial peaks QRS-T angle still existed between paediatric-aged hypertrophic cardiomyopathy patients with sustainable ventricular arrhythmias versus those without it (p<0.001). The R-value for the spatial peaks QRS-T angle and maximum septal thickness z-score was 0.61.

Figure 1

Area under the receiver operating characteristic curve (0.74 with 95% confidence intervals of 0.64–0.84) for the spatial QRS-T angle for comparisons of paediatric-aged hypertrophic cardiomyopathy patients with versus those without sustainable ventricular arrhythmias.

Discussion

The most important finding from this study was that the spatial peaks QRS-T angle significantly differentiated paediatric-aged hypertrophic cardiomyopathy patients with ventricular arrhythmias from those without ventricular arrhythmias, while the corrected QT interval did not.

Corrected QT interval

Corrected QT interval prolongation has been previously described in hypertrophic cardiomyopathy patients, with 13% described as having values >480 ms.Reference Johnson, Grifoni and Bos 22 An association between a prolonged QT interval, specifically greater than 460 ms, and ventricular arrhythmias, as well as sudden cardiac death in hypertrophic cardiomyopathy, has also been described.Reference Debonnaire, Katsanos and Joyce 23 In our paediatric cohort, the corrected QT interval was not significantly different between hypertrophic cardiomyopathy patients with versus without ventricular arrhythmias, nor did a corrected QT interval at a cut-off value of 460 ms predict ventricular arrhythmias; however, the post-hoc power calculation demonstrated possibly insufficient numbers to prevent a Type 2 error in QTc comparison. Another reason more patients were likely needed is that this population represents younger patients, and thus less variability in the QTc, as it does increase with age and likely has a greater difference in effect on adult patients than paediatric-aged patients.Reference Rijnbeek, van Herpen and Bots 24

Spatial QRS-T angle

Increased spatial peaks QRS-T angle has previously been shown to identify patients with hypertrophic cardiomyopathyReference Poplock Potter, Holvqvist and Platonov 18 , Reference Cortez, Sharma and Cavanaugh 19 and to predict ventricular arrhythmias in adults with myocardial ischaemia.Reference Borleffs, Scherptong and Man 9 Thus, it seems logical that increased spatial peaks QRS-T angle might also predict ventricular arrhythmias in patients with hypertrophic cardiomyopathy. As the spatial peaks QRS-T angle also increases with degree of hypertrophy, with an R-value of 0.61, it seems logical it would also identify patients with ventricular arrhythmias.Reference Cortez, Sharma and Cavanaugh 19 Furthermore, given the number of males in this study, male sex was used in the multivariate analysis, which shows that, regardless of sex, BBB, absolute septal thickness Z-score, or QTc, the SPQRS-T angle was still an independent predictor ventricular arrhythmias. The poor positive predictive value may be explained by the degree of myocardial disorganisation or scarring; however, as most patients were diagnosed by echocardiography, insufficient data – lack of MRI measurements – were present to investigate this further.

The spatial peaks QRS-T angle significantly differentiated hypertrophic cardiomyopathy patients with versus without ventricular arrhythmias when patients with bundle branch blocks were excluded. Similar to heart failure patient identification in adult studies, bundle branch blocks did not affect the diagnostic utility of the spatial peaks QRS-T angle in our current assessment; thus, this is again another example where the spatial peaks QRS-T angle identification ability is not sufficiently affected by bundle branch blocks.Reference Zhang, Rautaharju and Prineas 25

The spatial peaks QRS-T angle has been previously reported to be higher in paediatric-aged hypertrophic cardiomyopathy patients with Noonan syndrome, Leopard syndrome, Danon disease, and those with genotype positivity as compared with other paediatric-aged hypertrophic cardiomyopathy patients, and we report that it is also higher in those with ventricular arrhythmias; thus, increased spatial peaks QRS-T angle likely represents a marker of sudden death risk.Reference Cortez, Sharma and Cavanaugh 26 This is similar to what has been demonstrated in other patient populations.Reference Triola, Olson and Reis 7 – Reference Yamazaki, Froelicher and Myers 17

The spatial peaks QRS-T angle, although not associated with maximum thickness, did show an association with maximum thickness z-scores, which is the first time this has been demonstrated. Given the paediatric population and the SPQRS-T angle’s association with ventricular arrhythmias – a risk for sudden death in hypertrophic cardiomyopathy – it seems that the association with maximum thickness z-score – another risk factor for sudden death in hypertrophic cardiomyopathy – seems reasonable.

