Cardiopulmonary Hemodynamics in Pulmonary Hypertension: Pressure Tracings, Waveforms, and More (2008)

The most recent pulmonary hypertension (PH) classification divides PH into 5 categories based on pathophysiology and clinical characteristics.1 As part of the diagnostic workup of PH, the current guidelines recommend performing a right heart catheterization (RHC) with a pulmonary artery catheter (PAC).2 A RHC provides valuable diagnostic information, especially to discriminate between the first 2 categories: pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH).A diagnosis of PAH is established in the presence of a resting mean pulmonary arterial pressure (PAP) greater than 25 mmHg and a left atrial or left ventricular (LV) filling pressure of no more than 15 mmHg.1 The same mean PAP value cutoff and a left-sided filling pressure of greater than 15 mmHg fulfills criteria for a diagnosis of PVH. On the other hand, clear distinction between PAH and PVH can be problematic, and may be improved by additional maneuvers.Several hemodynamic numbers routinely obtained during a RHC provide prognostic value in idiopathic PAH, including right atrial pressure (RAP), mean PAP, and cardiac index. For example, a baseline RAP greater than 20 mmHg carries a 6-month mortality rate of almost 100% without treatment.3 Other interventions performed during the initial RHC provide additional hemodynamic information that helps guide treatment decisions and clarifies the etiology of the patient's PH.Some of these interventions include an acute vasodilator challenge to determine the presence of vasoreactivity or an exercise or fluid challenge.45 This article reviews characteristics of hemodynamic and waveform measurements. In addition, evaluation of data that includes cardiac outputs or indices, stroke volume or arteriovenous oxygen differences, mixed venous oxygen saturations, and others to define a profile of cardiopulmonary physiology is emphasized.A national registry sponsored by the National Institutes of Health proposed the hemodynamic definition for primary pulmonary hypertension as mean PAP of at least 25 mmHg and a left heart filling pressure of no more than 12 mmHg.6The left heart filling pressure cutoff that determines PH as being precapillary in nature (eg, PAH) has been subsequently increased from 12 mmHg to no more than 15 mmHg.1 While these criteria are fairly well established and applied, the methodology to measure those values is less standardized. For example, a potential for significant discrepancy between left-heart filling pressure numbers determined by left ventricular (LV) end-diastolic pressure versus pulmonary capillary wedge pressure has been found.7In this study, approximately 40% of patients with PH whose pulmonary capillary wedge pressure was no more than15 mmHg were found to have LV end-diastolic pressure greater than 15 mmHg, therefore affecting their classification status. Likewise, the methodology for the measurement of right heart pressures can vary between practitioners. Some groups measure it at the end of exhalation; others measure them during a breath hold maneuver; and still others rely on the electronic pressures obtained by catheterization laboratory software.The influence of intrathoracic pressure on intracardiac pressure measurement is least at end expiration. Therefore, intracardiac measurements should be recorded at end expiration when intrathoracic pressure is near zero.8In order to obtain retrograde transmission of left atrial events through the pulmonary capillary bed (pulmonary capillary wedge pressure measurement), the PAC tip must be located in a lung segment where pulmonary venous pressure exceed the alveolar pressure (physiologic zone 3).89 Most of the lung is in zone 3 in the supine patient and the catheter tip will be naturally directed to this zone.Evidence of distinct A and V waves indicates the catheter tip is in zone 3. Conditions such as hypovolemia, advanced parenchymal lung disease, or positive pressure ventilation will make the alveolar pressure exceed the pulmonary venous pressure, therefore creating zones 1 or 2. In this case, pulmonary capillary wedge pressure becomes a measure of alveolar pressure rather than left atrial pressure. Distinct A and V waves are less likely to appear in zones 1 or 2.8The pulmonary artery catheter education project (www.pacep.org)—an outstanding internet-based program endorsed by most critical care societies—has outlined guidelines for a more accurate and consistent measurement of right heart pressures. The program recommends obtaining all measurements at the end of exhalation. For adequate and accurate measurement of RAP and pulmonary capillary wedge pressure, identification of a distinct A wave is ideal.The A wave occurs with atrial contraction. Since pulmonary capillary wedge pressure records the backward reflection of the left atrial contraction, the timing of the A wave is delayed. It is found near the end or after the QRS complex on the electrocardiogram (EKG) tracing. The V wave occurs when blood fills the atria as the tricuspid or mitral valve is closed. During pulmonary capillary wedge pressure measurement, the V wave is usually found well after the T wave of the EKG tracing.Figure 1 shows the recommended methodology to estimate pulmonary capillary wedge pressure. Identification of A and V waves with respect to the EKG is crucial. The next step is to identify the inhalation and exhalation segments. Tracings on Figure 1 correspond to spontaneous breathing. Pulmonary capillary wedge pressure (and all other waveforms) should be measured during exhalation. The Pulmonary Artery Catheter Education Project (PACEP) program recommends finding the