Background
In patients with pulmonary arterial hypertension (PAH), the mechanical complications of pulmonary artery (PA) enlargement are related to sudden cardiac death (SCD). The aim of this study was to investigate the prevalence of PA enlargement, the correlation of main PA (MPA) diameter with other echocardiographic parameters, and the role of transthoracic echocardiography in screening for such complications.
Methods
Among 298 patients who were followed for PAH, patients with PA enlargement (>40 mm) by transthoracic echocardiography were consecutively enrolled in a prospective manner. The presence of left main and airway compression, PA dissection, or PA thrombus was determined with cardiac computed tomography.
Results
Forty-six patients (15.4%; mean age, 49 ± 14 years; 32.6% men) with dilated MPAs were enrolled. Mechanical complications were present in 16 patients (34.8%). Those with complications had more dilated MPAs compared with patients without (mean PA diameter, 55.6 ± 12.2 vs 46.7 ± 4.3 mm; P = .012). Other echocardiographic parameters of the right heart, such as right ventricular systolic pressure, showed no differences ( P > .05 for all). The area under the receiver operating characteristic curve for MPA diameter was 0.750 (95% CI, 0.577–0.923; P = .009), with the highest sensitivity and specificity values for the presence of complications being 85.7% and 58.6%, respectively, according to an MPA diameter of 46.5 mm.
Conclusions
Mechanical complications related to sudden cardiac death in patients with PAH with dilated PAs are common. The overall performance of transthoracic echocardiography as a screening tool for predicting such complications appears reasonable. Given the burden of sudden cardiac death, measurement of PA diameter should be routinely included over the course of follow-up, especially in patients with PAH.
Sudden cardiac death (SCD) is a prominent cause of mortality in patients with pulmonary arterial hypertension (PAH). Dilatation of the pulmonary artery (PA) due to progression of PAH has been proposed as a potential mechanism that provokes extrinsic compression of the left main coronary artery (LMCA), which can subsequently lead to potential arrhythmogenic left ventricular ischemia and eventual SCD. Notably, PA dilatation could also provoke dissection of the PA with fatal pericardial tamponade.
Although transthoracic echocardiography (TTE) is routinely performed typically 6 months apart over the course of follow-up in patients with PAH, the diameter of the PA is yet to receive such attention. The procedure for measuring the main PA (MPA) diameter and its cutoff values for diagnosing dilatation were not reported in the 2010 American Society of Echocardiography guidelines on right heart quantification, nor in the 2015 American Society of Echocardiography guidelines on cardiac chamber quantification. Consequently, little is known about the PA trunk diameter, which warrants investigation for assessing related complications and the prevalence of mechanical complications associated with PAH.
Therefore, in this study we sought to investigate the prevalence of mechanical complications of dilated PA related to SCD in patients with PAH. Specifically, we evaluated (1) extrinsic LMCA compression, (2) PA dissection, (3) PA thrombosis, and (4) airway compression, using cardiac computed tomography (CT) as a reference, along with identifying the echocardiographic predictors of such complications.
Methods
Population and Study Protocol
Study participants were initially screened among 298 patients who were followed for PAH with any etiology in the PAH center at Severance Hospital (Seoul, South Korea). Diagnosis of PAH was confirmed by right heart catheterization (RHC) according to European guidelines in all participants. From November 2014 to August 2015, patients with dilated PAs (i.e., ≥40 mm) by baseline or follow-up TTE were consecutively enrolled and underwent subsequent cardiac CT in a prospective manner. The appropriate institutional review committee approved the study protocol, and written informed consent was obtained from each patient. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee. The etiology of PAH, clinical data set, echocardiographic parameters, parameters of most recent RHC, and history of PAH-specific treatments were collected at the time of enrollment.
TTE
Echocardiographic examinations were performed using commercially available equipment (Vivid S6; GE Medical Systems, Milan, Italy). Maximal diameter of the MPA was determined on a parasternal short-axis pulmonary bifurcation view at end-diastole on the QRS deflection using inner edge–to–inner edge measurement methods ( Figure 1 ). To optimize visualization of the MPA, particularly the anterior border of the MPA, the echocardiographic transducer was occasionally tilted superiorly from the standard parasternal short-axis view.
