Right Ventricular Dyssynchrony in Patients With Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC. CONCLUSIONS: CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Comparative clinical and predictive value of lung perfusion blood volume CT, lung perfusion SPECT and catheter pulmonary angiography images in patients with chronic thromboembolic pulmonary hypertension before and after balloon pulmonary angioplasty.

OBJECTIVES: Lung perfusion blood volume (PBV) using dual-energy computed tomography has recently become an accepted technique for diagnosing pulmonary thromboembolism. We evaluated the correlation among lung PBV, single-photon emission computed tomography (SPECT) and catheter pulmonary angiography images in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after balloon pulmonary angioplasty (BPA). METHODS: In total, 17 patients and 57 sessions were evaluated with the three modalities. Segmental lung perfusion and its improvement in lung PBV and SPECT were compared with catheter pulmonary angiography as the reference standard before and after BPA. RESULTS: The sensitivity for detecting segmental perfusion defects using SPECT and lung PBV was 85% and 92%, the specificity was 99% and 99%, the accuracy was 92% and 95%, the positive predictive value was 99% and 99%, and the negative predictive value was 88% and 93%. The sensitivity for detecting segmental perfusion improvement using SPECT and lung PBV was 61% and 69%, the specificity was 75% and 83%, the accuracy was 62% and 70%, the positive predictive value was 97% and 98%, and the negative predictive value was 12% and 16%. CONCLUSIONS: Lung PBV is a useful technique for evaluation of segmental lung perfusion and its improvement in patients with CTEPH. KEY POINTS: • BPA is a new treatment for patients with CTEPH. • Lung PBV images may be more sensitive for pulmonary blood flow. • The current work demonstrates that Lung PBV images are useful in evaluating patients with CTEPH. • The current work demonstrates that Lung PBV is useful in gauging the treatment effect of BPA.

Correlation between lung perfusion blood volume and SPECT images in patients with chronic thromboembolic pulmonary hypertension by balloon pulmonary angioplasty.

OBJECTIVES: We evaluated the reperfusion by balloon pulmonary angioplasty (BPA) in lung PBV and SPECT images. METHODS: In total, 17 patients and 57 sessions were evaluated. Pre-BPA and post-BPA lung PBV and SPECT/CT images, based on both anatomical segments and physiologic regions (upper/middle/lower) were compared. RESULTS: BPA had a positive effect on most hypoperfused/unperfused segments/regions. There was generally a high rate of agreement between PBV measurements and SPECT/CT. CONCLUSIONS: BPA shows promise as a treatment modality for CTEPH patients. SPECT/CT, and, to a lesser extent, PBV, were useful in indicating areas in need of balloon angioplasty.

Deeper S Wave in Lead V5 and Broader Extent of T Wave Inversions in the Precordial Leads are Clinically Useful Electrocardiographic Parameters for Predicting Pulmonary Hypertension.

Electrocardiography (ECG) is used to screen for pulmonary hypertension (PH). However, it is unclear which parameters of ECG are the most useful for screening.ECG parameters related to right ventricular hypertrophy criteria were examined in 145 ECGs of subjects who were suspected to have PH and underwent right heart catheterization (RHC) (age 58.4 ± 17.5 years, 112 women, mean pulmonary arterial pressure [MPAP] 35.4 ± 13.3 mmHg). Based on the results of RHC, 108 subjects had PH (56 pulmonary arterial hypertension [PAH] and 52 chronic thromboembolic pulmonary hypertension [CTEPH]).Fourteen of 17 ECG parameters in the present study were significantly associated with PH on univariate analysis. On multivariable logistic regression analysis, S wave depth in lead V5 (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.10-1.47) and depth of T wave inversion in lead V4 (OR 1.21, 95% CI 1.03-1.46) were independent predictors of MPAP ≥ 25 mmHg, and the cut-off values determined by receiver operating characteristic curve analyses were 0.42 mV and -0.28 mV, respectively.In conclusion, a deeper S wave in lead V5 and the presence of a wider extent of negative T waves in the precordial leads may be clinically simple and useful ECG parameters for screening for PH.

Balloon pulmonary angioplasty is effective for treating peripheral-type chronic thromboembolic pulmonary hypertension in elderly patients.

