(Chest. 2002;122:524-527.)
© 2002
American College of Chest Physicians
Electrocardiography to Define Clinical Status in Primary Pulmonary Hypertension and Pulmonary Arterial Hypertension Secondary to Collagen Vascular Disease*
Gregory S. Ahearn, MD;
Victor F. Tapson, MD, FCCP;
Abdallah Rebeiz, MD and
Joseph C. Greenfield, Jr, MD
* From the Divisions of Pulmonary and Critical Care Medicine (Drs. Ahearn and Tapson) and Cardiology (Drs. Rebeiz and Greenfield), Department of Medicine, Duke University Medical Center, Durham, NC.
Correspondence to: Victor F. Tapson, MD, FCCP, Associate Professor of Medicine, Division of Pulmonary and Critical Care, Duke University Medical Center, Box 31175, Durham, NC 27710; e-mail: tapso001{at}mc.duke.edu
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Abstract
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Study objectives: To determine the utility of the ECG for predicting clinical status in adults with primary pulmonary hypertension (PPH) or pulmonary arterial hypertension (PAH) secondary to collagen vascular disease.
Design: Retrospective study.
Setting: Outpatient clinic in a tertiary referral center.
Patients: Adult outpatients with PPH or PAH secondary to collagen vascular disease who underwent electrocardiography within 30 days of undergoing right-heart catheterization, echocardiography, and 6-min walk testing.
Interventions: None.
Measurements and results: The following measurements were recorded from each ECG: P-wave amplitude in lead II; mean frontal QRS axis; QRS duration; R-wave and S-wave deflections in leads I and V6; and the T-wave configurations in the precordial leads. These ECG variables were correlated with hemodynamic variables, RV size, and exercise capacity. Of the 61 patients included in this study, 56 (92%) were women. Eight of 61 patients (13%) had normal findings on ECGs. There was no significant difference in the demographics or hemodynamics when comparing groups with normal vs abnormal ECGs. All ECG parameters had no more than moderate correlation with hemodynamic variables, ventricular size measured by echocardiogram, and exercise capacity as measured by a 6-min walk. The best correlation was between mean the frontal QRS axis and cardiac index (r = -0.46).
Conclusions: The ECG is an inadequate screening tool to rule out the presence of clinically relevant pulmonary hypertension, either primary or secondary to collagen vascular disease. The mean frontal QRS axis correlated best with the severity of hemodynamic impairment.
Key Words: diagnosis • echocardiography • electrocardiography • exercise testing • hemodynamics • pulmonary arterial hypertension • pulmonary vascular disease
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Introduction
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Primary pulmonary hypertension (PPH) and pulmonary hypertension in the setting of collagen vascular disease (collectively called pulmonary arterial hypertension [PAH]) both result from progressive obliteration of the pulmonary vascular bed. While the pathogenesis is not understood, these uncommon conditions generally result in death from progressive right-sided heart failure. The therapy for PAH has improved1
2
; however, in some patients the disease is progressive and may require lung transplantation.3
4
5
6
It is possible that vasodilator treatment may be more effective if it is started earlier in the clinical course while the pulmonary vasculature retains some vasoreactivity. Patients with advanced PAH do not respond to acute vasodilator testing, suggesting that extensive vascular remodeling has occurred. The prognosis in this setting is poor.
The early diagnosis of PAH is difficult because presenting symptoms are often mild and nonspecific. By the time patients develop significant dyspnea, the disease is usually advanced. Accurate diagnosis depends on right-heart catheterization; however, this is an invasive and costly test and, thus, is not appropriate for screening. Right ventricular (RV) dysfunction and pulmonary hypertension often are diagnosed serendipitously by echocardiography; however, echocardiography may not detect pulmonary hypertension unless the diagnosis is specifically sought or if there is not adequate tricuspid regurgitation. The latter scenario may occur in up to 10% of patients with pulmonary hypertension (Ahearn and Tapson; unpublished data). The ECG is easily performed, is inexpensive, and is widely available. Its diagnostic utility has been established for ischemic heart disease, but it has not been widely evaluated as a screening tool with which to exclude pulmonary vascular disease associated with PAH.