beginning of the pressure decline (right before going into inhalation), locating the A wave just prior to the decline, then measuring the top and bottom of the A wave values, and averaging these values.Whenever needed, some maneuvers can be performed to confirm adequate position of the catheter tip and wedge pressure measurement, including a chest X ray, bedside fluoroscopic evaluation, or an oxygen (O2) saturation measurement from blood drawn from the distal port of the PAC while wedged (slow blood draw). In this case, if the catheter tip is properly wedged, the blood O2 saturation should be very close to a simultaneous blood sample of the patient's systemic arterial saturation. PAP should also be measured at the end of expiration (Figure 2).A prominent V wave could potentially influence the measurement of pulmonary capillary wedge pressure and lead to a higher pressure estimate. Such a large V wave typically occurs in the presence of significant mitral valve regurgitation or impaired LV compliance (Figure 3). When the latter is present, administration of a systemic vasodilator trial (eg, nitroprusside) can lead to acute and dramatic resolution of the prominent V wave and significant reduction or normalization of the A wave.On the other hand, in the presence of impaired relaxation of the LV, maneuvers that transiently increase venous return and/or pulmonary vasodilation (eg, exercise challenge, fluid bolus, pulmonary vasodilator trial) can lead to a rapid increase in LV filling pressure. This will manifest itself by an increase in the amplitude of the A wave and especially the V wave during pulmonary capillary wedge pressure measurement (Figure 4). Such a rapid V wave increase would suggest the presence of left ventricular diastolic dysfunction (LVDD) being unmasked by those maneuvers. The patient in Figure 4 had risk factors for LVDD. However, his baseline pulmonary capillary wedge pressure was normal and a vasodilator trial with nitric oxide was performed, which led to a large pressure increase in the V wave. This trial unmasked impaired relaxation of the LV. His normal pulmonary capillary wedge pressure at rest is possibly explained by a lower intravascular volume after diuretic use.In clinical practice, determination of cardiac output and cardiac index is typically done by either the thermodilution method or Fick method (using the Fick principle). Normal values are: cardiac output, 4 to 8 L/minute; cardiac index, 2.6 to 4.2 L/minute/m2. A low cardiac index has been shown to offer prognostic value for patients with PAH.3 However, assessment of cardiac index alone would potentially neglect the impact of heart rate on cardiac output/cardiac index numbers. Therefore, the stroke volume index (cardiac index/heart rate) should also be calculated and assessed. In the Table, both patients have identical cardiac index numbers but stroke volume index for patient B is twice as high, which suggests better right ventricle (RV) myocardial performance. Assessment of stroke volume index values is also important when comparing hemodynamic numbers before and after PH therapy. Even in cases where the cardiac index does not change much, a significant increase in stroke volume index would still suggest improved RV function.In this method, cold or room-temperature solution is injected in the right atrium through the proximal port of the PAC.8 A thermistor near the catheter tip measures pulmonary arterial (PA) temperature continuously and detects the transient drop in PA temperature after the solution injection. A curve is generated by plotting the decline in PA temperature (°C) versus time (seconds). The area under the curve (AUC) is measured by the cardiac output computer and a cardiac output is provided (L/min). The AUC is inversely related to the cardiac output (eg, higher area, lower cardiac output) because the injected solution is diluted by body temperature blood flow. Some practical limitations to values obtained by this method in patients with PH include severe tricuspid regurgitation and presence of a congenital heart defect (eg, atrial septal defect). In general, the injections are performed in triplicate and averaged to yield the cardiac output measurements.The Fick method measures pulmonary blood flow using principles described by Adolph Fick in 1870. In the absence of a significant intracardiac shunt, the pulmonary and systemic blood flows are equal. The Fick equation is:This formula shows that arteriovenous oxygen difference is inversely proportional to cardiac output. For more accurate results, the Fick method requires documentation of both O2 consumption and arteriovenous oxygen difference.8 Ideal determination of O2 consumption can be done by collecting the patient's exhaled air over several minutes, something that is not practical in the catheterization laboratory or intensive care unit. Metabolic carts at bedside can be used to estimate O2 consumption using indirect calorimetry. This approach requires strict attention to detail. Finally, O2 consumption can be assumed as basal (125 mL of O2/min/m2). While this is the more practical approach to calculate cardiac output by the Fick method, one must keep in mind that when assuming OO2 consumption as basal, one may underestimate this value in critically ill patients. Calculation of arteriovenous oxygen difference requires simultaneous determination of arterial and mixed venous O2. Using an estimated arterial oxygen saturation obtained by pulse oximetry in this formula could lead to potential inaccurate calculations and direct measurement from arterial blood should be considered. See additional discussion on arteriovenous oxygen difference below.The literature indicates