A Noninvasive Assessment of Pulmonary Perfusion Abnormality in Patients With Primary Pulmonary Hypertension

doi:10.1378/chest.119.3.824

CHEST

Volume 119, Issue 3, March 2001, Pages 824-832

https://doi.org/10.1378/chest.119.3.824 Get rights and content

Study objectives:

The ventilatory equivalent for CO₂ (ie, the ratio of minute ventilation[Ve] to carbon dioxide output[Vco₂]) is increased in patients with primary pulmonary hypertension (PPH) consequent to an increase inphysiologic dead space and alveolar ventilation. We wished to seewhether the Ve/Vco₂ratio correlated with the abnormality in pulmonary hemodynamics in PPHpatients and whether it changed in response to prostacyclininfusion.

Methods:

Following right-sided heartcatheterization, 10 patients with severe PPH were studied in thecoronary-care unit while hemodynamic and gas exchange measurements weremeasured simultaneously before and after infusion with epoprostenol(Epo), a prostacyclin analog. Studies were performed at baseline and during IV infusion of two to three increasing dosages of Epo in 10 PPHpatients (NYHA class III-IV). Four patients had radial artery cathetersfor simultaneous blood gas measurements. Nine healthy subjects who werematched by sex, height, and weight underwent gas exchange analysesonly.

Results:

The mean (± SD)Ve/Vco₂ ratio washigher in PPH patients than in control subjects (50.7 ± 9.7 vs30.6 ± 3.8; p < 0.001). Thirteen measurements made in fourpatients showed that the Ve/Vco₂ ratiocorrelated with the physiologic dead space/tidal volume ratio(r = 0.78; p = 0.002). The Ve/Vco₂ ratiomeasurement at baseline correlated significantly with total pulmonaryvascular resistance (TPVR) (r = 0.70; p = 0.02) butnot with mean pulmonary artery pressure (mPAP) or cardiac index. DuringEpo infusion, the Ve/Vco₂ ratio decreasedwith increasing dosage in 6 of 10 patients, with no change or slightincreases in the 4 remaining patients. Considering all doses, the Ve/Vco₂ ratio decreasedsignificantly in response to the short-term administration of Epo. Thedecrease tended to parallel the pattern of decrease in TPVR, but thechanges in both variables were too small to provide a statisticallysignificant correlation. The mPAP did not change significantly inresponse to Epo infusion, although TPVR did change at the highestdosage.

Conclusions:

In patients with severe PPH, the Ve/Vco₂ ratiocorrelated significantly with TPVR but not with mPAP or cardiac index. The Ve/Vco₂ ratiodecreased systematically from baseline with the dose of Epo in some butnot all patients. The Ve/Vco₂ ratio and TPVRdecreased significantly in response to Epo when all doses wereconsidered. Further studies are needed to elucidate whether noninvasivegas exchange measurements may be clinically useful in the evaluation of the severity of pulmonary vascular disease and the effectiveness of pulmonary vasodilator therapy.

Section snippets

Patients

This study was approved by our institutional review board onresearch on human subjects. After giving informed consent, 10 patientswith PPH and 9 healthy subjects who were matched for age, size, and gender were entered into the study. Patients with primary heart diseaseor secondary pulmonary hypertension were excluded. We used the criteriafor the diagnosis of PPH from the Registry on Primary PulmonaryHypertension of the National Institutes of Health.¹⁰ Allpatients were in New York Heart

Subject Demographics

There were no significant differences in age, sex, height, orweight between PPH patients and healthy subjects (Table 1). Four of our 10 patients did not have TR, and 3 patients (patients 5,6, and 8) had PFOs with right-to-left shunts defined byechocardiography. Of the seven patients with measured carbon monoxidediffusing capacity, all were below predicted values, but only one had avalue < 80% of that predicted.

Cardiovascular Responses to Epo Infusion

All patients received continuous IV infusion of Epo at two dosagelevels, and three

Discussion

The steady-state ventilatory equivalent for CO₂ (ie, the Ve/Vco₂ratio) reflects the ventilatory efficiency of gas exchange. The stablegas exchange ratio (RER) shown in Table 2 indicates that patients werein a gas exchange steady state during their studies. A higher Ve/Vco₂ratio describes a greater ventilatory requirement for eliminating the CO₂ produced by aerobic metabolism and defines areduced ventilatory efficiency. The reduced ventilatory efficiency iscaused by an increase in physiologic

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Cited by (49)

