Naoko Kawata

Role of 320-Slice CT Imaging in the Diagnostic Workup of Patients With Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Right-sided heart catheterization (RHC) and pulmonary digital subtraction angiography (PDSA) are the standard methods used in diagnosing suspected or defi nite chronic thromboembolic pulmonary hypertension (CTEPH). We studied the ability of 320-slice CT imaging to detect simultaneously chronic thromboembolic fi ndings in the pulmonary arteries and pulmonary hemodynamics based on the curvature of the interventricular septum (IVS) in CTEPH . METHODS Forty-four patients with high clinical suspicion of CTEPH underwent RHC, PDSA, and enhanced double-volume retrospective ECG-gated 320-slice CT scan. We measured the sensitivity and specificity of CT imaging to detect thrombi in the pulmonary arteries compared with PDSA. We also compared IVS bowing (expressed as curvature) measured on the short-axis cine heart image with pulmonary arterial pressure (PAP) obtained by RHC. RESULTS Compared with PDSA, the sensitivity and specificity of CT imaging to detect chronic thromboembolic findings were 97.0% and 97.1% at the main/lobar level and 85.8% and 94.6% at the segmental level, respectively. The correlation coefficients of IVS curvature with systolic PAP and mean PAP were 2 0.79 ( P , .001) and 2 0.86 ( P , .001), respectively. CONCLUSIONS The use of 320-slice CT imaging allows for less invasive and simultaneous detection of thrombi and evaluation of pulmonary hemodynamics for the diagnostic work-up of CTEPH.

Home-based pulmonary rehabilitation in patients with inoperable or residual chronic thromboembolic pulmonary hypertension: A preliminary study

BACKGROUND Management of chronic thromboembolic pulmonary hypertension (CTEPH) has recently improved because of advances in pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and disease-targeted medications. However, patients with inoperable CTEPH or persistent pulmonary hypertension (PH) after these interventions continue to exhibit impaired exercise capacity and limited quality of life (QOL). METHODS Eight patients with inoperable or residual CTEPH (mean age, 64±12 years; WHO functional class II/III, 6/2; mean pulmonary artery pressure, 47±13 mmHg) in stable condition and receiving disease-targeted medications participated in a 12-week home-based pulmonary rehabilitation program (muscle strength training, respiratory exercises, and walking) with supervised hospital sessions from March 2012 to January 2014. Efficacy parameters were prospectively evaluated at baseline and at completion of the 12-week program. RESULTS After completion of the pulmonary rehabilitation program, the 6-minute walking distance (6MWD) (33.3±25.1 m), St. George׳s Respiratory Questionnaire activity score, quadriceps force, and 7-day physical activity level were significantly improved compared with baseline. All subjects completed the rehabilitation program. Although one patient experienced presyncope during the in-hospital exercise sessions, no other severe adverse events or complications of pulmonary rehabilitation were observed. CONCLUSIONS These findings suggest that home-based pulmonary rehabilitation with closely supervised sessions may safely improve exercise capacity, leg muscle strength, general activity in daily life and health-related QOL in CTEPH patients.

Quantitative assessment of cross-sectional area of small pulmonary vessels in patients with COPD using inspiratory and expiratory MDCT

OBJECTIVES Structural and functional changes in pulmonary vessels are prevalent at the initial stages of chronic obstructive pulmonary disease (COPD). These vascular alterations can be assessed using cross-sectional area (CSA) of small pulmonary vessels. However, neither in non-COPD smokers nor in COPD patients it has been defined whether the structural changes of pulmonary vessels detected by paired inspiratory and expiratory CT scans are associated with emphysematous changes. We quantified the CSA and low attenuation area (LAA) and evaluated the changes in these parameters in the inspiratory and expiratory phases. MATERIALS AND METHODS Fifty consecutive non-COPD smokers and COPD patients were subjected to multi detector-row CT and the percentage of vessels with a CSA less than 5 mm(2) as well as the percentage LAA for total lung area (%CSA<5, %LAA, respectively) were calculated. RESULTS The %CSA<5 correlated negatively with %LAA. The %CSA<5 was lower in COPD patients with emphysema as compared with non-COPD smokers and COPD patients with or without mild emphysema. In addition, the %CSA<5 was lower in the no/mild emphysema subgroup as compared with non-COPD smokers. The respiratory phase change of %CSA<5 in COPD patients was greater than that in non-COPD smokers. CONCLUSION The percentage of small pulmonary vessels decreased as emphysematous changes increase, and this decrease was observed even in patients with no/mild emphysema. Furthermore, respiratory phase changes in CSA were higher in COPD patients than in non-COPD smokers.

