1. Effort Dependence of change in 6-Minute Walk Test in Pulmonary Hypertension was improved by Correction with the Change in Heart Rate: The Beat-Yield Pulmonology and Critical Care Department

2. Objective 6-Minute Walk Test (6MWT) is known to be affected by multiple factors. We hypothesize that heart rate would reflect the effort undertaken by patients during 6MWT and that effort dependent change can correct out the effort dependence of 6MWT.

3. Objective The importance of conducting this research is that 6MWT is the method that is most used to assess exercise tolerance in Pulmonary Hypertension (PH), to measure the response to therapy and to provide information on prognosis. By correlating the distance walked with dyspnea/fatigue index during exercise, a better assessment of the patient’s exercise capacity, cardiopulmonary effort and prognosis are provided.

4. Background Pulmonary Hypertension (PH) is a rare disease of increased pressure in the lungs arteries. There are 5 clinical classification of PH: 1. PAH includes idiopathic, familial and 2° to CTD, HIV, Drugs (illicit, diet), liver and thyroid diseases 2. PH with left heart disease (valve and/or chamber) 3. PH with lung diseases (COPD, ILD), hypoxemia (OSA) 4. PH due to chronic thrombotic and/or embolic disease 5. Miscellaneous such as Sarcoidosis, Histiocytosis X

5. PAH Pathophysiology: Arterial abnormalities such as inflammation, vasoconstriction, fibrosis, hypertrophy and cellular proliferation lead to increased pulmonary vascular resistance and ultimately, right heart failure. In severe PAH, patients may show symptoms of right ventricular (RV) failure: Progressive dyspnea, edema, abdominal bloating and decreasing functional ability. Overall median survival is 2.8 years without treatment

6. PAH

7. Hemodynamic criteria for diagnosing PAH Mean pulmonary artery pressure (mPAP) > 25 mmHg at rest and > 30 mm Hg with exertion (Normal 9- 19 mmHg) Pulmonary vascular resistance (PVR) > 3 Wood units (mmHg/L/min) (Normal 0.5-1.2 Wood units) Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg (Normal 4-12 mmHg)

8. PAH Screening test: Doppler Echo-Cardiography Diagnostic tests: 1. ECG (right heart changes) and C-XR (prominent pulmonary vessels) 2. Pulmonary Function test (airway and parenchymal lung disease) 3. Exercise and/or Overnight oximetry ± Polysomnography 4. V/Q scanning ± angiography 5. High resolution or spiral chest CT or MRI 6. Blood tests (serologies for collagen vascular disease, HIV infection, hypercoagulability, LFT, TSH and CBC)

9. PAH Confirmatory test: Right Heart Cath with vasodilator challenge 6MWT and functional status correlate with prognosis at the baseline and with treatment; also, help with treatment decision Reveal Score (risk score): 6-8 Low, 8-10 Moderate, >10 High

10. PAH Three principal pathways which are targeted for treatment: 1. Endothelin (Tracleer, Letaris, Opsumit) 2. Nitric Oxide (Adcirca, Revatio, Sildenafil, Adempas*) 3. Prostacyclin (Remodulin, Tyvaso, Ventavis, Flolan, Veletri, Epoprostenol) *FDA approved only for CTEPH

11. Methods Pulmonary hypertension (PH) patients, both male and female (N=30) were asked to undergo three consecutive 6MWTs (no exclusion criteria): The first, at the patient’s usual pace The second, one hour after at a slow pace The third (the last), one hour later at the patient’s fastest walking pace

12. Methods The factors studied were: Heart rate Dyspnea/Fatigue scores Peripheral Oxygen Saturations The distance walked The first three components were measured at rest and after the test each time.

13. Methods Beat-Yield (B Yield) was calculated from the 6MWT distance (meters=m)/change in Heart rate (ΔHR), (m/ΔHR).

14. Result Preliminary data shows B Yield and 6MW distance vary in linear fashion depending on exertion, with B Yield decreasing and 6MW distance increasing with increasing exertion (Fig. 1,2). 6MW distance in patient’s usual pace (Medium effort), is statistically equal to distance in slow pace (Low effort), 306 m v. 289 m, respectively (P =0.5220). Mean distance in fast pace (High effort), 367 m, is significantly more than mean distance in Medium effort, 306 m, or in Low effort, 289 m, (p=0.0028).

15. Fig. 1

16. Fig. 2

17. Result With regards to B yield (m/ΔHR), there is no difference between groups as a function of effort (18 v. 20 v. 26) and nearly linear with no statistically significant difference between different states (p=0.20). The B Yield is 10 times less susceptible to effort dependence, as the linear slope of B yield is −3.97 while that of the 6MW distance is 38.9 (p<0.05).

18. Conclusion The Effort dependence of 6MWT could negatively affect clinical trails and monitoring of patients, as their enthusiasm or mood would affect the outcome. The correction of 6MWT with the change in heart rate made the relationship less apparent _ no statistical difference in different effort beat yields. This may be a simple derived alternative measure to 6MWT and once validated, could be a useful variable in PH.