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Elevated Repolarization Dispersion Linked With LV Diastolic Discoordination in Pediatric PAH

Article

Repolarization dispersion has been linked to echocardiographic measures of diastolic dysfunction in past research, and a recent study found it potentially indicative of pulmonary arterial hypertension severity.

In patients with pulmonary arterial hypertension (PAH), electromechanical dyssynchrony is a well-described comorbidity. However, diastolic dysfunction and electromechanical imaging markers from electrocardiogram (ECG) scans have not been investigated in past research. A recent study published in the Journal of the American Heart Association aimed to find out if the ECG-derived marker of repolarization dispersion is associated with left ventricular diastolic dysfunction (LVDD) and functional class in pediatric patients with PAH.

“Biventricular diastolic dysfunction is an increasingly recognized comorbidity in PAH,” study authors wrote. “Recent studies suggest that electromechanical dyssynchrony and discoordination might be important contributors to the impaired myocardial relaxation in PAH.”

Repolarization dispersion is the interval between the peak and the end of the T wave (TpTe) and is determined by ECG. It has been independently linked to echocardiographic measures of diastolic dysfunction in past research.

In the current study, researchers investigated 3 main points:

  • Whether TpTe differs between the patients with PAH and healthy controls
  • Whether TpTe is associated with non‐invasive imaging-derived markers of LV diastolic discoordination
  • Whether combined measurements of repolarization dispersion and myocardial diastolic discoordination associate with PAH functional measurements

The study included 30 children with PAH and matched controls. Of the PAH group, 16 patients had idiopathic PAH, 10 had PAH associated with congenital heart disease, and 4 had hereditary familial PAH. All patients underwent standard 12-lead ECG scans to determine TpTe.

Echocardiography and myocardial strain analysis were also done on the same day to calculate diastolic relaxation fraction (DRF), which is a marker for diastolic electromechanical discoordination.

In the PAH group, 14 patients had LVDD based on echocardiographic criteria. Three patients in the PAH cohort were categorized as WHO functional class I, 12 were class II, 12 were class III, and 3 were class IV. All patients were being treated at the time of evaluation.

Patients with PAH had increased markers of LV diastolic discoordination compared with controls. Sub-analyses also compared controls with patients with and without echocardiographic signs of LVDD.

Patients with PAH and LVDD had significantly higher TpTe times versus the control group as well as patients with PAH and without LVDD. Patients with PAH and without LVDD, however, did not exhibit significantly different TpTe than controls. PAH patients with LVDD also had higher DRF compared with both the control group and those who had PAH without LVDD. But again, there was no significant difference between patients with PAH without LVDD and the control group when it came to DRF.

A 10-millisecond increase in TpTe was associated with a 0.023 increase in DRF after adjusting for body surface area, heart rate, right ventricular volumes, and function. Patients with PAH and LVDD also had higher heart rates than the other groups.

An analysis between controls, PAH patients with mildly reduce functional status (WHO class I or II), and moderate or severe functional status (class III and IV) found that the control group had decreased TpTe compared with those in the severe functional status group. Patients categorized as WHO class III or IV also had increased DRF compared with controls and with the mildly impaired functional status group.

Study authors noted limitations, such as the small study population and this being the first study to apply echocardiography-derived DRF, but concluded that the target markers are associated with worse LV diastolic function and WHO functional class in pediatric patients with PAH.

“In this study we found that TpTe was significantly elevated in children with PAH and was associated with the presence of LVDD. The observed relationship between TpTe and LV diastolic discoordination was significant independently of right ventricular performance markers,” the authors concluded. Future research is needed to assess TpTe and DRF as potential prognostic tools and investigate their association with PAH phenotypes.

Reference

Schäfer M, Frank BS, Ivy DD, et al. Repolarization dispersion is associated with diastolic electromechanical discoordination in children with pulmonary arterial hypertension. J Am Heart Assoc. Published online March 1, 2022. doi:10.1161/JAHA.121.024787

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