Could Heart Rate Variability Serve as a Prognostic Factor in Patients with Pulmonary Hypertension? A Single-center Pilot Study

OBJECTIVE
Heart rate variability (HRV), which is defined as cyclic changes in sinus rate with time, is used as a measure of cardiac autonomic tone. Our aim was to determine the impact of HRV on short-term prognosis in pulmonary hypertension (PH).


METHODS
We enrolled 64 PH patients and 69 healthy subjects (control group). Patients were evaluated by Holter-ECG, echocardiography, and laboratory tests. 24-h Holter-ECG monitoring was used for HRV. The development of adverse events (right heart failure, hospitalization, syncope, and death) during the 6-month follow-up was evaluated in PH group.


RESULTS
PH group (39 ± 16 years, 37.5% males) comprised of 16 patients with idiopathic pulmonary arterial hypertension (PAH) (25%), 36 patients with PAH associated with congenital heart disease (56.3%), 3 PAH associated with connective tissue disease (4.7%), 1 with portopulmonary (1.6%), and 8 chronic thromboembolic PH (12.5%). The time-dependent (standard deviation of all NN intervals for a selected time period [SDNN], standard deviation of the 5-min mean R–R intervals tabulated over an entire day [SDANN], SDNN Index, and Triangular Index) and frequency-dependent HRV indices (low frequency, high-frequency power, and total power,) were significantly reduced in those with PH. Functional class was negatively associated with SDNN, SDANN, SDNN Index, and Triangular Index. Adverse events developed in 25% of the patients during the 6-month follow-up period (200 ± 92 days) (7 patients had right-heart failure, 5 syncope, 12 patients were hospitalized, and 9 had died). All the time and frequency-dependent indices significantly associated with adverse events. Mortality correlated with SDNN (rS = −0.354, P = 0.005), SDANN (rS = −0.368, P = 0.004), SDNN Index (rS = −0.257, P = 0.045), Triangular Index (rS = −0.310, P = 0.014), and VLF (rS = −0.265, P = 0.039).


CONCLUSION
HRV is significantly depressed in patients with PH and is associated with the clinical status. HRV indices might predict clinical deterioration, adverse events, and mortality for 6 months. Non-invasive assessment of HRV through Holter-ECG may be a valuable and practical tool in risk stratification of patients with PH for short-term outcomes.