Pulmonary hypertension and ventilation during exercise: Role of the pre-capillary component
2017, Journal of Heart and Lung Transplantation
Citation Excerpt :
Patients with CpcPH presented with modestly but significantly lower Sao2 at rest, possibly secondary to low mixed venous oxygen content36,37 and eventually suggesting chronic chemoreflex stimulation; however, hypoxemia is generally unrelated to increased Ve/VCO2 slope in patients with pulmonary vascular disease.29,36 Finally, ventilation/perfusion matching30,36,37 is less likely to explain exercise hyperpnea in our study. Ventilation/perfusion inequality may be effectively present in patients with PAH,30 but it is thought to be generally mild,36,37 which contrasts with patients with LHD, where high dead space ventilation may significantly account for exercise-induced hyperventilation.31
Excessive exercise-induced hyperventilation and high prevalence of exercise oscillatory breathing (EOB) are present in patients with post-capillary pulmonary hypertension (PH) complicating left heart disease (LHD). Patients with pre-capillary PH have even higher hyperventilation but no EOB. We sought to determine the impact of a pre-capillary component of PH on ventilatory response to exercise in patients with PH and left heart disease.
We retrospectively compared patients with idiopathic or heritable pulmonary arterial hypertension (PAH, n = 29), isolated post-capillary PH (IpcPH, n = 29), and combined post- and pre-capillary PH (CpcPH, n = 12). Diastolic pressure gradient (DPG = diastolic pulmonary artery pressure − pulmonary wedge pressure) was used to distinguish IpcPH (DPG <7 mm Hg) from CpcPH (DPG ≥7 mm Hg).
Pulmonary vascular resistance (PVR) was higher in PAH, intermediate in CpcPH, and low in IpcPH. All patients with CpcPH but 1 had PVR >3 Wood unit. Exercise-induced hyperventilation (high minute ventilation over carbon dioxide production, low end-tidal carbon dioxide) was marked in PAH, intermediate in CpcPH, and low in IpcPH (p < 0.001) and correlated with DPG and PVR. Prevalence of EOB decreased from IpcPH to CpcPH to PAH (p < 0.001).
Patients with CpcPH may have worse hemodynamics than patients with IpcPH and distinct alterations of ventilatory control, consistent with more exercise-induced hyperventilation and less EOB. This might be explained at least in part by the presence and extent of pulmonary vascular disease.
The strengths and weaknesses of non-invasive parameters obtained by echocardiography and cardiopulmonary exercise testing in comparison with the hemodynamic assessment by the right heart catheterization in patients with pulmonary hypertension
2017, Advances in Medical Sciences
Pulmonary hypertension (PH) diagnosis requires invasive assessment by right heart catheterization (RHC), but screening and monitoring are performed using non-invasive methods: echocardiography and cardiopulmonary exercise testing (CPET). The aim of the study was to assess correlations between the parameters obtained in non-invasive testing and RHC in patients with PH of different etiologies.
The study included 53 medical records of PH patients (32 women) aged 29–81 years. We analyzed correlations between RHC (systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP), pulmonary vascular resistance (PVR), cardiac output (CO)) and echocardiographic (tricuspid annular plane systolic excursion (TAPSE), sPAP) and CPET parameters (end-tidal oxygen and carbon dioxide pressures (PetO₂, PetCO₂), ventilation efficiency (VE/VCO₂) slope).
Echocardiographic estimation correlated well with RHC measurement of sPAP (r = 0.65, P < 0.001). TAPSE correlated with PVR assessed with thermodilution method (r = −0.5, P = 0.005), dPAP (r = −0.53, P = 0.002) and CO (r = 0.53, P = 0.002). PVR assessed with thermodilution and Fick methods showed positive correlation with PetO₂ (r = 0.74, P < 0.001 and r = 0.72, P < 0.001) and negative correlation with PetCO₂ (r = −0.59, P = 0.004 and r = −0.64, P = 0.002) at the anaerobic threshold. VE/VCO₂ slope correlated with dPAP (r = 0.43, P = 0.04) and PVR calculated with both methods (r = 0.52, P = 0.01 and r = 0.52, P = 0.02).
Simple cardiac function indicators obtained by commonly used non-invasive methods allow only approximate estimation of the main hemodynamic RHC-derived parameters: sPAP, CO and PVR. Obtained results suggest the relationship between RV dysfunction and ventilation abnormalities in PH patients.
Submaximal Exercise Pulmonary Gas Exchange in Left Heart Disease Patients with Different Forms of Pulmonary Hypertension
2015, Journal of Cardiac Failure
We determined whether pulmonary gas exchange indices during submaximal exercise are different in heart failure (HF) patients with combined post- and pre-capillary pulmonary hypertension (PPC-PH) versus HF patients with isolated post-capillary PH (IPC-PH) or no PH.
