QRS fragmentation on electrocardiogram (ECG) is a proposed risk factor for mortality in adults with repaired tetralogy of Fallot (TOF). This study evaluated whether QRS fragmentation could predict mortality in a different population of 465 adults with repaired TOF. The presence and severity of QRS fragmentation on baseline ECG was assessed. Over a mean follow up of 13.6 years, 55 deaths occurred. Moderate to severe QRS fragmentation was associated with a 2-fold increase in risk of all-cause mortality and reduced 20-year survival compared to those without or with only mild fragmentation. QRS fragmentation may serve as a simple, non-invasive marker of risk from routine ECGs in annual follow

1. Journal Club
Murtaza Kamal
18/04/2019

2. Role of QRS fragmentation for risk
stratification in adults with TOF
J Am Heart Assoc., Nov 2018

3. Introduction
• Adults with repaired TOF—> Reduced survival compared to general
population
• 30 yrs survival: 85-90%
• Risk stratification imp—> To identify+ treat patients with high risk of
CV death
• 2. Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, McGoon DC,Kirklin JW, Danielson GK. Long-term outcome in patients undergoing surgicalrepair of tetralogy
of Fallot. N Engl J Med. 1993;329:593–599.
3. Valente AM, Gauvreau K, Assenza GE, Babu-Narayan SV, Schreier J, GatzoulisMA, Groenink M, Inuzuka R, Kilner PJ, Koyak Z, Landzberg MJ, Mulder B, Powell
AJ, Wald R, Geva T. Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled
in the INDICATOR cohort. Heart. 2014;100:247–253.
4. Nollert G, Fischlein T, Bouterwek S, Bohmer C, Klinner W, Reichart B. Longterm survival in patients with repair of tetralogy of Fallot: 36-year follow-up of490 survivors of the first
year after surgical repair. J Am Coll Cardiol.1997;30:1374–1383.
5. Katz NM, Blackstone EH, Kirklin JW, Pacifico AD, Bargeron LM Jr. Late survival and symptoms after repair of tetralogy of Fallot. Circulation. 1982;65:
403–410.

4. Intro cont…
• Proposed risk factors for mortality in aduts with repaired TOF:
• Age at time of repair
• LV/ RV dysfunction
• RV fibrosis/ RVH
• Ventricular arrhythmias
• Increased LVEDP

5. Intro cont…
• Available risk scores includes variables from CMR/ Cardiac cath—> Not
routinely performed during annual evaluation
• ECG: Inexpensive/ Non invasive/ Readily available/ Routinely
performed during annual examination
• 2017: Bokma et al: QRS-f reliably predicts mortality in this population
• Bokma JP, Winter MM, Vehmeijer JT, Vliegen HW, van Dijk AP, van Melle JP,Meijboom FJ, Post MC, Zwinderman AH, Mulder BJ, Bouma BJ. QRSfragmentation is superior to QRS
duration in predicting mortality in adultswith tetralogy of Fallot. Heart. 2017;103:666–671.

6. Aim of study…
• To determine whether QRS-f derived from a standard 12 leads ECG
could independently predict mortality in a different population of
adults with TOF

7. Patient selection…
• Mayo adult CHD database
• > 18 y, repaired TOF
• At least 1 ECG b/w 1/1/1990 to 31/12/2017 (28 y)
• PA: Excluded

8. Data collection…
• Clinical notes/ ECG/ Holter/ ECHO/ Exercise test/ Surgical records/
CMR—> Reviewed
• 1st ECG during study period: Baseline—> Used for assessment of QRS-f
• Clinical data obtained within 12 months of baseline ECG—> Baseline
characteristics
• ECGs analysed by 2 observers: NM/ MF—> Blinded—> If discordance—>
3rd assesses AD

9. QRS-f
• If QRS duration < 120 ms:
• An additional R wave (R’) or notch in nadir of S in ≥ 2 contagious leads
• Rt sided/ septal: aVR, V1, V2
• Anterior: V2-V5
• Lateral: I, aVL, V5, V6
• Inferior: II, III, aVF
• In pts with RBBB:
• ≥ 3 R waves/ notes in R/S complexes in ≥2 contiguous leads
• In pts with paced QRS+ PVC:
• ≥ 3 notches in the R/S complexes

10. QRS-f

11. QRS-f Severity
• No of leads with QRS-f:
• NONE
• MILD: ≤ 3 leads
• MODERATE: 4 leads
• SEVERE: ≥5 leads
• For assessment of progression of QRS-f: Review of ECGs in its with at
least 5 years of follow up

12. Results
• 465 pts
• Age at time of baseline ECG: 37 ± 14y
• 223 (48%): Men
• 41 (9%): Pacemakers
• 58 (13%): Defibrillators
• 100 (22%): H/o VT

15. ECG
• Baseline ECG rhythm:
• Sinus: 407 (88%)
• Atrial flutter/ tachycardia: 20 (4%)
• Atrial and/ or ventricular paced rhythm: 21 (5%)
• HR: 74 ± 9bpm
• QRS duration: 148± 33ms
• QRS morphology:
• Normal: 9 (2%)
• iRBBB: 102 (22%)
• RBBB: 354 (76%)

