Adenosine Stress Testing In Pulmonary Hypertension
- Literature Highlights -

1.  2004.  Jones AT et al. Quantifying pulmonary perfusion in primary pulmonary hypertension using electron-beam computed tomography. Eur Respir J 2004; 23: 202–207. (National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Royal Brompton Hospital, London, UK.)

1. Following the placement of radial arterial (Abbocath, Abbott, Ireland) and pulmonary artery (Arrow International, Reading, PA, USA) catheters,
2. a period of 20 min was allowed to reach a haemodynamic steady state.
3. An intravenous infusion of adenosine commenced (5, 10, 30, 50, 100, 150, 200 mcg/kg/min.
4. via the infusion port of the pulmonary artery catheter,
5. each dose being administered for a period of 3–5 min.
6. Pulmonary and systemic haemodynamic data were recorded at baseline and during steady state conditions at the end of each dosing interval.
7. Pulmonary artery occlusion pressure was estimated following inflation of the catheter balloon, values being taken at end-expiration and averaged over three respiratory cycles.
8. Cardiac output measurements were taken in triplicate, each following an injection of 10 mL of 5% dextrose at room temperature, and averaged.
9. Vascular resistances were calculated using standard equations.
10. A positive vasodilator response was defined as a 20% decrease in pulmonary vascular resistance (PVR).
11. The dose of adenosine was increased until a positive response was obtained, the patient suffered side effects (chest discomfort, flushing) or there was a clinically relevant fall in systemic arterial pressure.
     

2.  2009.  McLaughlin VV, et al. 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; 1573-1619.

1. The diagnosis of PAH requires confirmation with a complete right heart catheterization (RHC).
2. Essential Components of Invasive Hemodynamic Assessment:  Oxygen saturations (SVC, IVC, RV, PA, SA); Right atrial pressure; Right ventricular pressure; Pulmonary artery pressure, systolic, diastolic, mean; Pulmonary arterial wedge pressure, left atrial pressure, or left ventricular end-diastolic pressure; Cardiac output/index; Pulmonary vascular resistance; Systemic blood pressure; Heart rate; Response to acute vasodilator.
3. The current hemodynamic definition of PAH is a mean pulmonary artery pressure (mPAP) greater than 25 mm Hg; a pulmonary capillary wedge pressure (PCWP), left atrial pressure, or left ventricular end-diastolic pressure (LVEDP) less than or equal to 15 mm Hg; and a pulmonary vascular resistance (PVR) greater than 3 Wood units.
4. Acute vasodilator testing, which involves the administration of pharmacologic agents to test the presence of pulmonary vasoreactivity, has prognostic value and should be performed in all IPAH patients who might be considered potential candidates for long-term calcium-channel blocker therapy.
5. Those with overt right heart failure or hemodynamic instability should not undergo acute vasodilator testing.
6. For purposes of identifying patients likely to respond to chronic calcium channel blocker therapy,  definition of an acute responder is a reduction in mPAP of at least 10 mm Hg to an absolute mPAP of less than 40 mm Hg without a decrease in cardiac output.
7. Vasodilator testing should be performed by centers with experience in the administration of these agents and the interpretation of the results.
8. Acute vasodilator testing is not indicated, and may be harmful, in patients with significantly elevated left heart filling pressures. 
9. Link to the PDF
10. Link to the page that contains the PDF document's (very helpful) Tables and Figures.

3.  2008.  Park, MH. Advances in Diagnosis and Treatment in Patients With Pulmonary Arterial Hypertension. Catheterization and Cardiovascular Interventions 71:205–213 (2008). (Division of Cardiology, Director of Pulmonary Vascular Disease Program, University of Maryland School of Medicine, Baltimore, MD)

1. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive increase in pulmonary artery pressure and pulmonary vascular resistance, leading to right ventricular failure and death. It is defined as a sustained elevation of mean pulmonary arterial pressure of >25 mm Hg at rest or >30 mm Hg with exercise, with a pulmonary capillary wedge pressure of <15 mm Hg and a pulmonary vascular resistance of >3 Wood units.
2. Right heart catheterization remains the gold standard by which the diagnosis of PAH is made. The information from right heart catheterization serves three important roles.
3. First, it confirms the diagnosis of PAH by demonstrating pulmonary artery pressure elevation in the presence of a normal pulmonary capillary wedge pressure (<15 mm Hg), which is essential to exclude pulmonary venous hypertension. The echocardiogram, although useful as a screening test, can overestimate or underestimate the pulmonary artery pressures.
4. Second, the right heart catheterization provides important prognostic information. Several studies over the years have confirmed the finding of the PPH Registry data, which identified elevated right atrial pressure and decreased cardiac index as indicators of poor prognosis.
5. Third, a vasodilator testing can be performed with the initial right heart catheterization when appropriate.
6. The current definition of a responder is defined as a reduction of mean pulmonary artery pressure (mPAP) by at least 10 mm Hg to a value of 40 mm Hg or less with stable cardiac output (see Conventional Treatment).
    