AIM: Balloon pulmonary angioplasty (BPA) has recently been established as an effective therapy for peripheral-type chronic thromboembolic pulmonary hypertension (CTEPH). However, the safety and effectiveness of BPA in elderly patients with CTEPH have not been clarified. METHODS: A total of 19 patients with CTEPH who underwent BPA were recruited. The patients were assigned to groups by age, <70 years (non-elderly; n = 11) and ≥70 years (elderly; n = 8). Hemodynamic parameters, right ventricular function and plasma N-terminal pro-brain natriuretic peptide were assessed before and after BPA, and complications arising after BPA were also evaluated. RESULTS: Hemodynamic parameters and right heart function did not differ significantly between the two groups at baseline. BPA significantly improved pulmonary arterial pressure, pulmonary vascular resistance and fractional area change in both groups (all P < 0.05), although the differences were comparable. No fatal complications developed, but the frequency of minor complications, such as transient hemoptysis, was higher in the elderly group than in the non-elderly group (median 0.45 [interquartile range 0.27-0.63] vs 0 [0-0.33], respectively; P = 0.021). The frequency of such complications was also higher in patients with a psychiatric disorder than in those without (0.50 [0.44-1.00] vs 0.14 [0-0.33], respectively; P = 0.006). Multivariate regression analysis identified higher age, baseline N-terminal pro-brain natriuretic peptide values and an underlying psychiatric disorder as significant predictors of complications of BPA. CONCLUSIONS: BPA is an effective treatment for peripheral-type CTEPH regardless of age; however, higher age, N-terminal pro-brain natriuretic peptide values before treatment and an underlying psychiatric disorder might be associated with minor complications. Geriatr Gerontol Int 2018; 18: 678-684.

Cardiac Calcified Amorphous Tumors in a Patient with Hemodialysis for Diabetic Nephropathy.

Calcified amorphous tumor (CAT) is a rare, non-neoplastic tumor involving calcium deposition in amorphous materials. Although its etiology is unknown, cases have frequently been reported in patients with hemodialysis for chronic kidney disease. We herein describe a case of cardiac CAT in a 64-year-old woman who had been on hemodialysis for diabetic nephropathy for 20 years, and the findings of the present patient, in association with the findings of previous case reports, suggest that end-stage renal disease seems to play an important role in the onset of CAT, especially in CAT formation at the mitral annulus, which appears to differ from CAT occurring at other sites.

The Histological Features of a Myocardial Biopsy Specimen in a Patient in the Acute Phase of Reversible Catecholamine-induced Cardiomyopathy due to Pheochromocytoma.

A 63-year-old Japanese woman with an adrenal tumor was transferred to our hospital due to cardiogenic shock. Right and left ventriculography showed severe hypokinesis of the middle segment and the apex in both ventricles, and an endomyocardial biopsy demonstrated a small number of necrotic myocytes and cellular infiltration. She was diagnosed with pheochromocytoma and quickly recovered after treatment with an α-blocker. The functional disability of both the right and left ventricles with less myocardial damage due to an excessive level of catecholamine seemed to be related to the early recovery the present patient with catecholamine-induced cardiomyopathy due to pheochromocytoma.

Penetration of inferior vena cava filter strut through an introducer sheath inserted from the left internal jugular vein: An anatomical pitfall.

The report describes a case of penetration of an inferior vena cava filter (IVCF) strut through an introducer sheath inserted from the left internal jugular vein. A 64-year-old woman was admitted to our hospital with pulmonary embolism and lower extremity deep vein thrombosis. We attempted to implant a retrievable type IVCF via the left internal jugular vein. However, an unexpected resistance occurred during the advancement of the filter after passing the first few inches within the 8-Fr introducer sheath. Immediately, we checked the insertion site using fluoroscopy, which demonstrated penetration of the filter struts to the outside of the sheath. We speculate that a strong angulation in the vessel from the left internal jugular to superior vena cava might have contributed to this rare complication. .

Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after balloon pulmonary angioplasty (BPA): Preliminary results.

