Relationship Between Right Ventricular Function and Chronotropic Incompetence in Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

Figures

• 

  Figure 1. Study design. Patients with pulmonary arterial hypertension associated with connective tissue disease underwent exercise right heart catheterization (N = 89). Beta-blocker usage (n = 9) and exercise intolerance (n = 13) were excluded. The remaining 67 patients were divided into 2 groups by right ventricular function: TAPSE/sPAP ≥ 0.55 or < 0.55. sPAP = systolic pulmonary arterial pressure; TAPSE = tricuspid annular plane systolic excursion.

• 

  Figure 2. A-C, Prevalence of chronotropic incompetence. A, Chronotropic incompetence was observed in 94% (63/67) of patients with pulmonary arterial hypertension undergoing exercise right heart catheterization. B, The TAPSE/sPAP ≥ 0.55 group had a 91.5% chronotropic incompetence prevalence, and the TAPSE/sPAP < 0.55 group had a 100% prevalence (P = .086). C, Peak HR > 100 beats/min was observed in 68.0% of patients in the TAPSE/sPAP ≥ 0.55 vs 65.0% of patients in the TAPSE/sPAP < 0.55 group (P = .806). Chronotropic incompetence was defined as < 85% of age-predicted HR: (220 − age) beats/min, and < 80% of the chronotropic response index: (peak HR − resting HR)/(220 − age − resting HR) × 100. HR = heart rate; sPAP = systolic pulmonary arterial pressure; TAPSE = tricuspid annular plane systolic excursion.

• 

  Figure 3. A, B, CRI and delta HR/resting HR. The relationship between TAPSE/sPAP and chronotropic response in patients with pulmonary arterial hypertension associated with connective tissue disease. The chronotropic response, evaluated using the CRI and delta HR/resting HR, was significantly lower in the TAPSE/sPAP < 0.55 group. CRI = chronotropic response index; HR = heart rate; sPAP = systolic pulmonary arterial pressure; TAPSE = tricuspid annular plane systolic excursion.

• 

  Figure 4. A, B, Pulmonary vascular resistance and peak V˙o2. The relationship between TAPSE/sPAP and exercise intolerance in patients with pulmonary arterial hypertension associated with connective tissue disease. The TAPSE/sPAP < 0.55 group had higher PVR and lower V˙o2 at peak. PVR = pulmonary vascular resistance; sPAP = systolic pulmonary arterial pressure; TAPSE = tricuspid annular plane systolic excursion; V˙o2 = maximum oxygen consumption.

• 

  Figure 5. Pathophysiological cascade linking RV dysfunction to chronotropic incompetence and exercise intolerance in patients with pulmonary arterial hypertension associated with connective tissue disease. The sequence begins with patients with connective tissue disease who have pulmonary arterial hypertension characterized by elevated PVR and impaired RV function (TAPSE/sPAP < 0.55). This leads to decreased RV-SV and Svo2, which reduces left ventricular preload and subsequently decreases CO. The diminished CO results in lower sBP and reduced peak V˙o2 during exercise. These hemodynamic abnormalities contribute to worsening chronotropic incompetence, manifested by reduced CRI and decreased delta HR relative to resting HR. This chronotropic dysfunction ultimately results in severe exercise intolerance. The gray box outlines the underlying physiological mechanisms: decreased sBP during exercise leads to reduced baroreflex sensitivity, which causes decreased sympathetic nervous system activity. This autonomic dysregulation disturbs the normal HR increase during exercise, creating a vicious cycle that perpetuates exercise intolerance. CO = cardiac output; CRI = chronotropic response index; HR…