4.  1992.  Schrader BJ, et al. Comparison of the effects of adenosine and nifedipine in pulmonary hypertension. J Am Coll Cardiol 1992 Apr; 19(5): 1060-4. (Department of Pharmacy Practice, University of Illinois, Chicago)

1. The hemodynamic effects of intravenously administered adenosine, a potent vasodilator, were examined in 15 patients with pulmonary hypertension.
2. All patients were given adenosine, 50 micrograms/kg per min, increased by 50 micrograms/kg per min at 2 min intervals to a maximum of 500 micrograms/kg per min or until the development of untoward side effects.
3. The patients were then given oral nifedipine, 20 mg every hour, until a greater than or equal to 20% decrease in pulmonary vascular resistance or systemic hypotension occurred.
4. The administration of maximal doses of adenosine, 256 +/- 46 micrograms/kg per min, produced a 2.4% reduction in pulmonary artery pressure (p = NS), a 37% decrease in pulmonary vascular resistance (p less than 0.001) and a 57% increase in cardiac index (p less than 0.001).
5. The administration of maximally effective doses of nifedipine (91 +/- 36 mg) produced a 15% reduction in the mean pulmonary artery pressure (p less than 0.05), a 24% decrease in pulmonary vascular resistance (p less than 0.01) and an 8% increase in cardiac index (p = NS).
6. There was a significant correlation (r = 0.714, p = 0.01) between the reduction in pulmonary vascular resistance that resulted from adenosine administration and that achieved with the administration of nifedipine.
    

5. 1992.  GA Haywood GA, et al. Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy. Circulation 1992; 86; 896-902. (Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK.)

“All patients received 30% oxygen via face mask throughout the study. Arterial oxygen saturations were measured at baseline and during drug infusions. Diamorphine 2.5 mg and diazemuls 2.5-5 mg were given intravenously to relax without markedly sedating the patient before right heart catheterization.” p. 897

“When hemodynamic parameters had remained stable over a period of 15 minutes, the drug infusion was administered via a fourth lumen in the pulmonary flotation catheter so that the drug was delivered into the right atrium. Hemodynamic measurements were repeated between 5 and 10 minutes after the start of the infusion, when steady-state hemodynamics had been reached. The duration of the adenosine infusion was between 10 and 15 minutes.” p.898

“In this study, the agent that resulted in the greatest fall in transpulmonary pressure gradient was adenosine 100 mcg/kg/min. This fall (35%) occurred as a result of a rise in pulmonary capillary wedge pressure that was not transmitted back across the pulmonary vasculature to result in an equivalent rise in mean pulmonary artery pressure. The mean value for pulmonary artery pressure was unchanged by the infusion of adenosine 100 mcg/kg/min.” p.899 [Please note: The patients in this study had biventricular failure.]

6.  2002.  Scharf AM et al. Hemodynamic Characterization of Patients with Severe Emphysema.  American Journal of Respiratory and Critical Care Medicine 2002; 166:314-322. (Pulmonary and Critical Care Division, University of Maryland, Baltimore)

1. Right heart catheterization was performed at rest with patients supine.
2. Oxygen was given if needed to achieve saturation > 92%.
3. Right atrial (RA), right ventricular, pulmonary arterial (PA), pulmonary wedge (Pw), systemic arterial pressures, arterial and mixed venous O₂ saturations, and cardiac output by thermodilution were measured.
4. All pressures were taken at end-expiration.
5. Mean PA pressures were calculated from end-expiratory PA pressures (mean PA = PA_diastolic + [pulse pressure/3]).  Pulmonary vascular resistance (PVR) was calculated as PVR = [(PA mean – Pw)/CO] x 79.9 (dynes-sec-cm^-5).   Link to PubMed

7.  2010.  Silvestry, FE: Swan-Ganz catheterization: Interpretation of tracings. UpToDate. Last literature review version 18.1: January 2010 | This topic last updated: February 12, 2009. (Hospital of the University of Pennsylvania)

8. 1995.  Bergstra A, et al. Assumed oxygen consumption based on calculation from dye dilution cardiac output: an improved formula.  European Heart Journal (1995) 16, 698-703. (Department of Cardiology, Thorax Center, University Hospital, Department of Medical Physiology, University of Groningen, The Netherlands)

“VO2 (assumed) = ((157.3 * BSA) + (10 * Sex) – (10.5 * LN Age) + 4.8) ml per min

where BSA = body surface area, Sex = 1 for males, 0 for females, LN Age=the natural logarithm of the patient’s age.

The constant, 1.36, is the amount of oxygen (ml at 1 atmosphere) bound per gram of hemoglobin. The exact value of this constant varies from 1.34 to 1.39, depending on the reference and the way it is derived. The constant 0.0031 represents the amount of oxygen dissolved in plasma at 1 atmosphere. The dissolved oxygen term generally can be ignored, but becomes significant at high pressures -- as in a hyperbaric chamber.