Yuki Nakamura, Michinari Hieda, Koshi Setoyama, Takeshi Someya, Nobuhito Nakanishi, Masashi Mitani, Taiki Makita, Keisuke Hidaka, Masahiro Takeo, Miyuki Nakahara, Hajime Miki, Yutaro Naka, Hiroki Okabe, Takeshi Onoue, Yasufumi Nagata, Mai Iwataki, Jun-Ichiro Koga, Yasushi Oginosawa, Masaharu Kataoka
Chronotropic incompetence was observed in 94% of patients with CTD-PAH. RV dysfunction was associated with worse chronotropic response and contributed to reduced exercise capacity.
BACKGROUND: Pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) is a progressive disease characterized by remodeling of the pulmonary vasculature, leading to increased right ventricular (RV) afterload and impaired exercise capacity.
RESEARCH QUESTION: The impact of RV dysfunction on chronotropic response remains poorly understood in patients with CTD-PAH.
STUDY DESIGN AND METHODS: This observational cohort study was conducted at our institution between April 2022 and March 2025. We enrolled 89 consecutive patients with CTD-PAH; 22 patients were excluded because of beta-blocker use (n = 9) or inability to exercise (n = 13). A total of 67 patients underwent echocardiography and exercise-stress right heart catheterization. Patients were classified into a preserved RV function group (tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure, ≥ 0.55; n = 47) and an impaired RV function group (tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure, < 0.55; n = 20); clinical parameters and outcomes were compared. Chronotropic incompetence was defined as peak heart rate (HR) < 85% of age-predicted HR and < 80% chronotropic response index: (maximum HR - resting HR)/(220 - age - resting HR).
RESULTS: Chronotropic incompetence affected 94% of patients. Age, sex, body size, BP, and left ventricular ejection fraction were comparable between the 2 groups. Compared with the preserved RV group, the impaired RV group had a lower chronotropic response index (preserved vs impaired RV group: 47.1% ± 20.3% vs 35.6% ± 14.8%; P = .034), lower delta HR/resting HR (0.56 ± 0.26 vs 0.36 ± 0.14; P = 0.003), lower mixed venous oxygen at rest (74.4% ± 3.7% vs 70.1% ± 7.0%; P = .004), lower peak oxygen consumption (517.1 ± 202.3 vs 402.2 ± 153.1 mL/min; P = .024), and higher peak pulmonary vascular resistance (2.2 ± 1.3 vs 3.5 ± 2.1 Wood units; P = .013).
INTERPRETATION: Chronotropic incompetence was observed in 94% of patients with CTD-PAH. RV dysfunction was associated with worse chronotropic response and contributed to reduced exercise capacity.