Pulmonary hypertension is a challenging entity in terms of etiologic diagnosis, assessment of severity, and treatment. Pulmonary hypertension may be a primary pulmonary vascular problem (familial or idiopathic) or secondary to elevation of left-sided pressures, usually due to a left heart lesion. Importantly, long-standing secondary pulmonary hypertension can lead to vascular remodeling and arteriopathy, resulting in intrinsic pulmonary vascular disease out of proportion to the left-sided pressure elevation.
The measurement of pulmonary resistance is a commonly used method for assessing pulmonary hypertension to differentiate among the potential causes. The underlying tenet of pulmonary resistance is that flow in a circuit is proportional to the difference in the potential energy (or pressure) between two points and inversely related to the resistance across that circuit. In the cardiovascular system, resistance thus is a constant or fixed measure that describes what opposing force must be overcome for blood to move through the circulatory system (expressed as either dyn·s·cm −5 , Pa·s/m 3 , or Wood units [mm Hg/min/L]). The measurement of pulmonary resistance yields both diagnostic and prognostic data and thus is an essential component of the evaluation of any patient with known or suspected pulmonary hypertension. Thresholds or cut points for pulmonary resistance and its reactivity are routinely examined in high-impact clinical decisions, such as the need for closure of intracardiac shunts, pulmonary-specific vasodilator therapy, and cardiac transplantation.
The gold-standard method for measuring pulmonary resistance is cardiac catheterization. The principal goals of the invasive study are to confirm the presence of hypertension, ascertain the left-sided contribution, measure cardiac output, and determine the reactivity of the pulmonary hemodynamics in response to vasodilator challenge. Cardiac catheterization typically is undertaken with the patient in basal conditions or at rest but increasingly is being performed with exercise in an effort to simulate ambulatory hemodynamics. In comparison with noninvasive methods, cardiac catheterization offers the distinct advantage of absolute pressure measurement, as well as the opportunity to interrogate multiple pulmonary segments. These features are elementary in a variety of disease states (e.g., veno-occlusive disease) and help mitigate the potential for pulmonary edema from therapy specific for pulmonary hypertension. Meticulous attention should be given to the accuracy of the invasive assessment. This attention includes the use of multiple accurate methods for cardiac output determination (i.e., both thermodilution and Fick with measured oxygen consumption), oxygen confirmation of the pulmonary capillary wedge pressure, and care to avoid damping of the pulmonary artery pressure tracings. When properly performed, cardiac catheterization for pulmonary hemodynamics is safe, with an incidence of serious adverse events of <1% and a procedure-related mortality rate of 0.05%. The American College of Cardiology Foundation and American Heart Association 2009 expert consensus document on pulmonary hypertension endorses the use of cardiac catheterization in all patients with suspected or known pulmonary hypertension and states that invasive measurement of pulmonary hemodynamics must be performed in every patient before the initiation of therapy.
As an alternative to cardiac catheterization, Doppler echocardiography has been proposed as a noninvasive method for the measurement of pulmonary pressure and pulmonary resistance. In the Doppler method, pulmonary artery pressure is calculated from the peak tricuspid regurgitation velocity (TRV; in the absence of pulmonary stenosis) and then added to an estimation of right atrial pressure. Initial reports demonstrated excellent correlation of right ventricle–right atrial gradients with pulmonary systolic pressures, though these associations have been more modest in the most recent studies. Certainly, some error may be attributable to the nonsimultaneous nature of several of the studies. However, there are known limitations of the Doppler method, including difficulty obtaining the peak systolic velocity in some patients, measurements of the “feather” caused by highly sensitive systems, and the reliance on assumption of right atrial pressure.
Notably, Doppler echocardiography also has been proposed as a technique for measuring pulmonary resistance. In this noninvasive method, pulmonary resistance is ascertained by calculating and slightly modifying the ratio of peak TRV to the time-velocity integral (TVI) of the right ventricular outflow tract (RVOT) (i.e., TRV/TVI RVOT × 10 + 0.16). Thus, this method calculates a ratio of hydraulic pressure to volume and thus actually is more similar to the concept of vascular impedance. While encompassing some aspects of resistance, impedance describes how much an object resists motion when subjected to a given force. Impedance often is quantified as the ratio of force applied at a point (e.g., systolic pressure) to the resulting effect (e.g., velocity, distance, stroke volume, or volumetric flow). Prior reports have demonstrated that TRV/TVI RVOT can be used to distinguish normal from elevated pulmonary resistance, as well provide prognostic information in these patients.
In the current issue of the Journal , Abbas et al . present pooled data from 5 centers confirming the validity of TRV/TVI RVOT as a surrogate for pulmonary resistance in a relatively larger patient cohort ( n = 150). Similar to prior reports, Abbas et al . demonstrate a correlation between pulmonary resistance derived by Doppler echocardiography and that measured at cardiac catheterization, with a coefficient ( R ) of 0.76. The investigators also analyzed a modification of the equation, in which TRV is squared to help account for the quadratic relation between velocity and pressure, in an effort to improve estimates in patients with relatively higher pulmonary resistance. The result was a slight improvement in their correlation coefficient ( R = 0.79) in their study population. Using a cutoff value of 0.275, TRV/TVI RVOT had sensitivity of 83% and specificity of 89% for identifying patients with pulmonary resistance > 6 Wood units. The investigators conclude that Doppler-derived TRV/TVI RVOT (or TRV 2 /TVI RVOT ) is a reliable method for the noninvasive estimation of pulmonary resistance.
The major limitation of Doppler echocardiography is the reliance on relative rather than absolute pressure measurements. Unfortunately, for noninvasive calculation of pulmonary resistance, the reliance on relative pressure measurement is particularly susceptible to error due to the need for estimation of pressures in both atria. Of importance, the potential influence of left atrial pressure on calculation of pulmonary resistance cannot be overstated. For a given cardiac output and mean pulmonary artery pressure, a 5 mm Hg change in left atrial pressure translates to a difference of approximately 1 Wood unit in pulmonary resistance ( Figure 1 ). Left-sided disease is the most common cause of pulmonary hypertension and, if severe, poses a contraindication to therapy specific to pulmonary hypertension. Even when left atrial pressure is not included in calculations through the use of total pulmonary resistance (i.e., mean pulmonary artery pressure/cardiac output), it is noteworthy that the correlation coefficient for invasive and noninvasive data was only 0.71 in the study of Abbas et al . Mean pulmonary artery pressure is known to be tightly related ( R = 0.94) to peak pulmonary systolic pressure, which should be easily derived from the peak tricuspid regurgitant signal in patients without pulmonary stenosis. Thus, the correlation of total pulmonary resistance to echocardiography-derived data would be expected to be higher than reported. Certainly, the lack of a stronger correlation may be a reflection of nonsimultaneous acquisition in some patients, but these data again highlight some of the Doppler limitations, including the noninvasive estimation of atrial pressure.