significant discrepancy between these 2 methods, especially on both low and high output states. Recent studies have specifically compared these 2 methods in patients with PH and did not find major discrepancies.1011 Some caveats to keep in mind when using either method, include:Even though cardiac index offers more relevant information than cardiac output, one must keep in mind that large changes in body weight (eg, secondary to fluid retention) could affect the body surface area calculation and therefore affect cardiac index values over time (cardiac index = cardiac output / body surface area). This applies to cardiac index estimates by both the thermodilution method and the Fick method.Based on the current referral pattern seen at most PH centers—large number of patients with underlying left heart disease—it can be quite difficult to discriminate between idiopathic PAH and PH secondary to left heart disease. Close observation of additional hemodynamic numbers and tracings can provide the necessary clues to make this distinction more accurate.This intervention is typically performed to assess the presence of a reversibility component, which suggests a potential benefit from calcium-channel blockers.4 The indication for this challenge mainly applies to patients in whom idiopathic PAH is suspected. Pulmonary vasodilators such as nitric oxide or intravenous prostacyclins are the agents more commonly used. When performing this trial, the clinician must keep in mind that these agents could lead to an acute increase in right-to-left blood flow and potentially overload a poorly compliant LV. Their use in patients with elevation of the LV filling pressures can lead to dangerous situations, including acute pulmonary edema.1314Close inspection should be given to LV end-diastolic pressure and pulmonary capillary wedge pressure values and waveforms during a vasodilator trial. The patient in Figure 4 had risk factors for left ventricle diastolic dysfunction (LVDD). However, the resting pulmonary capillary wedge pressure was normal, which was suggestive of precapillary PH or PAH and a vasodilator trial with nitric oxide was performed. In this case, nitric oxide led to a significant increase in both LV end-diastolic pressure and pulmonary capillary wedge pressure which unmasked the presence of impaired relaxation of the LV. Even though the baseline pulmonary capillary wedge pressure was within normal limits, the wedge pressure changes seen with nitric oxide suggested PVH to be the most likely diagnosis. A dramatic V wave pressure increase was also consistent with this diagnosis.This intervention is used by many PH centers during the hemodynamic evaluation of patients with suspected PH.1516 Unfortunately, the protocol for exercise challenge is not standardized. Nevertheless, detailed assessment of LV end-diastolic pressure and pulmonary capillary wedge pressure values and waveforms during an exercise challenge can provide very useful information when trying to determine the presence of PAH versus PVH.In addition to a greater than 25 mmHg cutoff to establish the presence of PH at rest, the guidelines also propose a PH diagnosis if mean PAP is greater than 30 mmHg during an exercise challenge.17 A limitation of the exercise-induced diagnostic criterion is that it does not address what are the expected simultaneous changes in LV filling pressure (eg, pulmonary capillary wedge pressure) to differentiate between PAH or PVH.Figure 5 reveals a significant increase in mean PAP consistent with the exercise-related PH definition. However, LV end-diastolic pressure increased in concordance with the increase in pulmonary artery diastolic pressure (no pulmonary artery diastolic pressure–LV end-diastolic pressure gradient appreciated here), which suggests that the increase in mean PAP to greater than 30 mmHg is secondary to a retrograde increase of LV filling pressure. This is consistent with impaired LV relaxation probably unmasked by increased venous return during an exercise challenge. In this case scenario, initiation of pulmonary vasodilators would likely be contraindicated since they could lead to an increase in the patient's LV filling pressure, putting the patient at risk for pulmonary congestion and worsening dyspnea. This potential risk is reinforced by the fact that the use of PAH therapies in patients with LV systolic dysfunction has led to a higher frequency of congestive heart failure.18–21Figure 6 reveals a mean PAP greater than 30 mm Hg after an exercise challenge but the LV filling pressure remains relatively normal. An increased gradient is appreciated between her pulmonary artery diastolic pressure and left ventricular enddiastolic pressure at peak exercise suggesting the presence of true PAH. This scenario is perhaps more suggestive of early PAH changes unmasked with an exercise challenge, especially in this patient with underlying systemic sclerosis. Unfortunately, the literature is not clear on how to approach or treat exercise-induced PAH. Many PH experts consider initiation of treatment with PAH-approved therapies in this case.Similar findings to the ones described above (vasodilator and exercise challenge) can be seen when a fluid challenge is administered. A typical amount of fluid infused varies between 500 to 1000 cc of normal saline. Documenting a significant increase in LV filling pressure (LV end-diastolic pressure or pulmonary capillary wedge pressure) or significant changes in pulmonary capillary wedge pressure waveforms after such challenge would increase the likelihood that a diagnosis of PVH is present (Figure 7).Before newer and safer vasodilator agents became available (eg, nitric oxide), systemic vasodilator