Limitations

This study had certain limitations including the size of the paediatric-aged hypertrophic cardiomyopathy group. This was also a retrospective study, and thus not prospective in nature as would be needed to validate this method.

Conclusion

In our cohort of paediatric-aged hypertrophic cardiomyopathy patients, the SPQRS-T angle was significantly associated with ventricular arrhythmias with high negative predictive value and odds ratio, while the QTc was not. There was also a significant association of the spatial peaks QTS-T angle with septal thickness z-score. Further prospective studies are needed to assess the future predictive value of a large spatial QRS-T angle in paediatric-aged hypertrophic cardiomyopathy patients (Fig 2).

Figure 2

Spatial peaks QRS-T angle (angles) for hypertrophic cardiomyopathy patients with sustained ventricular arrhythmias (VA) and those without VA. p-value is <0.001, which gives a significant difference between the patients.

Acknowledgements

None.

Financial Support

The research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Conflicts of Interest

None.

References

1. Olivotto, I, Girolami, F, Ackerman, MJ, et al. Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clinic Proceedings 2008; 83: 630–638.Google Scholar
2. Spirito, P, Autore, C, Rapezzi, C, et al. Syncope and risk of sudden death in hypertrophic cardiomyopathy. Circulation 2009; 119: 1703–1710.Google Scholar
3. Elliott, PM, Poloniecki, J, Dickie, S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36: 2212–2218.Google Scholar
4. Frank, E. An accurate, clinically practical system for spatial vectorcardiography. Circulation 1956; 13: 731–749.Google Scholar
5. Kors, JA, van Herpen, G, Sittig, AC, et al. Reconstruction of the Frank vectorcardiogram from standard electrocardiographic leads: diagnostic comparison of different methods. Eur Heart J 1990; 11: 1083–1092.Google Scholar
6. Dilaveris, P, Gialafos, E, Pantazis, A, et al. The spatial QRS-T angle as a marker of ventricular repolarisation in hypertension. J Hum Hypertens 2001; 15: 63–70.CrossRefGoogle ScholarPubMed
7. Triola, B, Olson, MB, Reis, SE, et al. Electrocardiographic predictors of cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol 2005; 46: 51–56.Google Scholar
8. Voulgari, C, Tentolouris, N, Moyssakis, I, et al. Spatial QRS-T angle: association withdiabetes and left ventricular performance. Eur J Clin Invest 2006; 36: 608–613.CrossRefGoogle Scholar
9. Borleffs, CJ, Scherptong, RW, Man, SC, et al. Predicting ventricular arrhythmias in patients with ischemic heart disease: clinical application of the ECG-derived QRS-T angle. Circ Arrhythm Electrophysiol 2009; 2: 548–554.Google Scholar
10. de Torbal, A, Kors, JA, van Herpen, G, et al. The electrical T-axis and the spatial QRS-Tangle are independent predictors of long-term mortality in patients admitted with acute ischemic chestpain. Cardiology 2004; 101: 199–207.Google Scholar
11. Kardys, I, Kors, JA, van der Meer, IM, et al. Spatial QRS-T angle predicts cardiac death in a general population. Eur Heart J 2003; 24: 1357–1364.CrossRefGoogle ScholarPubMed
12. Kors, JA, Kardys, I, van der Meer, IM, et al. Spatial QRS-T angle as a risk indicator of cardiac death in an elderly population. J Electrocardiol 2003; 36 (Suppl): 113–114.Google Scholar
13. Rautaharju, PM, Ge, S, Nelson, JC, et al. Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study). Am J Cardiol 2006; 97: 309–315.Google Scholar