Clinical, physiological, and radiological features of asthma-chronic obstructive pulmonary disease overlap syndrome

Background Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is associated with rapid decline in lung function, poorer health-related quality-of-life outcomes, and frequent exacerbations, compared to COPD alone. Although the numbers of patients with ACOS have increased, there is little established evidence regarding diagnostic criteria and treatment options. Thus, the aim of our study was to clarify the clinical, physiological, and radiological features of patients with ACOS. Methods We examined a total of 100 patients with COPD and 40 patients with ACOS, who were selected based on clinical criteria. All patients underwent baseline testing, including a COPD assessment test, pulmonary function tests, and multidetector row computed tomography imaging. Percentage of low attenuation volume, percentage of wall area, and percentage of total cross-sectional area of pulmonary vessels less than 5 mm2 (%CSA <5) were determined using multidetector row computed tomography. ACOS patients were administered a fixed dose of budesonide/formoterol (160/4.5 μg, two inhalations; twice daily) for 12 weeks, after which the ACOS patients underwent multidetector row computed tomography to measure the same parameters. Results At baseline, the ACOS patients and COPD patients had a similar degree of airflow limitation, vital capacity, and residual volume. ACOS patients had higher COPD assessment test scores, percentage of wall area, and %CSA <5 than COPD patients. Compared to baseline, budesonide/formoterol treatment significantly increased the forced expiratory volume in 1 second and decreased the degree of airway wall thickness (percentage of wall area) as well as pulmonary microvascular density (%CSA <5) in ACOS patients. Conclusion Our results suggest that ACOS is characterized by an airway lesion–dominant phenotype, in contrast to COPD. Higher %CSA <5 might be a characteristic feature of ACOS.

The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. OBJECTIVE The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. METHODS Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. RESULTS In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. CONCLUSIONS A significant correlation exists between airway parameters and FEV1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

Electrocardiogram-gated 320-slice multidetector computed tomography for the measurement of pulmonary arterial distensibility in chronic thromboembolic pulmonary hypertension.

Background We aimed to study whether pulmonary arterial distensibility (PAD) correlates with hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) using electrocardiogram (ECG)-gated 320-slice multidetector computed tomography (MDCT). Methods and Findings ECG-gated 320-slice MDCT and right heart catheterization (RHC) was performed in 53 subjects (60.6±11.4 years old; 37 females) with CTEPH. We retrospectively measured the minimum and maximum values of the cross sectional area (CSA) of the main pulmonary artery (mainPA), right pulmonary artery (rtPA), and left pulmonary artery (ltPA) during one heartbeat. PAD was calculated using the following formula: PAD = [(CSAmaximum−CSAminimum)/CSAmaximum]×100(%). The correlation between hemodynamic parameters and PAD was assessed. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were 40.8±8.7 mmHg and 8.3±3.0 wood units, respectively. PAD values were as follows: mainPA (14.0±5.0%), rtPA (12.8±5.6%), and ltPA (9.7±4.6%). Good correlations existed between mainPAD, with mPAP (r = −0.594, p<0.001) and PVR (r = −0.659, p<0.001). The correlation coefficients between rtPAD and ltPAD with pulmonary hemodynamics were all lower or equal than for mainPAD. Conclusions PAD measured using ECG-gated 320-slice MDCT correlates with pulmonary hemodynamics in subjects with CTEPH. The mainPA is suitable for PAD measurement.

Association of deep vein thrombosis type with clinical phenotype of chronic thromboembolic pulmonary hypertension.

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) has been considered to be caused by single or recurrent pulmonary embolism (PE) arising from deep vein thrombosis (DVT). In Japan, female predominance and association of HLA-B*5201 with CTEPH unrelated to DVT were reported. In acute PE residual proximal DVT is associated with larger obstruction of pulmonary arteries. However, it remains uncertain whether DVT and the type of DVT are associated with clinical phenotype of CTEPH. PURPOSE To clarify the association of DVT and DVT type with clinical phenotype of CTEPH. METHODS Among 98 consecutive patients who underwent 16 or 64-slice multidetector CT angiography and indirect venography, 91 patients (66% female, age: 56±3 years) with adequate images were enrolled. The associations of DVT and DVT type with pulmonary hemodynamics, CT obstruction index and other clinical parameters were analyzed. RESULTS DVT was found in 45 patients (49.5%) (distal: 12, proximal: 33), and was significantly associated with male gender and recurrent type. Furthermore, it was more frequent in HLA-B*5201-negative, and d-dimer positive patients. Compared with distal DVT, proximal DVT was associated with male gender, larger CT obstruction index (48.6±13.0 vs. 34.1±13.2%, p=0.004), and higher mean pulmonary arterial pressure (48.2±12.8 vs. 40.8±7.9 mmHg, p=0.03). Proximal DVT was significantly associated with the central type of CTEPH only in HLA-B*5201-negative patients. CONCLUSIONS The existence and type of DVT were associated with clinical phenotype of CTEPH, and proximal DVT might contribute to the central type of CTEPH in only HLA-B*5201-negative patients.