Pulmonary hemodynamics and pulmonary gas exchange were assessed during rest and submaximal exercise in 39 HF patients undergoing right heart catheterization. After hemodynamic evaluation, patients were classified as having no PH (n = 11), IPC-PH (n = 12), or PPC-PH (n = 16). At an equivalent oxygen consumption, end-tidal CO₂ (PETCO₂) and arterial oxygen saturation (SaO₂) were greater in no-PH and IPC-PH versus PPC-PH patients (36.1 ± 3.2 vs 31.7 ± 4.5 vs 26.2 ± 4.7 mm Hg and 97 ± 2 vs 96 ± 3 vs 91 ± 1%, respectively). Conversely, dead-space ventilation (V_D/V_T) and the ventilatory equivalent for carbon dioxide $({\dot{V}}_{E} / \dot{V} {CO}_{2} ratio)$ were lower in no-PH and IPC-PH versus PPC-PH patients (0.37 ± 0.05 vs 0.38 ± 0.04 vs 0.47 ± 0.03 and 38 ± 5 vs 42 ± 8 vs 51 ± 8, respectively). The exercise-induced change in V_D/V_T, ${\dot{V}}_{E} / \dot{V} {CO}_{2}$ ratio, and PETCO₂ correlated significantly with the change in mean pulmonary arterial pressure, diastolic pressure difference, and transpulmonary pressure gradient in PPC-PH patients only.
Noninvasive pulmonary gas exchange indices during submaximal exercise are different in HF patients with combined post- and pre-capillary PH compared with patients with isolated post-capillary PH or no PH.
The lowest VE/VCO<inf>2</inf> ratio best identifies chronic thromboembolic pulmonary hypertension
2014, Thrombosis Research
Citation Excerpt :
Because of the reasons mentioned above, VE/VCO2 ratio is more reliable than the VE/VCO2 slope. The roles of VE/VCO2 ratio at rest, or at AT have been explored in some studies about PH [14–19]. Results showed that VE/VCO2 at rest and VE/VCO2 at AT were significantly higher in idiopathic PH than in healthy controls.
The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH.
15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET.
The lowest VE/VCO₂ was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p < 0.005). The VE/VCO₂ slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p < 0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2 L/min, p < 0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO₂ ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p < 0.001). The lowest VE/VCO₂ was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p < 0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients.
CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.
The usefulness of submaximal exercise gas exchange to define pulmonary arterial hypertension
2011, Journal of Heart and Lung Transplantation
The 6-minute walk test is widely used to characterize activity tolerance and response to therapy in pulmonary arterial hypertension (PAH) but provides little information about cardiopulmonary pathophysiology. The aim of the present study was to determine whether measures of pulmonary gas exchange during relatively light exercise could differentiate between PAH patients and healthy individuals and also stratify disease severity.
The study comprised 40 PAH patients and 25 matched controls. Each completed a sub-maximal exercise test, consisting of 2 minutes of rest, 3 minutes of exercise, and 1 minute of recovery. Ventilation, pulmonary gas exchange, arterial oxygen saturation (Sao₂), and heart rate were measured throughout using a simplified gas analysis system.
A number of gas exchange variables differentiated PAH patients and controls. End-tidal CO₂ (P_ETco₂) and Sao₂ were lower in PAH vs controls (31 ± 7 vs 39 ± 3 mm Hg and 89% ± 5% vs 95% ± 2%, respectively, p < 0.05). Breathing efficiency (V_E/Vco₂ ratio) was poorer in PAH vs controls (42 ± 10 vs 33 ± 5, p < 0.05). In addition, P_ETco₂ and V_E/Vco₂ discriminated between different severities of PAH.
Gas exchange variables obtained during light sub-maximal exercise differentiated PAH patients from healthy controls and also between different severities of PAH. Sub-maximal exercise gas exchange may be a useful end point measure in a PAH population.
Hypoventilation syndromes
2010, Clinics in Chest Medicine
Citation Excerpt :
Any respiratory system disorder that increases the absolute value of dead space or elevates Vd/Vt by reducing tidal volume may potentially lead to hypoventilation. The former category of diseases consist mainly of those that attenuate the pulmonary vasculature, such as primary pulmonary hypertension, chronic pulmonary thromboembolic disease, and pulmonary hypertension secondary to collagen-vascular diseases199; interstitial lung diseases such as usual interstitial pneumonia200–202; and causes of secondary pulmonary hypertension such as human immunodeficiency virus infection or end-stage liver disease with portal hypertension. Pulmonary parenchymal diseases that reduce tidal volume due to restrictive ventilatory impairment include interstitial lung disorders such as sarcoidosis, interstitial disease (either primary or associated with collagen-vascular disorders), or cystic fibrosis.200–202

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: Supported in part by the Milly Liang Liu, MD, and Steve CK Liu, MD, Research Fund and by Glaxo Wellcome.

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CHEST

Clinical InvestigationsA Noninvasive Assessment of Pulmonary Perfusion Abnormality in Patients With Primary Pulmonary Hypertension

Study objectives:

Methods:

Results:

Conclusions:

Section snippets

Patients

Subject Demographics

Cardiovascular Responses to Epo Infusion

Discussion

Am J Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Ann Thorac Surg

Current concepts: primary pulmonary hypertension

N Engl J Med

Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure

Circulation

Clinical Investigations
A Noninvasive Assessment of Pulmonary Perfusion Abnormality in Patients With Primary Pulmonary Hypertension