Previous studies7
have suggested that ECG parameters may be predictive of the severity of RV dysfunction in patients with pulmonary emboli. Also, changes in ECG parameters reflect improvement in RV function after single-lung transplantation.8
The role of the ECG has not been well-established in evaluating patients with PAH, perhaps because of its perceived clinical utility. Thus, we sought to determine the sensitivity of standard ECG parameters of RV hypertrophy (RVH) in a cohort of patients with PAH. Furthermore, we hypothesized that the degree of ECG abnormalities may be predictive of hemodynamic parameters, echocardiographic findings, and exercise capacity.
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Materials and Methods
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Sixty-one patients with PPH or pulmonary hypertension secondary to collagen vascular disease were identified retrospectively. The diagnosis of PPH or pulmonary hypertension was established according to standard criteria.9
Only patients who had undergone echocardiograms and cardiac catheterizations within 30 days of undergoing a 12-lead ECG were included in this study. Right-heart catheterizations were performed according to standard procedures. Cardiac outputs were calculated using the estimated Fick principle. Pulmonary vascular resistance (PVR) was calculated using standard formulas and was expressed as Wood units. All echocardiograms included standard two- dimensional parasternal (long-axis and short-axis views), apical (2-chamber and 4-chamber views), and subcostal windows. Peak RV systolic pressures were estimated from tricuspid regurgitation jet velocities as assessed by continuous-wave Doppler echocardiography. All ECGs were read by an attending cardiologist who was blinded to the clinical status of the patient. The amplitude of the P wave in lead II, QRS axis, QRS duration, R-wave/S-wave ratios in leads I and V6, and the T-wave configuration in the precordial leads. "Positive" was defined as the major deflection above the isoelectric point, "negative" was defined as being the predominant deflection below the isoelectric point, and "equivocal" was defined as having no predominant deflection. The isoelectric point was defined as the PR interval. The configuration of the QRS complex in lead V1 was recorded as Q, QR, R, RS, or RSR'. The magnitude of each of these deflections was recorded. The R and S waves in lead I and lead V6 were recorded. RVH was defined as present if the frontal plane QRS axis was 
80°, if the R-wave/S-wave ratio in lead V1 was > 1, and the R wave in lead V1 was > 0.5 mV.
Statistical Analysis
Relationships between the ECG parameters and the hemodynamic and echocardiogram parameters are expressed as Spearman correlation coefficients. Hemodynamic data were analyzed using nonparametric analysis because it was not normally distributed. A p value of < 0.05 was considered to be significant. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy all were calculated using standard formulas.
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Results
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Of the 61 patients studied, 56 (92%) were women. Baseline patient information is presented in Table 1
. Eight of 61 ECGs (13%) were read as being completely normal. There was a trend toward lower PVR and pulmonary artery pressure as well as toward a higher cardiac index in patients who had normal ECG findings; however, there were no significant differences in this limited patient sample.
Correlations of selected ECG parameters with hemodynamic, echocardiographic, and exercise capacity are shown in Table 2
. No ECG parameter correlated well with hemodynamic or echocardiographic findings. The amplitude of the P wave in lead II had a negative correlation, with cardiac index of 0.3. It correlated poorly with other hemodynamic, echocardiographic, and exercise parameters, with correlation coefficients ranging from 0.26 to 0.39. The frontal QRS axis correlated best of all the ECG parameters with hemodynamic and echocardiographic parameters. It correlated best with cardiac index, with a coefficient of -0.46 (Fig 1
). Other correlation coefficients ranged from 0.38 to 0.42. Frontal QRS axis correlated poorly with the 6-min walk distance (r = 0.15). QRS duration was poorly correlated with all the parameters that were tested, as was the R-wave/S-wave ratio in lead V6. The R-wave/S-wave ratio in lead I correlated moderately with the cardiac index (r = 0.49), but only moderately to poorly with other hemodynamic, echocardiographic, and exercise parameters. The presence of an inverted T wave in lead V4 was not predictive of hemodynamic, echocardiographic, or exercise parameters. When ECGs that had been read as normal were excluded from the analysis, the correlations did not improved (data not shown).