Noninvasive assessment of pulmonary vascular resistance by echocardiography in chronic thromboembolic pulmonary hypertension

BACKGROUND Pulmonary vascular resistance (PVR) is an important parameter in the management of patients with chronic thromboembolic pulmonary hypertension (CTEPH), and numerous noninvasive methods for PVR prediction have been proposed. However, a systematic evaluation of the methods that are specific for CTEPH has not been conducted. We compared a variety of echocardiography-derived prediction indices with direct right heart catheterization (RHC) to identify the most reliable noninvasive indicator of PVR in patients with CTEPH. PATIENTS AND METHODS Echocardiography and RHC were performed sequentially in 40 patients (mean age: 62.4±11.4 years; 30 females) with CTEPH. We measured the peak flow velocity of tricuspid regurgitation (TRV), tricuspid regurgitation pressure gradient (TRPG), right ventricular outflow tract (RVOT) time-velocity integral (TVIRVOT), left ventricular outflow tract (LVOT) time-velocity integral (TVILVOT), cardiac output at RVOT (CORVOT), and the LVOT (COLVOT) using echocardiography. The parameters TRV/TVIRVOT, TRV/TVILVOT, TRV/CORVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were then calculated to predict the PVR. Finally, correlations between these echocardiographic predictors of PVR and the PVR data obtained from RHC (PVRRHC) were assessed. RESULTS The mean pulmonary arterial pressure and PVRRHC were 32.1±11.4mmHg and 5.4±2.9 Wood units, respectively. TRV/TVIRVOT, TRV/TVILVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were all significantly correlated with the PVRRHC, and TRPG/COLVOT was the most strongly correlated with the PVRRHC (r=0.807, p<0.001). CONCLUSIONS Echocardiographic measurement of TRPG/COLVOT is a reliable noninvasive predictor of PVR in CTEPH patients.

Effect of threshold on the correlation between airflow obstruction and low attenuation volume in smokers assessed by inspiratory and expiratory MDCT.

Background The estimation of emphysematous changes is very sensitive to computed tomography (CT) threshold level. In clinical practice, the predetermined threshold is usually set at −950 Hounsfield units (HU) for the detection of low attenuation volume (LAV). However, threshold levels that are tightly connected to pulmonary function abnormalities have not been determined. Purpose To determine the threshold level for calculating an LAV that closely reflects airflow limitation in patients with chronic obstructive pulmonary disease (COPD). Material and Methods Seventy-six consecutive non-COPD smokers and COPD patients underwent paired inspiratory and expiratory multidetector CT (MDCT). LAV% was segmented every 10 HU between −1000 and −750 HU to examine the correlation between LAV% and indexes of obstructive impairment. Results LAV% gradually increased as the threshold level increased on both inspiratory and expiratory images. LAV% on inspiratory images was higher than that on expiratory images at all threshold levels between −1000 and −750 HU. The threshold level that correlated with obstructive impairment differed between the two images: −930 HU on inspiratory and −870 or −880 HU on expiratory images. Conclusion LAV% dramatically changed according to the threshold level on both inspiratory and expiratory images, indicating that LAV% is dependent on the attenuation threshold level in patients with COPD. The threshold linking LAV% to airflow limitation was higher on expiratory than on inspiratory images.

Longitudinal changes in structural abnormalities using MDCT in COPD: do the CT measurements of airway wall thickness and small pulmonary vessels change in parallel with emphysematous progression?

Background Recent advances in multidetector computed tomography (MDCT) facilitate acquiring important clinical information for managing patients with COPD. MDCT can detect the loss of lung tissue associated with emphysema as a low-attenuation area (LAA) and the thickness of airways as the wall area percentage (WA%). The percentage of small pulmonary vessels <5 mm2 (% cross-sectional area [CSA] <5) has been recently recognized as a parameter for expressing pulmonary perfusion. We aimed to analyze the longitudinal changes in structural abnormalities using these CT parameters and analyze the effect of exacerbation and smoking cessation on structural changes in COPD patients. Methods We performed pulmonary function tests (PFTs), an MDCT, and a COPD assessment test (CAT) in 58 patients with COPD at the time of their enrollment at the hospital and 2 years later. We analyzed the change in clinical parameters including CT indices and examined the effect of exacerbations and smoking cessation on the structural changes. Results The CAT score and forced expiratory volume in 1 second (FEV1) did not significantly change during the follow-up period. The parameters of emphysematous changes significantly increased. On the other hand, the WA% at the distal airways significantly decreased or tended to decrease, and the %CSA <5 slightly but significantly increased over the same period, especially in ex-smokers. The parameters of emphysematous change were greater in patients with exacerbations and continued to progress even after smoking cessation. In contrast, the WA% and %CSA <5 did not change in proportion to emphysema progression. Conclusion The WA% at the distal bronchi and the %CSA <5 did not change in parallel with parameters of LAA over the same period. We propose that airway disease and vascular remodeling may be reversible to some extent by smoking cessation and appropriate treatment. Optimal management may have a greater effect on pulmonary vascularity and airway disease than parenchymal deconstruction in the early stage of COPD.