Journal of Cardiac and Pulmonary Rehabilitation
Open Access

Cardiopulmonary exercise testing; Pulmonary arterial; Hypertension

Introduction

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is associated with poor prognosis [1]. Many potential therapeutic options are now available for patients with PAH [2], including prostanoids [3] Endothelin receptor antagonists (ERA) [4] and phosphodiesterases type 5 inhibitors (PDE-5i) [5]. Current treatment algorithms [6] recommend an ERA or PDE-5i as a first line treatment for PAH of functional class II or III. Compared with monotherapy combination therapy improved exercise capacity and reduced the risk of clinical disease progression in patients with PAH [7]. However, the optimal strategy regarding the implementation of combination therapy has not yet been determined. Recognition of the potential value of cardiopulmonary exercise testing (CPX) in patients with PAH is increasing [8]. However, little is known about how exercise capacity changes over time under “goal oriented” sequential combination therapy in patients newly diagnosed with PAH. Goaloriented treatment of PAH patients according to results of CPX or 6-min walk distance. In that study, the treatment goals to stratify therapeutic decisions were set according to established prognostic criteria: 6-min walk distance, 380 m; peak oxygen uptake (VO2)>10.4 mL/min/kg; and peak systolic blood pressure during exercise, >120 mm Hg. These results compared favorably with a historical control group of PAH patients treated before 2002. However, these treatment goals might be suboptimal. For example, the most recent treatment guideline for PAH advocates that a peak VO2 cut-off value of ≥15 mL/ min/kg is a better indicator of prognosis [6]. We therefore observed the therapeutic effect of goal-oriented therapy evaluated by using CPX. The aim of this study was to use a peak VO2 cut-off of 15 mL/min/kg to guide combination therapy and observe exercise capacity over time by monitoring the results of CPX in patients with PAH.

Protocol

Treatment objectives were set and remedial choices were made by the laid out prognostic rule of a pinnacle VO2>15.0 mL/min/kg during CPX. Thirty patients recently determined to have PAH been treated with objective arranged consecutive blend treatment. Time was the first-line treatment, with PDE-5i as the favored mix accomplice. The patients went through CPX at pattern and Dіer 3, 6, and a year. We zeroed in on somewhat new files, in particular circulatory power (CP) and ventilator power (VP), in the CPX of PAH patients. CP was defined as the result of pinnacle O2 take-up and top systolic circulatory strain; VP was defined as pinnacle systolic pulse isolated continuously ventilation-CO2 creation slant.

Discussion

During the 12-month observation period, only one patient required intravenous epoprostenol Dіer 6 months). Ultimately, Dіer 12 months, ERA had been administered to 100% of the study patients and PDE-5i to 82%. Mean CP at baseline and Dіer 3, 6, and 12 months was 1807, 2063, 2248, and 2245 mm Hg•mL/min/kg, respectively, and mean VP was 2.93, 3.53, 4.16, and 3.68 mm Hg, respectively. CP was greater Dіer 6 months than at baseline (P=0.047); VP was greater Dіer 3 months than at baseline (P=0.019) and further improved at 6 months compared with 3 months (P=0.040). Our CPX-guided goal oriented treatment strategy might avoid excess medication and cost but still provide appropriate intervention by enabling treatment to be tailored to the individual patient therapy for at least 6 months. Future work is needed to determine the prognostic utility of them in patients with PAH.

One important finding of this study was that, to achieve the predefined treatment goals, combination treatment eventually became necessary in more than 80% of the patients, indicating that monotherapy lacks sufficient effectiveness in many patients with PAH. The strategy we followed was based on many factors, including the interval at which to monitor potential side effects of each medication, physician experience, practicability, and economic considerations. However, further studies are needed to define the variables most useful for clinical decision-making and the treatment principles that provide the best long-term results.

Conclusion

In patients with newly diagnosed PAH, sequential combination therapy significantly improved exercise capacity, particularly CP and VP. Sequential combination therapy may be a useful treatment option in patients with PAH. Therefore, repeated CPX assessment, including measurement of CP and VP can provide useful information regarding the effectiveness of goal-oriented treatment in patients with PAH.

Acknowledgement

None

Conflict of Interest

None

1. Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, et al. (2010) Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J 35: 1079-1087.

Indexed at, Google Scholar, Crossref

2. Fukumoto Y, Shimokawa H (2011) Recent progress in the management of pulmonary hypertension. Circ J 75: 1801-1810.

Indexed at, Google Scholar, Crossref

3. Okano Y, Yoshioka T, Shimouchi A, Satoh T, Kunieda T (1997) Orally active prostacyclin analogue in primary pulmonary hypertension. Lancet 349: 1365.

Indexed at, Google Scholar, Crossref

4. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, et al. (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346: 896-903.

Indexed at, Google Scholar, Crossref

5. Humbert M, Sitbon O, Simonneau G (2004) Treatment of pulmonary arterial hypertension. N Engl J Med 351: 1425-1436.

Indexed at, Google Scholar, Crossref

6. Hoeper MM, Markevych I, Spiekerkoetter E, Welte T, Niedermeyer J (2005) Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J 26: 858-863.

Indexed at, Google Scholar, Crossref

7. Arena R, Lavie CJ, Milani RV, Myers J, Guazzi M (2010) Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review. J Heart Lung Transplant 29: 159-173.

Indexed at, Google Scholar, Crossref

8. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, et al. (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115: 343-349.

Indexed at, Google Scholar, Crossref