After obtaining standard M-mode, two-dimensional, and Doppler images of the left ventricle and left atrium, assessment of right heart function, including basal and midcavity right ventricular (RV) dimension, maximal velocity of tricuspid regurgitation (TR), the Tei index, RV systolic pressure (RVSP), TR area, left ventricular eccentricity index, tricuspid annular plane systolic excursion (TAPSE), RV outflow tract acceleration time and velocity-time integral, stroke volume, and tricuspid annular systolic velocity (S′), was performed in accordance with American Society of Echocardiography guidelines. Right atrial pressure was estimated using inferior vena cava diameter, and RV pressure was calculated (RVSP = 4[TR maximal velocity) 2 + right atrial pressure).
Cardiac CT
Data acquisition was conducted using a second-generation dual-source CT scanner (Somatom Definition Flash; Siemens Healthcare, Forchheim, Germany) with a prospectively electrocardiographically gated axial technique. Scans were performed during full inspiration when possible. Intravenous contrast (Pamiray [370 mg/mL iodine]; Dongkook Pharma, Seoul, South Korea) was used. Deidentified data sets were transferred to a workstation (Vitrea version 6.5.3; Vital Images, Minnetonka, MN).
The presence of mechanical complications was determined on the basis of the anatomy of cardiac CT as a reference: (1) extrinsic LMCA compression, (2) PA dissection, (3) PA thrombosis, and (4) airway compression. Patients were classified into two groups: those with and those without complications according to the presence of any of the four complications on cardiac CT. The image analysis was carried out by two experienced physicians, and a joint reading was performed to reach a consensus in the case of a disagreement.
Statistical Analysis
Categorical variables are presented as numbers (with proportions), and continuous variables are expressed as mean ± SD. For continuous variables, Student’s t test was used. Differences between categorical variables were analyzed using the χ 2 test or the Fisher exact test, as appropriate. Correlations between PA diameters and other variables were assessed using the Spearman R method. Linear regression was used to examine the relationship between MPA diameter and other hemodynamic parameters. Univariate logistic regression was performed to estimate predictors of complications. Receiver operating characteristic analysis was performed to assess the usefulness of MPA diameter in predicting the presence of complications. Two-sided P values < .05 were considered to indicate statistical significance, with 95% CIs. Statistical analyses were performed using SPSS version 20 (SPSS, Chicago, IL).
Results
Baseline Characteristics and Primary Outcomes
In total, 46 patients (mean age, 49 ± 14 years; 15 [32.6%] men) were identified as having dilated PAs by TTE. Among the study population, 16 patients (34.8%) were found to have mechanical complications of PAH by cardiac CT. Specifically, extrinsic LMCA compression by MPA was detected among 15 patients (32.6%), airway compression was present in two patients (4.3%), and thrombus in the PA was found in three patients (8.7%) by cardiac CT. Comparisons of baseline clinical and hemodynamic characteristics between patients with and without complications are reported in Table 1 . Functional capacity or physical activity as assessed by 6-min walking distance did not differ materially between groups. Patients with complications presented with a higher mean PA pressure compared with those without complications (68 ± 21 vs 53 ± 15 mm Hg, P = .012).
