Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing

doi:10.1016/S1053-2498(03)00064-0

The Journal of Heart and Lung Transplantation

Volume 23, Issue 1, January 2004, Pages 88-95

https://doi.org/10.1016/S1053-2498(03)00064-0 Get rights and content

Abstract

Background

Given the recent development of newer and less-invasive treatments for pulmonary hypertension, and the long wait for lung transplantation, early and correct diagnosis of this condition is increasingly important. The purpose of this study was to determine and improve the accuracy of a non-invasive, cardiopulmonary exercise-testing algorithm for detecting a pulmonary vascular limit to exercise.

Methods

We performed 130 consecutive, incremental cycling-exercise tests for exertional symptoms with pulmonary and radial artery catheters in place. Pulmonary vascular limit was defined as pulmonary vascular resistance at maximum exercise >120 dynes · sec/cm⁵ and a peak-exercise systemic oxygen delivery <80% predicted, without a pulmonary mechanical limit or poor effort. We applied a previously reported non-invasive exercise-test-interpretation algorithm to each patient and sequentially manipulated branch point threshold values to maximize accuracy.

Results

The sensitivity of the original non-invasive algorithm for pulmonary vascular limit was 79%, specificity was 75%, and accuracy was 76%. Sensitivity did not change with systematic alteration of branch-point threshold values, but specificity and accuracy improved to 88% and 85%, respectively. Accuracy improved most by modifying the threshold values for percent predicted maximum oxygen uptake and carbon dioxide output ventilatory equivalents at lactate threshold.

Conclusion

Non-invasive cardiopulmonary exercise testing is a useful tool for detecting and excluding a pulmonary vascular limit and for determining whether abnormal pulmonary hemodynamics limit aerobic capacity.

Section snippets

Study design

We evaluated 130 consecutive, clinically indicated cardiopulmonary exercise tests that were performed with radial and pulmonary artery (PA) catheters in place at the Massachusetts General Hospital Cardiopulmonary Exercise Laboratory. We applied a widely used, non-invasive cardiopulmonary exercise test diagnostic algorithm27 to each test and sequentially altered branch-point threshold values to maximize accuracy in diagnosing PVL.

Patient population

Sixty patients were women. Ages ranged between 21 and 79 years,

Pulmonary function and exercise test results

For the 130 patients, the forced expiratory volume in 1 second was 2.3 ± 0.08 liters (SEM), which was 81% ± 2.0% predicted. The maximum work attained was 80 ± 5.0 W. The V̇o₂max was 1,104 ± 43.8 ml/min, which was 54% ± 1.3% predicted.

Traditional indices of PVL

The sensitivity of the isolated peak exercise Vd/Vt for PVL was 20%, with specificity of 85% and accuracy of 56%. Similarly, the isolated peak exercise PA-a_O2 had a sensitivity for PVL of 24%, specificity of 92%, and accuracy of 60%.

Non-invasive exercise algorithm-derived diagnoses

We excluded from the study 33

Discussion

A major pitfall in the diagnosis of PVL is the relative insensitivity of the clinical evaluation and of physiologic measurements made at rest. Even under the stress of exercise, isolated surrogate markers of PVL, such as Vd/Vt and PA-a_O2, may be normal when pulmonary hypertension is present.19, 25 Consequently, a new strategy for diagnosing PVL (and other disease states that limit exercise) has evolved, which is based on patterns of change in a few key physiologic responses to incremental

Conclusion

Cardiopulmonary exercise testing is a useful tool in detecting pulmonary vascular disease and its effects on overall aerobic capacity. After minor modification, a non-invasive diagnostic strategy based on the pattern of physiologic responses to incremental exercise can accurately identify and exclude abnormal pulmonary hemodynamics as a cause of exertional intolerance.

Acknowledgements

The authors thank Barnard Hoop, PhD, and Paul Pappagianopolous, MS, for their technical assistance.