agents such as nitroprusside were used to assess for pulmonary vasoreactivity of patients with PAH.22 This agent has also been used in patients with significant LV systolic dysfunction before heart transplant consideration.23 However, its role in assessing vasoreactivity of patients with PVH secondary to LVDD is less clear.At our institution, this agent is frequently used to assess hemodynamic response in cases where PVH is suspected but where the distinction between PAH and PVH is not completely clear. Its use has not been validated in prospective studies and the available experience is based on case series.24 Having said that, in select cases it can provide a dramatic reduction or normalization of pressures that confirms the presence of LVDD as the cause of the patient's PH. This can be quite important, especially in cases where the patient has been labeled as “PH out of proportion to left heart disease.” Given the potential for abrupt systemic vasodilation, it is our practice to perform nitroprusside vasodilator trials while simultaneously monitoring LV end-diastolic pres- sure and systemic arterial pressures. We do not perform nitroprusside trials in clear-cut PAH cases or in cases where there is evidence of RV dysfunction. Those patients may have an impaired hemodynamic response and may not be able to adequately increase their cardiac output in the event of systemic hypotension. For such cases, other safer alternatives such as an exercise challenge or a fluid bolus could be considered in order to evaluate the LV pressure response to extra circulating volume or an increase in blood flow. Unfortunately, none of those interventions has been validated.Documenting normalization or near normalization of pulmonary pressures while maintaining or increasing cardiac output provides additional evidence to suspect PVH as the main cause for the patient's PH. Such distinction is obviously crucial given the significant difference in the treatment approach for both groups. Figure 3 depicts how the administration of nitroprusside led to normalization of pulmonary pressures. Mean pulmonary capillary wedge pressure also normalized and the V wave had a dramatic decrease in amplitude, which suggests improvement in LV relaxation.Mixed venous oxygen saturation determines the oxygen saturation of blood returning to the lungs before reaching the alveolo-capillary units. It is best measured from the distal lumen of a catheter in the pulmonary artery. A normal value is A value lower than this (eg, probably a low cardiac output that has led to increased of oxygen by the in mixed venous oxygen saturation numbers and after likely improvement in cardiac output and cardiac index. Given the value of cardiac index as a of in PAH, an increase in mixed venous oxygen saturation the that the response is before one on this information, one to keep in mind that mixed venous oxygen saturation measures oxygen and it can be by several of them is oxygen which will typically oxygen saturation of arterial blood and this in will lead to some additional increase of mixed venous oxygen saturation. Therefore, a rapid increase in mixed venous oxygen saturation could be related to a higher of oxygen without an improvement in cardiac output/cardiac in mixed venous oxygen saturation values can have a more significant impact on treatment decisions when both measurements and after an are obtained on the same O2. into both arterial and mixed venous O2 saturation and oxygen can provide a more accurate of the cardiac output is the amount of oxygen by from of blood The value is obtained from venous oxygen from the arterial oxygen and is mainly by cardiac output/cardiac index. For example, a low cardiac output should lead to lower mixed venous oxygen saturation values the venous oxygen and a higher difference between O2 and O2 will be Therefore, a high arteriovenous oxygen difference a lower cardiac output. The O2 difference calculation that with 100% oxygen oxygen difference oxygen saturation mixed venous oxygen Normal mL of the presence of limitations to determine cardiac output/cardiac index in patients with tricuspid regurgitation the thermodilution method or inaccurate estimate of O2 consumption the Fick of O2 difference values provides an additional and estimate of cardiac output/cardiac index. O2 difference is compared before and after PAH this will be more when and treatment arterial oxygen saturation and O2 used in the calculations are normal arterial oxygen saturation is to and normal venous oxygen saturation is a normal resting O2 difference is 3 to 5 mL of mL of A number higher than this suggests a low cardiac output/cardiac index and Unfortunately, these values mainly to values in the normal or will affect the normal heart catheterization is routinely performed as part of the diagnostic workup of patients with suspected PH. have mainly on the more hemodynamic values that assess pressures and pulmonary capillary wedge pressure. the increase in of patients with underlying left heart to PH centers for evaluation, PH experts are with significant in trying to discriminate between precapillary and PH observation of the hemodynamic response and change in waveforms at rest and after such as pulmonary fluid and may provide information to an of cardiopulmonary treat PH are therefore to at the catheterization tracings to confirm the the and these data with additional information such as mixed venous oxygen or arteriovenous oxygen when the of the cases at most PH an accurate diagnosis of PH and it is an that requires of the diagnostic and value of interventions or frequently performed during initial PH is crucial in order to a more consistent and approach to these