Defining a cutoff value of > 100° for the frontal QRS axis as abnormal, Table 3
depicts the sensitivity, specificity, PPV, and NPV for detecting hemodynamic, echocardiographic, and exercise results. A QRS axis of > 100° was 89% sensitive for detecting RV enlargement. It was 100% specific for a PVR of > 5 Wood units and was 83% specific for RV enlargement. The sensitivity and specificity were moderate for mean pulmonary artery pressure (MPAP) and cardiac index. The sensitivity and specificity were poor for the 6-min walk distance. The PPV for MPAP of > 50 mm Hg, PVR of > 5 Wood units, and RV enlargement were 84%, 100%, and 97%, respectively. The PPV was poor for patients with a cardiac index of < 2.0 L/min and a 6-min walk distance of < 1,000 feet. The NPV of a QRS axis of > 100° was greatest for a cardiac index of < 2.0 L/min at 79%.
Using RVH, as judged by a blinded attending cardiologist, Table 4 shows sensitivity, specificity, PPV, and NPV for detecting hemodynamic, echocardiographic, and exercise results. The sensitivity was uniformly poor. A reading of RVH was 83% specific for both PVR of > 5 Wood units and RV enlargement. The PPV was excellent for PVR of > 5.0 Wood units and RV enlargement. The PPV for an MPAP of > 50 mm Hg was 81%. The NPV was greatest for RV enlargement (84%).
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Discussion
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An elevated right atrial (RA) pressure is an ominous finding in patients with PAH and is predictive of mortality.10
11
12
A markedly elevated RA pressure, however, occurs late in the course of the disease when there is marked functional impairment. Ideally, ECG parameters would be both sensitive and specific in identifying patients early in the course of the disease when symptoms are mild. It is possible that therapy would be more efficacious if instituted early in the course of the disease before there has been irreversible damage to the pulmonary vasculature.
The most striking result of our study is that 13% of patients with significant pulmonary hypertension who had been referred to a tertiary medical center had normal ECG findings, which cast serious doubt on the utility of the ECG as a general screening tool. Compared with patients with abnormal ECG findings, there was a trend toward less severe pulmonary hypertension. Small numbers limit the statistical power of the analysis. Furthermore, our results show that traditional ECG measures of RVH do not correlate well with derangement of the pulmonary circulation and do not correlate well with exercise capacity as measured by 6-min walk distance. The frontal plane QRS axis correlated the best of all the parameters tested. Interestingly, when patients with normal ECGs were removed from the analysis, there was no improvement in the correlation between the QRS axis and the severity of pulmonary hypertension.
When defining a cutoff of > 100°, the sensitivities were still low (Table 2)
; however, a QRS axis of > 100° was highly predictive of RV enlargement and a PVR of > 5 Wood units, suggesting that this finding is of diagnostic value. Similarly, the presence of RVH had a PPV of 96% for an elevated PVR. The sensitivity and specificity were inadequate for other parameters (Table 3)
.
Kanemoto13
reported that an R wave in lead V1 of > 1.2 mV was 93% sensitive for detecting a systolic MPAP of > 90 mm Hg. However, this parameter was relatively nonspecific (47%). Kanemoto also found no more than moderate correlation between the R waves and S waves in leads V1 and V6 and the hemodynamic parameters.
In a series of patients with pulmonary hypertension secondary to mitral stenosis, Gupta et al14
found that there was a moderate correlation between the mean QRS axis and pulmonary artery pressure (r = 0.51). They were able to distinguish three groups. Patients with a mean QRS axis of < 70° were unlikely to have elevated MPAP. Almost all patients with a QRS axis of > 100° had moderate-to-severe pulmonary hypertension. In our series, all patients had pulmonary hypertension, so it is not possible to calculate such a cutoff. However, we found a similar correlation between QRS axis and MPAP.
In conclusion, the frontal plane QRS axis is the ECG parameter that correlates the best with severity of hemodynamic derangement. The magnitude of the correlation, however, is only moderate. A QRS axis of > 100° is highly predictive of RV enlargement. The ECG will have a limited role in ruling out PPH or pulmonary hypertension secondary to collagen vascular disease. It is important to note that these findings should not be extrapolated to evaluating PAH from other causes such as mitral stenosis, left ventricular dysfunction, or parenchymal lung disease.
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Footnotes
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Abbreviations: MPAP = mean pulmonary artery pressure; NPV = negative predictive value; PAH = pulmonary arterial hypertension; PPH = primary pulmonary hypertension; PPV = positive predictive value; PVR = pulmonary vascular resistance; RA = right atrial; RV = right ventricle ventricular; RVH = right ventricular hypertrophy
Received for publication August 13, 2001.
Accepted for publication January 16, 2002.
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Abstract
Introduction
