0
Editorials |

From the Echo Bed to the Pulmonary Vascular BedDobutamine Echo in Pulmonary Hypertension: Dobutamine Testing in the Noninvasive Laboratory FREE TO VIEW

Lawrence G. Rudski, MD; Eduardo Bossone, MD, PhD, FCCP; David Langleben, MD
Author and Funding Information

From the Division of Cardiology, Jewish General Hospital, McGill University; and Department of Cardiology and Cardiac Surgery, University Hospital Scuola Medica Salernitana.

CORRESPONDENCE TO: Lawrence G. Rudski, MD, Center for Pulmonary Vascular Diseases, Division of Cardiology, Jewish General Hospital, McGill University, 3755 Cote Sainte Catherine Rd, Ste E-206, Montreal, QC, H3T 1E2, Canada; e-mail: lrudski@jgh.mcgill.ca


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following conflicts of interest: Dr Rudski has minor stock holdings in General Electric outside of a managed portfolio. Drs Bossone and Langleben have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):876-878. doi:10.1378/chest.14-0856
Text Size: A A A
Published online

Cardiovascular physiology, in its simplest form, can be summed up by two very basic equations: right = left and V = IR (where V indicates voltage, and IR indicates the product of current and resistance). The former equation states that, in the absence of shunt, the left heart can only pump what it receives from the right. The latter equation, Ohm’s law, is transposed in cardiology as pressure = flow × resistance. In vivo, of course, this relationship is far more complex as the pulmonary circulation is not a set of rigid pipes, and the flow is pulsatile. The mechanism of right ventricle (RV) contraction remains enigmatic, and fully characterizing the RV-pulmonary artery coupling relationship is difficult.1 The challenge to clinicians and scientists is to move beyond these very basic equations, while respecting their principles.

Pulmonary arterial hypertension (PAH) is a devastating condition that dramatically reduces longevity and impairs quality of life.2 Prognosis ultimately is determined by the ability of the RV to adapt and compensate for the increased afterload. Adding to the misfortune of the disease is the delay in its diagnosis, with a median delay of > 2 years from onset of symptoms—a time frame that has not changed since the 1970s.3 In recent years, clinicians have been sensitized to use noninvasive tests, particularly echocardiography, to screen symptomatic patients as well as asymptomatic patients in certain high-risk groups, such as those with connective tissue disorders or a family history of PAH. Although resting echocardiography can be used as an effective screening tool, the literature has been mixed when reporting its accuracy if one relies solely on echo-derived systolic pulmonary arterial pressure (sPAP).4,5 The reference standard, right-sided heart catheterization, would obviously be impractical as a screening tool given its cost, risk, and availability.

Until its end stages, PAH in reality represents a dynamic limitation (ie, of exercise) rather than a static one (ie, at rest). Recognizing that many patients are symptomatic with effort, it seems intuitive that patients should be evaluated in a dynamic fashion. Moreover, in early disease, resting hemodynamics may be normal, whereas hemodynamic evaluation during exercise may reveal clinically silent loss of pulmonary microvasculature. The use of stress echocardiography to noninvasively assess hemodynamics has been practiced for > 30 years, and reference values for exercise sPAP have been established.6 Fifteen years ago, it was shown that very large stroke volumes in varsity athletes may result in a large rise in sPAP, challenging conventional thinking.7 Bidart et al8 have demonstrated differences in the relationship between flow and pressure (pulmonary vascular resistance) in normal subjects vs subjects with pulmonary disease. Recent studies have begun to clarify the clinical correlates of exercise-induced pulmonary hypertension (PH). Invasive and noninvasive studies show that the slope of linearized mean pulmonary artery pressure-cardiac output (mPAP/Q) relationships in normal subjects should not exceed 3 mmHg/L/min.9 Estimation of PAP with treadmill exercise, or even supine bike, is technically challenging due to time constraints or motion related to exercise or tachypnea. In addition, patients may be deconditioned and, therefore, unable to exercise sufficiently. Thus, novel approaches are needed that can increase pulmonary blood flow in a titratable fashion, while echocardiography is performed. To address these challenges, in this issue of CHEST (see page 959), Lau et al10 present data that dobutamine stress echocardiography can serve well as a means to solve the issues.

Dobutamine increases cardiac output by enhancing inotropy as well as chronotropy. It also has complex effects on the vasculature, usually resulting in afterload reduction. Lau et al10 have shown that dobutamine infusion permits reliable discrimination between normal control subjects and patients with PAH based on the slope of the mPAP-Q relationship. They furthermore demonstrate that this relationship appears to be linked to the clinical status of the patient, whereby the sicker the patient, the greater the slope. A simple guide would be to expect a slope of 1 mm Hg mPAP rise for every liter increase in cardiac output in normal subjects vs a 5 mm Hg mPAP per liter increase in subjects with PH, presenting a useful discriminatory parameter for the clinician.

Although the results appear quite straightforward and attractive, there are certain limitations to this study. First, as with most PH studies, an inhomogeneous patient population complicates analysis, as patients within Dana Point class 1 PH have a variety of etiologies that may behave differently. PH related to connective tissue diseases (nine of 16 subjects in the present study) can be associated with occult left-sided diastolic dysfunction unmasked by saline challenge or exercise.11 As only resting hemodynamics were available, we do not know whether dobutamine infusion would cause an elevation of mPAP in this population based on postcapillary dysfunction from diastolic failure or inducible ischemia. In addition, all subjects were already on treatment of the pulmonary artery, and we do not know how the various therapies impact upon this relationship. Obviously, the very small number of subjects mandates validation in a larger cohort. The authors acknowledge this limitation, stating that this study was designed as a proof of concept.