OBJECTIVES: Balloon pulmonary angioplasty (BPA) is a treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Its effect on pulmonary perfusion has not been quantified; we examined the clinical significance of pulmonary blood volume (PBV) using dual-energy computed tomography (DECT) in patients with CTEPH undergoing BPA. METHODS: In this retrospective study of 16 BPAs in eight female patients with CTEPH, we evaluated both-lung (n=16), right- or left-lung (n=32), and three right- or left-segment (upper, middle, and lower) (n=96) PBVs before and after BPA, using DECT. We evaluated the relationships between improvement in lung PBV and pulmonary artery (PA) pressure (PAP), cardiac index (CI), pulmonary vascular resistance (PVR), and 6-min walking distance. We measured PA enhancement (PAenh) on DECT images and calculated lung PBV/PAenh to adjust timing. RESULTS: Pre- and post-BPA 6-segment lung PBV/PAenh were 0.067±0.021 and 0.077±0.019, respectively, in the treated segment (p<0.0001). There were significant positive correlations between pre- to post-BPA improvements in both-lung PBV/PAenh and PAP (R=0.69, p=0.005), PVR (R=0.56, p=0.03), and 6-min walking distance (R=0.67, p=0.01). CONCLUSIONS: Improved PBV after BPA, reflecting increased lung perfusion, was positively correlated with PAP, PVR, and 6-min walking distance. Lung PBV may be an indicator of BPA treatment effect.

Diverse Findings in Calcified Thrombus Between Histopathology and In Vivo Imaging Including Intravascular Ultrasound, Optical Coherence Tomography, and Angioscopy.

A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy.

Coronary Artery Pseudoaneurysm due to Medial Mucoid Degeneration Mimicking an Intra-atrial Mass.

Coronary artery aneurysms are frequently asymptomatic and may be difficult to diagnose by cardiac imaging. We herein present a case of a coronary artery aneurysm of the right coronary artery due to medial mucoid degeneration mimicking an intra-atrial mass on echocardiography and magnetic resonance imaging, with the cause being diagnosed after surgery.

Impact of Catheter Sheath Insertion into the Radial Artery on Vascular Endothelial Function Assessed by Reactive Hyperemia Peripheral Arterial Tonometry.

The transradial approach has been used for coronary procedures, but this procedure carries a risk of injury to the endothelium of the radial artery. In this study, the vascular dysfunction caused by transradial catheterization was examined using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently developed technique for assessing endothelial function in digits, and the differences in injuries were compared according to the size of sheath.Forty-three patients undergoing transradial catheterization with 6-Fr sheaths (n = 17) or 4-Fr/5-Fr (non-6-Fr; n = 26) sheaths underwent RH-PAT using an Endo-PAT2000 before, the day after, and 6 months after catheterization. RH-PAT was assessed in the arm of sheath placement and in the other arm as a control.RH-PAT values decreased from 2.42 ± 0.67 before catheterization to 2.08 ± 0.41 the day after catheterization in the 6-Fr group (P = 0.031); this was more evident in patients with a longer procedure time (> 91 minutes). In contrast, the change in the non-6-Fr group was not significant. RH-PAT of the non-catheterized arm was unchanged in both groups. At 6 months after catheterization, RH-PAT values in the 6-Fr group had not completely returned to baseline.In conclusion, the insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function assessed by RH-PAT the day after the procedure and was sustained for 6 months. Thus, the use of smaller size sheaths (< 6-Fr) with a shorter procedure should be considered when performing transradial catheterization.

iMap-Intravascular Ultrasound Radiofrequency Signal Analysis Reflects Plaque Components of Optical Coherence Tomography-Derived Thin-Cap Fibroatheroma.

BACKGROUND: The ability of iMap-intravascular ultrasound (IVUS) tissue characterization to detect thin-cap fibroatheroma (TCFA) identified on optical coherence tomography (OCT) has not yet been fully elucidated. METHODS AND RESULTS: We evaluated 86 coronary lesions from 73 patients with stable angina pectoris using iMap-IVUS and OCT. We defined OCT-derived TCFA (OCT-TCFA) as lipid-rich plaque with a <65-µm-thick fibrous cap. The external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured on gray-scale IVUS. Plaque components categorized on iMap-IVUS as fibrotic, lipidic, necrotic or calcified are presented as absolute area and proportion (%) of total plaque area. OCT-TCFA (22 lesions) had significantly greater EEM CSA, P+M CSA, plaque burden and remodeling index than non-TCFA (64 lesions). Significantly larger %necrotic area, absolute lipidic and necrotic areas and smaller %fibrotic areas were found in OCT-TCFA than in non-TCFA. On multivariate analysis, absolute necrotic area was an independent predictor of OCT-TCFA. The area under the ROC curve for absolute necrotic area required to identify OCT-TCFA was 0.86. The sensitivity, specificity, positive and negative predictive values of absolute necrotic area ≥7.3 mm2 for identifying OCT-TCFA were 77%, 88%, 68% and 92%, respectively. CONCLUSIONS: Coronary lesions with greater iMap-IVUS absolute necrotic area were closely associated with OCT-TCFA.

