A Look at the Use of Echocardiography to Assess Macitentan Effects, Predict Mortality in PAH

December 5, 2020
Jaime Rosenberg

Two studies presented at CHEST 2020 assessed the impact of macitentan on cardiac function in pulmonary arterial hypertension (PAH) and determined what role reproducible exercise echocardiographic parameters have in predicting survival.

Two study abstracts presented at the CHEST 2020 annual meeting explored the use of echocardiography in pulmonary arterial hypertension (PAH), with 1 study assessing the impact of macitentan on cardiac function in PAH as measured by echocardiography and the other determining what role reproducible exercise echocardiographic parameters have in predicting survival of the condition.

In the first abstract,1 researchers assessed a subgroup of 46 treatment-naïve patients with PAH enrolled in the 52-week, multicenter, open-label, single-arm phase 4 REPAIR study. Among these patients who were treated with macitentan, the researchers observed notable improvements in right ventricular (RV) function as determined by echocardiography.

By week 26, key RV variables measured by echocardiography showed:

  • A mean change of -2.8 mm (range, -4.7 to -0.8; P = .0071 for RV end diastolic dimension [RVEDD])
  • A mean change of 7.5% (range, 4.4%-10.7%; P < .0001 for RV fractional area change [FAC])
  • A mean change of 11.6 mL (range, 3.2-20.0; P = .0089 for RV stroke volume [RVSV])
  • A mean change of 0.5 L/min (range, -0.1 to 1.1; P = .1152 for RV cardiac output)
  • A mean change of 2.5 mm (range, 1.4-3.6; P < .0001 for tricuspid annular plane systolic excursion [TAPSE])
  • A mean change of 0.19 (range, 0.06-0.32; P = .0065 for the mitral E/A ratio)
  • A mean change of -3.0% (range, -4.7% to -1.4%; P = .0006 for the 2D global longitudinal RV strain)
  • A mean change of -7 bpm (range, -10 to -4; P < .0001 for heart rate)

According to the researchers, for parameters that saw significant improvements by week 26, findings were maintained at week 52.

“In the REPAIR echo substudy, macitentan treatment was associated with significant improvements in RV function measured by echo at week 26 and 52, including RVEDD, RVSV, TAPSE, and RV strain, key prognostic markers in PAH,” wrote the researchers, reflecting on the findings. “Normalization of the mitral flow (E/A ratio) suggests that these improvements in RV function are also associated with improved left ventricle diastolic function.”

The second abstract2 compiled data on 45 patients with PAH to determine the role of RV exercise stress echocardiography, a less established method than transthoracic echocardiography, in risk assessment of PAH.

Each patient received an echocardiography of their RV parameters in the apical 4-chamber view at rest and during exercise using a bicycle ergometer. Results showed that TAPSE and RV FAC during exercise had strong associations with subsequent PAH mortality. Mortality also trended with RV sphericity index, although it was not statistically significant.

“Reproducible exercise echocardiographic parameters may have a role in clinical management of PAH,” wrote the researchers. “Use of these parameters can also aid PAH study design through better identification of PAH subjects at increased risk of clinical deterioration and mortality.”

Notably, a decline in TAPSE during exercise was strongly associated with mortality, with researchers observing trends for decreasing FAC and increasing exercise RV sphericity during the exercise.

References

1. Torbicki A, Channick R, Cottreel E, et al. Effects of macitentan on cardiac function in pulmonary arterial hypertension: results from the REPAIR echocardiography substudy. Presented at: CHEST 2020; October 18-21, 2020. Abstract 2227A. doi:10.1016/j.chest.2020.08.1899

2. El-Yafawi R, Cohen A, Wirth J. Does right ventricle exercise stress echocardiography predict survival in PAH? Presented at: CHEST 2020; October 18-21, 2020. Abstract 2161A. doi:10.1016/j.chest.2020.08.1859