| Characteristic | Total population ( n = 46) | Patients without mechanical complications ( n = 30) | Patients with mechanical complications ( n = 16) | P |
|---|---|---|---|---|
| Age (y) | 49 ± 14 | 51 ± 14 | 47 ± 15 | .367 |
| Male gender | 15 (32.6%) | 8 (26.7%) | 7 (43.8%) | .239 |
| 6-min walking distance (m) | 432 ± 86 | 432 ± 82 | 431 ± 99 | .977 |
| WHO functional class | 2.0 ± 0.0 | 2.2 ± 0.4 | 2.3 ± 0.5 | .301 |
| Duration of illness (y) | 8.3 ± 9.1 | 8.6 ± 9.3 | 7.9 ± 8.9 | .817 |
| Etiology of PAH | .034 | |||
| Idiopathic PAH | 12 (26.1%) | 10 (33.3%) | 2 (12.5%) | |
| APAH: CTD | 4 (8.7%) | 4 (13.3%) | 0 (0%) | |
| APAH: portal HTN | 1 (2.2%) | 1 (3.3%) | 0 (0%) | |
| APAH: CHD, not repaired | 18 (39.1%) | 7 (23.3%) | 11 (68.8%) | |
| APAH: CHD, repaired | 11 (23.9%) | 8 (26.7%) | 3 (18.8%) | |
| PAH-specific medication | 43 (95.6%) | 29 (96.7%) | 15 (93.8%) | .999 |
| Anticoagulation | 3 (6.7%) | 2 (6.7%) | 1 (6.7%) | .999 |
| Pulmonary hemodynamics | ||||
| Mean PAP (mm Hg) | 58 ± 19 | 53 ± 15 | 68 ± 21 | .012 |
| Mean PCWP (mm Hg) | 11 ± 6 | 11 ± 7 | 10 ± 3 | .612 |
| PVR (dyne · sec · cm −5 ) | 721 ± 414 | 706 ± 431 | 1,002 ± 430 | .312 |
| Cardiac output (L/min) | 4.8 ± 1.0 | 4.7 ± 1.1 | 5.2 ± 0.5 | .485 |
Dyspnea or dyspnea on exertion was documented in 19 patients (41.3%), while six patients (13.0%) reported atypical angina. Typical angina with or without complications was not reported in this study. Targeted therapy was implemented among 44 patients (95.7%), while 20 patients (43.5%) were treated with a combination strategy. Laboratory results, including hematocrit, creatinine, and N-terminal pro–B-type natriuretic peptide, displayed no differences between the two groups ( P > .05 for all).
Echocardiographic Findings
As shown in Table 2 , the mean diameter of the MPA was 51.0 ± 9.0 mm, and the MPA was more dilated in patients with complications than those without (55.6 ± 12.2 vs. 46.7 ± 4.3 mm, P = .012). In the assessment of the right heart, patients with complications had wider TR areas compared with those without complications (8.43 ± 5.97 vs. 4.92 ± 4.25 cm 2 , P = .032). Notably, other parameters, including basal and midcavity RV dimension, TAPSE, RV outflow tract acceleration time, RV outflow tract velocity-time integral, S′, Tei index, left ventricular eccentricity index, and RVSP, revealed no significant differences.
| Variable | Total population ( n = 46) | Patients without mechanical complications ( n = 30) | Patients with mechanical complications ( n = 16) | P |
|---|---|---|---|---|
| MPA diameter (mm) | 51.0 ± 9.0 | 46.7 ± 4.3 | 55.6 ± 12.2 | .012 |
| LV ejection fraction (%) | 67 ± 9 | 68 ± 8 | 65 ± 10 | .313 |
| Calculated RVSP (mm Hg) ∗ | 87 ± 31 | 84 ± 29 | 93 ± 35 | .332 |
| Basal RV dimension (mm) | 48 ± 7 | 47 ± 6 | 50 ± 9 | .317 |
| Midcavity RV dimension (mm) | 42 ± 8 | 40 ± 7 | 44 ± 9 | .123 |
| TR maximal velocity (m/sec) | 4.25 ± 0.99 | 4.20 ± 0.75 | 4.34 ± 1.34 | .689 |
| TR area (cm 2 ) | 6.06 ± 5.08 | 4.92 ± 4.25 | 8.43 ± 5.97 | .032 |
| Tei index | 0.56 ± 0.17 | 0.54 ± 0.17 | 0.59 ± 0.17 | .396 |
| LV eccentricity index | 1.71 ± 1.39 | 1.84 ± 1.65 | 1.43 ± 0.35 | .387 |
| TAPSE (cm) | 2.11 ± 2.61 | 2.28 ± 3.16 | 1.75 ± 0.56 | .534 |
| RVOT acceleration time (msec) | 158.0 ± 39.9 | 160.0 ± 31.4 | 154.0 ± 54.3 | .649 |
| RVOT VTI | 16.9 ± 6.4 | 17.6 ± 7.0 | 15.5 ± 5.0 | .344 |
| S′ (m/sec) | 10.9 ± 2.8 | 11.5 ± 2.7 | 9.9 ± 2.5 | .068 |
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