16. ECG cont…
• QRS-f: 161 (35%)
• Mild: 43 (9%)
• Moderate: 77(17%)
• Severe: 41 (9%)
• Pts with QRS-f:
• Had longer QRS durations: 167±31 vs 126±24 ms, p=0.001
• Were older at time of repair: 7±6 vs 4±3y, p=0.023
• 371 (80%): ECG at 5 y follow up
• 39 (11%): Progression of QRS-f (No—> Mild: 34; Mild —>
MODERATE: 5)

17. Outcomes
• 55 deaths: 12%; Follow up period: 13.6±8.2 y
• CHF: 13 (24%)
• Arrhythmic/ sudden death: 11 (20%)
• Post op death after cardiac sx: 3 (6%)
• MODS by sepsis:4 (7%)
• Malignancy: 5 (9%)
• GI bleed: 1 (2%)
• Stroke: 2 (4%)
• Unknown/ Mixed: 16 (29%)

18. Outcomes cont…
• 20 yrs survival:
• Group without QRS-f: 97%
• Mild QRS-f: 93%; p=0.643
• Moderate QRS-f: 82%; p=0.031
• Severe QRS-f: 33%; p<0.001
• Severity of QRS-f: An independent predictor for all cause
mortality after adjustment for other ECG parameters, pt
demographics, vent. Function and h/o atrial/ ventricular arrhythmias

19. Discussion
• QRS duration> 180 ms: Risk factor of sudden death
• Bokma et al: QRS-f superior in prediction of all cause mortality
• This study: In a different population (US vs Dutch)
• Moderate/ severe QRS-f: 2 fold increase in risk of all cause mortality,
had reduced 20y survival

20. QRS-f as a marker of
ventricular dysfunction
• Studies with QRS-f of lt precordial leads—> Associated with
myocardial scar + LV aneurysm in its with CAD (Severity co-relates
with extent of scar)
• QRS-f in anterior leads—> Associated with RV dysfunction+ RVOT
aneurysm in TOF pts
• A marker of myocardial fibrosis—> LGE in CMR
• Das MK, Khan B, Jacob S, Kumar A, Mahenthiran J. Significance of a fragmented QRS complex versus a Q wave in patients with coronary arterydisease. Circulation.
2006;113:2495–2501.
14. Reddy CV, Cheriparambill K, Saul B, Makan M, Kassotis J, Kumar A, Das MK.Fragmented left sided QRS in absence of bundle branch block: sign of leftventricular aneurysm. Ann Noninvasive
Electrocardiol. 2006;11:132–138.
15. Shanmugam N, Yap J, Tan RS, Le TT, Gao F, Chan JX, Chong D, Ho KL, Tan BY,Ching CK, Teo WS, Tan JL, Liew R. Fragmented QRS complexes predict rightventricular dysfunction and
outflow tract aneurysms in patients with repaired tetralogy of Fallot. Int J Cardiol. 2013;167:1366–1372.
16. Park SJ, On YK, Kim JS, Park SW, Yang JH, Jun TG, Kang IS, Lee HJ, Choe YH,Huh J. Relation of fragmented QRS complex to right ventricular fibrosis
detected by late gadolinium enhancement cardiac magnetic resonance in adults with repaired tetralogy of fallot. Am J Cardiol. 2012;109:110–115.

21. Myocardial fibrosis/ scar
• Known to occur in repaired TOF—> RV dysfunction/ poor CV outcomes—
> HF/ arrhythmias/ death
• Deterioration in myocardial contraction+ relaxation—> Substrate for
arrhythmias
• CMR important in risk stratification
• QRS-f: A surrogate for myocardial fibrosis, predictive of all cause
mortality
• Bokma et al —> Had older pts with more co-morbidities—> Higher all
cause mortality (6 vs 12%)
• Good inter observer correlation—> Technique can be easily integrated
in daily clinical practice

22. Inter observer correlation

23. Clinical impact
• Several risk scores: Good predictive value in population from which
derived
• CMR/ cat: Not performed annually
• Annual evaluation needed: Risk changes over time
• ECG: Inexpensive/ available/ recommended as a part of routine
evaluation

24. Limitations
• Usage of all cause mortality instead of CV mortality as primary end
point
• If QRS-f postulated to be caused by myocardial fibrosis, vent
dysfunction+ arrhythmias—> Then, shud predict cv mortality without
much association with non cardiovascular mortality
• No correction was made for length of time each pt had QRS-f before
initial ECG—> Lead time bias

25. Conclusions
• Assessment of presence+ severity of QRS-f feasible in all pts—>
Reproduccible with good IO correlation, independently predictive of all
cause mortality
• ECG: Inexpensive/ easy to interpret/ available/ routinely obtained
• QRS-f: Readily available risk stratification for these pts, may be
complementary to existing risk scores

26. Food for further thinking…
• To evaluate temporal changes in extent of QRS-f
• If timely interventions based on these changes will improve outcomes

27. THANKZ…