Modified Ventricular Global Function Index Correlates With Exercise Capacity in Repaired Tetralogy of Fallot

Modified Ventricular Global Function Index Correlates With Exercise Capacity in Repaired Tetralogy of Fallot

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Ta HT, Critser PJ, Alsaied T, Germann J, Powell AW, Redington AN, Tretter JT.

J Am Heart Assoc. 2020 Jul 21;9(14):e016308. doi: 10.1161/JAHA.120.016308. Epub 2020 Jul 7.

PMID: 32633206

Take Home Points:

  • Establishing RV effective Global function index (eGFI) as a novel and more robust predictor of hard clinical end points in patients with rTOF.
  • RV eGFI may be a more comprehensive marker of poor myocardial health and exercise intolerance than currently used indices.
  • The association between reduced RV eGFI with impaired exercise performance establishes biologic plausibility which may form the basis of larger scale studies assessing the value of preoperative eGFI in timing of PVR ,

Dr. Soha Romeih

Commentary by Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:

Despite improvements in early survival in rTOF, there continues to be a high incidence of impaired functional status, heart failure, arrhythmias, and death, which often occur in the setting of RV dysfunction with either volume- and/or pressure-loading of the RV.

To improve these outcomes, PVR is often performed in symptomatic patients or asymptomatic patients who have significant RV dilation or RV systolic dysfunction. However, using current guidelines, PVR does not lead to survival benefit or reduce other major adverse postoperative events.

Recent investigations have shown that preoperative RV hypertrophy and dysfunction, not ventricular volumes, particularly in patients approaching their 3rd decade of life, are associated with worse outcomes—highlighting the importance of maintaining myocardial health.

CMR derived ventricular global function index (GFI), has been proposed as a

better marker of ventricular function because it incorporates structural, mechanical, and preload indices.


Establishing eGFI, or the lesion-specific modification described in the current study, as a novel and more robust predictor of hard clinical end points in patients with rTOF will require prospective testing in a large, likely multi-center, study after biologic plausibility has been established.

To do the latter, this “proof-of-principle” study leverages the known association between impaired exercise capacity as assessed by cardiopulmonary exercise testing (CPET) and poorer outcomes in patients with rTOF.


75 patients with rTOF who underwent CMR were identified. Clinical variables were recorded and biventricular GFI calculated. RV effective GFI (eGFI) was derived by incorporating effective stroke volume. 35 pediatric patients were matched with 29 age-matched healthy controls. 25 patients completed cardiopulmonary exercise tests within 6 months of CMR.

RV effective Global function index

pulmunary regurgitant fraction


Median age at CMR was 20 years (interquartile range, 13–28). Pediatric rTOF patients had lower RV eGFI (P < 0.001), RV-EF (P=0.002), but higher indexed RV EDV and ESV (P < 0.001, P < 0.001) compared with controls.

Univariate analysis demonstrated a correlation between indexed peak VO2 with RV eGFI (R2=0.32, P=0.004), but with neither RVGFI, RV ejection fraction, indexed RV volumes nor RV mass.  RV eGFI remained significantly associated with indexed peak VO2 during multivariable modeling


This study demonstrates that the novel modification of the GFI, incorporating effective stroke volume rather than total stroke volume (eGFI), may be a useful non-invasive method to assess myocardial health in patients with rTOF.

Reduced RV eGFI was associated with impaired exercise capacity in patients with rTOF, while RV EF, RV GFI using the total RV stroke volume, indexed RV volumes and mass were not.

While preoperative RV volumes and EF are the most commonly used indices to determine the need for PVR in asymptomatic patients, their optimal thresholds continue to be debated, and they do not appear to be related to hard clinical end points such as death, heart failure or ventricular tachycardia after PVR.

Patients had significantly lower RV function as measured by both RV EF and RV eGFI values compared with controls. Importantly, in multivariate analysis, RV eGFI but neither RV GFI, RV EF, nor RV volume indices was correlated with exercise performance.

Those finding of an association between reduced RV eGFI with impaired exercise performance is important for 2 reasons—first, impaired exercise performance correlates with poor outcomes; and second, this establishes biologic plausibility may form the basis of larger scale studies of the value of preoperative GFI in defining potential thresholds for PVR and predicting outcomes thereafter.

This data disagrees somewhat with the findings of Rashid and colleagues who evaluated a larger cohort of similarly aged patients with rTOF who underwent CPET and CMR. Similar to current findings, RV size did not correlate with peak VO2 in their study, but indices of RV systolic function including RV EF and stroke volume index did correlate significantly. Of note, patients in current had lower indexed RV volumes and higher RV EF when compared with the study by Rashid and are consistent with a study in younger patients with rTOF that demonstrated only a weak association between RV EF and exercise performance.


There were several limitations to this study including its retrospective nature from a single center.


Patients with rTOF had lower RV eGFI compared with age-matched controls. Reduced RV eGFI was associated with reduced exercise capacity, while RV EF, indexed RV volumes, and mass were not. This supports RV eGFI as a potentially valuable non-invasive marker of cardiac function in the rTOF population.