Elsevier

International Journal of Cardiology

Volume 323, 15 January 2021, Pages 34-39
International Journal of Cardiology

Left ventricular strain and fibrosis in adults with repaired tetralogy of Fallot: A case-control study

https://doi.org/10.1016/j.ijcard.2020.08.092Get rights and content

Highlights

  • LV 2D and 3D GCS and GLS were lower in rTOF subjects compared to age-matched healthy subjects.

  • There was no association between LV strain and LV-ECV.

  • GLS was an independent predictor of hospitalization and death; LV-ECV was an independent predictor of arrhythmia.

  • Our findings suggest that LV strain ad LV-ECV reflect different long-term adverse adaptations to abnormal hemodynamics.

Abstract

Background

Left ventricular (LV) systolic dysfunction and myocardial fibrosis have prognostic implications in repaired tetralogy of Fallot (rTOF), but their relationship with myocardial strain is not well understood. We evaluated systolic strain and fibrosis (extracellular volume fraction, ECV) of the left ventricle (LV) using feature tracking with magnetic resonance and determine their association with each other and clinical outcome.

Method

Adults with rTOF and age-matched controls underwent CMR to measure LV-ECV. Feature-tracking was used to quantify radial, circumferential, and longitudinal strain in both 2 and 3 dimensions. Clinical events (death, arrhythmia and heart-failure hospitalization) were obtained through chart review. Associations between strain, ECV and clinical events were explored.

Results

48 rTOF subjects (age 40.5 ± 14.3, 42% female) and 20 healthy controls were included. Both LV 2D and 3D global circumferential strain (GCS) and global longitudinal strain (GLS) were lower in rTOF subjects (p ≤0.01 for all). There was no association between strain and LV-ECV. Strain parameters correlated with ventricular volumes and function. After a median follow-up of 8.5 years (range 1–10.9 years) there were 5 deaths, 6 hospitalizations and 9 new arrhythmias. By multivariate Cox-regression, GLS was an independent predictor of both hospitalization and death, whereas LV-ECV was an independent predictor of arrhythmia.

Conclusion

While both LV strain abnormalities and fibrosis are present in rTOF, they are associated with different types of clinical outcome, and not to each other. The findings suggest that these measures reflect different long-term adverse adaptations to abnormal hemodynamics.

Introduction

Long-term follow-up of repaired tetralogy of Fallot (rTOF), the most common form of cyanotic congenital heart disease in adults [1], is typically focused on right ventricular (RV) systolic and diastolic function. However, left ventricular function (LV) is also a factor contributing to decreased exercise capacity, ventricular arrhythmias, and mortality [[2], [3], [4], [5]]. A plausible explanation is that moderate to severe pulmonary insufficiency creates chronic RV volume load which drives RV dilation and increased RV wall stress, which in turn lead to LV dysfunction via ventricular-ventricular interactions [5]. This process is likely gradual, occurring over many decades.

Cardiac magnetic resonance (CMR) allows for extensive cardiac evaluation including myocardial characterization [6]. RV and LV abnormalities have been associated with adverse clinical markers and outcomes in patients with rTOF across a broad range of ages [[5], [6], [7], [8], [9]]. Myocardial extracellular volume (ECV), a surrogate of diffuse interstitial myocardial fibrosis, can be evaluated by T1 mapping [6]. Increased myocardial fibrosis has been found in patients with tetralogy of Fallot, even at a young age [7,10] and has been associated with abnormal left ventricular mechanics [11].

In addition, CMR-based feature tracking (CMR-FT) assessment of myocardial strain can be used as a measure of both global and regional myocardial function. This method, which can be applied to previously obtained standard cine images, provides quantification of multidimensional myocardial motion, more so than ejection fraction alone [12]. CMR-FT allows for post-processing evaluation of myocardial strain by automatically tracking the epicardial and endocardial borders, as well as their velocities, displacement, strain and strain rate over time [[12], [13], [14]]. Various strain parameters have been used to predict long-term clinical outcomes in acquired heart disease, including ischemic heart disease and dilated cardiomyopathy [[15], [16], [17]]. It's use in rTOF remains limited. We have previously used CMR-FT to demonstrate differences between children with rTOF and healthy peers [18]. CMR-FT has also been applied to the RV and RA in TOF [19]. Because both LV-ECV and strain measures reflect LV myocardial change, and because both have limited association with clinical endpoints, we postulated that the two measures would be associated with one another.

Our primary aim was to determine whether LV myocardial fibrosis measured by T1 mapping is associated with LV systolic strain measured by CMR-FT. Our secondary aim was to determine the association between LV systolic strain and LV-ECV with three major clinical outcomes: death, arrhythmia and hospitalization for heart failure. As this was an exploratory study, all strain metrics were considered, including global radial, circumferential, and longitudinal strain in both 2 and 3 dimensions.

Section snippets

Patient selection

We retrospectively reanalyzed CMR studies from adults with rTOF and healthy subjects without known cardiovascular disease. All patients had previously been enrolled in a prospective study involving CMR at our institution and had signed informed consent to participate [7]. Clinical information about their repair, medications, arrhythmias, and symptoms were previously reported. The study was approved by the institutional review board at Oregon Health & Science University.

Image analysis

Strain analysis was done

Results

Our initial study cohort consisted of 52 rTOF subjects. Upon review, four rTOF subjects did not have adequate quality cine imaging in all views, either because of respiratory artifact or gating issues, to make accurate strain quantifications and were not included. The remaining 48 rTOF subjects constituted our patient cohort (age 40.5, SD = 14.3 years, 42% female) with 20 controls (age 39.4, SD = 11.9, 45% female). Group comparisons are presented in Table 1. As expected, the groups also

Discussion

ECV and myocardial strain have gained wide interest in the last decade as tools for myocardial assessment. Our study confirms that both LV-ECV and global systolic strain are abnormal compared to controls and are associated with cardiac chamber size and function and clinical outcome. Previous studies have shown associations between these measures and clinical events such as arrhythmias, LV systolic and diastolic dysfunction and death, though with some mixed results [[2], [3], [4],[7], [8], [9],

Conclusions

Left ventricular dysfunction is an expected phenomenon after repaired tetralogy of Fallot and has significant prognostic implications. CMR can provide quantification of both myocardial strain analysis and diffuse fibrosis, both of which have associations with other clinical variables and outcomes. However, we found no association between global systolic strain and LV-ECV. The study suggests these metrics are reflective of different pathologic processes and related to different types of outcome.

Funding

Portions of this study were supported by a K23 Career-Development Grant from the National Heart, Lung, and Blood Institute (K23HL093024).

Declaration of competing interest

The authors have no conflicts of interest to disclose.

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All authors take full responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation

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