14. Rautaharju, PM, Kooperberg, C, Larson, JC, et al. Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: the Women’sHealth Initiative. Circulation 2006; 113: 481–489.Google Scholar
15. Rautaharju, PM, Kooperberg, C, Larson, JC, et al. Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women’s Health Initiative. Circulation 2006; 113: 473–480.CrossRefGoogle ScholarPubMed
16. Rautaharju, PM, Prineas, RJ, Wood, J, et al. Electrocardiographicpredictors of new-onset heart failure in men and in women free of coronary heart disease (from the Atherosclerosis in Communities [ARIC] Study). Am J Cardiol 2007; 100: 1437–1441.Google Scholar
17. Yamazaki, T, Froelicher, VF, Myers, J, et al. Spatial QRS-T angle predicts cardiac death in a clinical population. Heart Rhythm 2005; 2: 73–78.Google Scholar
18. Poplock Potter, SL, Holvqvist, F, Platonov, PG, et al. Detection of hypertrophic cardiomyopathy is improved when using advanced rather than strictly conventional 12-electrocardiogram. J Electrocardiol 2010; 43: 713–718.Google Scholar
19. Cortez, D, Sharma, N, Cavanaugh, J, et al. The spatial QRS-T angle outperforms the Italian and Seattle ECG-based criteria for detection of hypertrophic cardiomyopathy in pediatric patients. J Electrocardiol 2015; 48: 826–833.Google Scholar
20. Maron, BJ, Friedman, RA, Kligfield, P, et al. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12–25 years of age). A scientific statement from the American Heart Association and the American College of Cardiology. JACC 2014; 64: 1479–1514.Google Scholar
21. Cortez, D, Sharma, N, Devers, C, et al. Visual transform applications for estimating the spatial QRS-T angle from the conventional 12-lead ECG: Kors is still most Frank. J Electrocardiol 2014; 47: 12–19.CrossRefGoogle ScholarPubMed
22. Johnson, JN, Grifoni, C, Bos, JM, et al. Prevalence and clinical correlates of QT prolongation in patients with hypertrophic cardiomyopathy. Eur Heart J 2011; 32: 1114.Google Scholar
23. Debonnaire, P, Katsanos, S, Joyce, E, et al. QRS fragmentation and QTc duration relate to malignant ventricular tachycarrhythmias and sudden cardiac death in patients with hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 2015; 26: 547–555.Google Scholar
24. Rijnbeek, PR, van Herpen, G, Bots, ML, et al. Normal values of the electrocardiogram for ages 16-90 years. Journal of Electrocardiology 2014; 47: 914–921.CrossRefGoogle ScholarPubMed
25. Zhang, ZM, Rautaharju, PM, Prineas, RJ, et al. Usefulness of electrocardiographic QRS-T angles with versus without bundle branch blocks to predict heart failure (from the Atherosclerosis Risk in Communities Study). Am J Cardiol 2014; 114: 412–418.Google Scholar
26. Cortez, D, Sharma, N, Cavanaugh, J, et al. The spatial QRS-T angle outperforms the Italian and Seattle ECG-based criteria for detection of hypertrophic cardiomyopathy in pediatric patients. J Electrocardiol 2015; 48: 826–833.Google Scholar
Figure 0

Table 1 Patient demographics and results for hypertrophic cardiomyopathy patients with versus without sustained ventricular arrhythmias (VA and no VA, respectively).

Figure 1

Figure 1 Area under the receiver operating characteristic curve (0.74 with 95% confidence intervals of 0.64–0.84) for the spatial QRS-T angle for comparisons of paediatric-aged hypertrophic cardiomyopathy patients with versus those without sustainable ventricular arrhythmias.

Figure 2

Figure 2 Spatial peaks QRS-T angle (angles) for hypertrophic cardiomyopathy patients with sustained ventricular arrhythmias (VA) and those without VA. p-value is <0.001, which gives a significant difference between the patients.