The Right Ventricular-Pulmonary Arterial Coupling and Diastolic Function Response to Therapy in Pulmonary Arterial Hypertension

Rebecca R. Vanderpool, Kendall S. Hunter, Michael Insel, Joe G.N. Garcia, Edward J. Bedrick, Ryan J. Tedford, Franz P. Rischard

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Multiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect because most patients remain at intermediate or high risk after initial treatment, with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy. Research Question: Does RV adaptation predict therapeutic response over time? Study Design and Methods: We evaluated 52 incident treatment-naive patients with advanced PAH by catheterization and cardiac imaging longitudinally at baseline, follow-up 1 (∼3 months), and follow-up 2 (∼18 months). All patients received goal-directed therapy with parenteral treprostinil and/or combination therapy with treatment escalation if functional class I or II was not achieved. On the basis of their therapeutic response, patients were evaluated at follow-up 1 as nonresponders (died) or as responders, and again at follow-up 2 as super-responders (low risk) or partial responders (high/intermediate risk). Multiparametric risk was based on a simplified European Respiratory Society/European Society of Cardiology guideline score. RV adaptation was evaluated with the single-beat coupling ratio (Ees/Ea) and diastolic function with diastolic elastance (Eed). Data are expressed as mean ± SD or as OR (95% CI). Results: Nine patients (17%) were nonresponders. PAH-directed therapy improved the European Respiratory Society low-risk score from 1 (2%) at baseline to 23 (55%) at follow-up 2. Ees/Ea at presentation was nonsignificantly higher in responders (0.9 ± 0.4) vs nonresponders (0.6 ± 0.4; P = .09) but could not be used to predict super-responder status at follow-up 2 (OR, 1.40 [95% CI, 0.28-7.0]; P = .84). Baseline RV ejection fraction and change in Eed were successfully used to predict super-responder status at follow-up 2 (OR, 1.15 [95% CI, 1.0-1.27]; P = .009 and OR, 0.29 [95% CI, 0.86-0.96]; P = .04, respectively). Interpretation: In patients with advanced PAH, RV-pulmonary arterial coupling could not discriminate irreversible RV failure (nonresponders) at presentation but showed a late trend to improvement by follow-up 2. Early change in Eed and baseline RV ejection fraction were the best predictors of therapeutic response.

Original languageEnglish (US)
Pages (from-to)1048-1059
Number of pages12
JournalCHEST
Volume161
Issue number4
DOIs
StatePublished - Apr 2022
Externally publishedYes

Keywords

  • hemodynamics
  • pulmonary hypertension
  • right ventricular function
  • treatment effect
  • ventricular/vascular coupling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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