Despite the above, this study adds another tool in the clinician’s armamentarium and at the same time adds a new noninvasive means of testing the right heart-pulmonary circulation axis. Clinically, if confirmed, it can represent a potential method for early diagnosis of PH in asymptomatic or minimally symptomatic individuals. Subjects at higher risk, such as those with BMPR2 abnormalities or a family history of PH, are known to have abnormal rise in PAP with exercise.6 The proposed slope by Lau et al,10 with its relationship to disease severity, can complement the findings of Grünig et al12 that prognosis is related to contractile reserve, defined as an echocardiographically demonstrated augmentation of sPAP with exercise. In the research arena, dobutamine stress echocardiography may prove to be a noninvasive surrogate to assess the capillary reserve and the ability to recruit vessels. Different responses may be seen in divergent disease states. Chronic thromboembolic PH, a larger vessel disorder, will likely have a different ability to recruit vessels as compared with PAH where microvasculature is more affected. Whatever future uses are identified, dobutamine stress testing appears to be an exciting and feasible method to study the age-old relationship between pressure, flow, and resistance.

References

Sengupta PP, Narula J. RV form and function: a piston pump, vortex impeller, or hydraulic ram? JACC Cardiovasc Imaging. 2013;6(5):636-639. [CrossRef] [PubMed]
 
McLaughlin VV, Archer SL, Badesch DB, et al; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. [CrossRef] [PubMed]
 
Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448-456. [CrossRef] [PubMed]
 
Rudski LG. Point: can Doppler echocardiography estimates of pulmonary artery systolic pressures be relied upon to accurately make the diagnosis of pulmonary hypertension? Yes. Chest. 2013;143(6):1533-1536. [CrossRef] [PubMed]
 
Rich JD. Counterpoint: can Doppler echocardiography estimates of pulmonary artery systolic pressures be relied upon to accurately make the diagnosis of pulmonary hypertension? No. Chest. 2013;143(6):1536-1539. [CrossRef] [PubMed]
 
Grünig E, Weissmann S, Ehlken N, et al. Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation. 2009;119(13):1747-1757. [CrossRef] [PubMed]
 
Bossone E, Rubenfire M, Bach DS, Ricciardi M, Armstrong WF. Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension. J Am Coll Cardiol. 1999;33(6):1662-1666. [CrossRef] [PubMed]
 
Bidart CM, Abbas AE, Parish JM, Chaliki HP, Moreno CA, Lester SJ. The noninvasive evaluation of exercise-induced changes in pulmonary artery pressure and pulmonary vascular resistance. J Am Soc Echocardiogr. 2007;20(3):270-275. [CrossRef] [PubMed]
 
Lewis GD, Bossone E, Naeije R, et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation. 2013;128(13):1470-1479. [CrossRef] [PubMed]
 
Lau EMT, Vanderpool RR, Choudhary P, et al. Dobutamine stress echocardiography for the assessment of pressure-flow relationships of the pulmonary circulation. Chest. 2014;146(4):959-966.
 
Fox BD, Shimony A, Langleben D, et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur Respir J. 2013;42(4):1083-1091. [CrossRef] [PubMed]
 
Grünig E, Tiede H, Enyimayew EO, et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation. 2013;128(18):2005-2015. [CrossRef] [PubMed]
 

Figures

Tables

References

Sengupta PP, Narula J. RV form and function: a piston pump, vortex impeller, or hydraulic ram? JACC Cardiovasc Imaging. 2013;6(5):636-639. [CrossRef] [PubMed]
 
McLaughlin VV, Archer SL, Badesch DB, et al; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-1619. [CrossRef] [PubMed]
 
Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448-456. [CrossRef] [PubMed]
 
Rudski LG. Point: can Doppler echocardiography estimates of pulmonary artery systolic pressures be relied upon to accurately make the diagnosis of pulmonary hypertension? Yes. Chest. 2013;143(6):1533-1536. [CrossRef] [PubMed]
 
Rich JD. Counterpoint: can Doppler echocardiography estimates of pulmonary artery systolic pressures be relied upon to accurately make the diagnosis of pulmonary hypertension? No. Chest. 2013;143(6):1536-1539. [CrossRef] [PubMed]
 
Grünig E, Weissmann S, Ehlken N, et al. Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation. 2009;119(13):1747-1757. [CrossRef] [PubMed]
 
Bossone E, Rubenfire M, Bach DS, Ricciardi M, Armstrong WF. Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension. J Am Coll Cardiol. 1999;33(6):1662-1666. [CrossRef] [PubMed]
 
Bidart CM, Abbas AE, Parish JM, Chaliki HP, Moreno CA, Lester SJ. The noninvasive evaluation of exercise-induced changes in pulmonary artery pressure and pulmonary vascular resistance. J Am Soc Echocardiogr. 2007;20(3):270-275. [CrossRef] [PubMed]
 
Lewis GD, Bossone E, Naeije R, et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation. 2013;128(13):1470-1479. [CrossRef] [PubMed]
 
Lau EMT, Vanderpool RR, Choudhary P, et al. Dobutamine stress echocardiography for the assessment of pressure-flow relationships of the pulmonary circulation. Chest. 2014;146(4):959-966.
 
Fox BD, Shimony A, Langleben D, et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur Respir J. 2013;42(4):1083-1091. [CrossRef] [PubMed]
 
Grünig E, Tiede H, Enyimayew EO, et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation. 2013;128(18):2005-2015. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543