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Noninvasive cardiopulmonary exercise testing (CPET) is a useful screening test for pulmonary hypertension that can quantify the degree of exercise impairment and rule out a limit due to pulmonary parenchymal disease. Invasive CPET, with the addition of both a radial artery catheter and a pulmonary artery catheter, allows for the direct calculation of the Fick cardiac output, sampling of venous and arterial blood gases, and measurements of right and left sided pressures during exercise. Invasive CPET can add specificity to the noninvasive test and distinguish between pulmonary arterial and venous hypertension not apparent during the resting right heart catheterization. In this article, we provide an overview of both noninvasive and invasive CPET, a description of various exercise variables obtained during CPET, and analysis of their use in diagnosing disorders of pulmonary circulation.
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Citation Excerpt :
At the end of the follow-up period, however, all but 6 patients were receiving PAH-specific therapy. Maximal and submaximal CPET responses were typical of PAH19,30,33–35: (i) reduced peak work rate, Vo2, HR, oxygen pulse, and Spo2 coupled with markedly increased ΔVE/ΔVco2; (ii) decreased Vo2 and PetCO2 at the VAT; and (iii) steeper ΔHR/ΔVo2 (Table II; Figure 1, upper panels for ΔHR/ΔVo2 in representative subjects). Dyspnea ratings and dyspnea–leg effort differences were significantly higher in patients than controls (Table II).
Delayed postexercise heart rate recovery (HRR) has been associated with disability and poor prognosis in chronic cardiopulmonary diseases. The usefulness of HRR to predict exercise impairment and mortality in patients with pulmonary arterial hypertension (PAH), however, remains largely unexplored.
Seventy-two patients with PAH of varied etiology (New York Heart Association classes I-IV) and 21 age- and gender-matched controls underwent a maximal incremental cardiopulmonary exercise test (CPET), with heart rate being recorded up to the fifth minute of recovery.
Heart rate recovery was consistently lower in the patients compared with the controls (P < .05). The best cutoff for HRR in 1 minute (HRR_1min) to discriminate the patients from the controls was 18 beats. Compared with patients with HRR_1min ≤18 (n = 40), those with HRR_1min >18 (n = 32) had better New York Heart Association scores, resting hemodynamics and 6-minute walking distance. In fact, HRR_1min >18 was associated with a range of maximal and submaximal CPET variables indicative of less severe exercise impairment (P < .05). The single independent predictor of HRR_1min ≤18 was the 6-minute walking distance (odds ratio [95% CI] 0.99 [0.98-1.00], P < .05). On a multiple regression analysis that considered only CPET-independent variables, HRR_1min ≤18 was the single predictor of mortality (hazard ratio [95% CI] 1.19 [1.03-1.37], P < .05).
Preserved HRR_1min (>18 beats) is associated with less impaired responses to incremental exercise in patients with PAH. Conversely, a delayed HRR_1min response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated (and costlier) analyses provided by a full CPET are not available.
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Lung transplant waiting list mortality makes it necessary to prioritize the criteria.
To analyze the role of the six-minute walking test (6MWT) as a predictor of waiting list mortality.
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View all citing articles on Scopus

^☆: This study was supported by National Institutes of Health Grant 1K24 HLO4022-01 and by AHA Grant-in-aid 96-50406.

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Advanced lung disease—medical aspectsDiagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing☆

Abstract

Background

Methods

Results

Conclusion

Section snippets

Study design

Patient population

Pulmonary function and exercise test results

Traditional indices of PVL

Non-invasive exercise algorithm-derived diagnoses

Discussion

Conclusion

Acknowledgements

J Am Coll Cardiol

Lancet

Clin Chest Med

Clin Chest Med

Chest

Clin Chest Med

Am J Med

Am J Med

Chest

Clin Chest Med

Chest

Chest

Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patents with pulmonary arterial hypertensiona double-blind, randomized, placebo-controlled trial

Am J Resp Crit Care Med

Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension

Am J Resp Crit Care Med

Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue

N Engl J Med

Long-term use of inhaled nitric oxide for pulmonary hypertension

Respir Care

Appetite-suppressant drugs and the risk of primary pulmonary hypertension

N Engl J Med

Primary pulmonary hypertension and fenfluramine use

Br Heart J

Primary pulmonary hypertension; a national prospective study

Ann Intern Med

Primary pulmonary hypertensionnatural history and the importance of thrombosis

Circulation

Advanced lung disease—medical aspects
Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing☆