Spontaneous spiral dissection of left internal thoracic artery graft.

The left internal thoracic artery (LITA) is considered the most reliable coronary artery bypass grafting conduit due to its high rate of long-term patency. LITA grafts are extremely durable and associated complications are infrequent. We present a case with spontaneous spiral dissection of a LITA graft to the left anterior descending artery, which was assessed by optical coherence tomography (OCT) and intravascular ultrasound (IVUS). OCT was superior in visualizing the disrupted flap, false lumen, and intramural hematoma, but it did not visualize the full extent of the vessel wall. In contrast, IVUS allowed more complete and deeper vessel visualization, and thus better appreciation of the extent of intramural hematoma. Combined use of these two modalities provides complementary details on imaging of a LITA dissection.

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension.

AIMS: Echocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. MAIN METHODS: Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). KEY FINDINGS: PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP ≥ 35mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p=0.042] and PVR ≥ 400dyn·s·cm(-5) (OR, 1.804; 95% CI 1.131-2.877; p=0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was -20.75%, based on receiver operating characteristic curve analysis. SIGNIFICANCE: PSS of the RV free wall might serve as a useful non-invasive indicator of PH.

Plasma pentraxin 3 is a more potent predictor of endothelial dysfunction than high-sensitive C-reactive protein.

An inflammatory response is a key event for endothelial dysfunction. Pentraxin 3 (PTX3) is an inflammatory protein produced at inflammation sites such as leukocytes and vascular endothelial cells. Here, we compared the relationships between endothelial function assessed by flow-mediated dilation (FMD), and the levels of plasma PTX3 and high-sensitive C-reactive protein (hsCRP), another inflammatory protein of the pentraxin family. Levels of FMD, PTX3 and hsCRP were measured twice within 6 to 8 months and retrospectively analyzed in 36 patients with coronary artery disease. We examined the associations between the values of FMD and the levels of PTX3 and hsCRP at the first measurement, and between the change ratios (second value/first value) of these parameters. Univariate linear regression analysis showed significantly negative correlations between FMD values and PTX3 and hsCRP levels at the first measurement, and significant associations with taking statins or calcium antagonists. Multivariate linear stepwise regression analysis identified PTX3 levels and taking statins and calcium antagonists as independent factors for endothelial function. The change ratio of FMD correlated more closely with that of PTX3 than of hsCRP (r = -0.446, P = 0.006 versus r = -0.330, P = 0.050). Significantly more patients with decreased FMD values had increased levels of PTX3 than those of hsCRP at the second measurement compared with the fi rst measurement. Furthermore, the ratio of patients with increased PTX3, but not increased hsCRP, was significantly reduced among those with increased, rather than decreased, FMD values. Endothelial dysfunction might be more accurately predicted by plasma PTX3 levels than by serum hsCRP levels.

Elevated levels of systemic pentraxin 3 are associated with thin-cap fibroatheroma in coronary culprit lesions: assessment by optical coherence tomography and intravascular ultrasound.

OBJECTIVES: This study sought to determine whether systemic levels of pentraxin 3 (PTX3), a novel inflammatory marker, are associated with thin-cap fibroatheroma (TCFA). BACKGROUND: Biomarkers predicting the presence of TCFA in vivo have not been established. METHODS: We evaluated 75 patients (stable angina pectoris, n = 47; acute coronary syndrome, n = 28) with de novo culprit lesions who were examined by optical coherence tomography and intravascular ultrasound. We defined TCFA as lipid-rich plaque with a fibrous cap <65 µm thick. Systemic levels of PTX3 were compared between patients with and without TCFA. RESULTS: Thirty-eight and 37 patients with and without TCFA, respectively, were identified. Levels of PTX3 were significantly higher in patients with than in those without TCFA (p < 0.001) and correlated inversely with fibrous cap thickness (r = -0.71, p = 0.001) and positively with the remodeling index (r = 0.25, p = 0.037). Multivariate logistic regression analysis showed that a higher PTX3 level was the most powerful predictor of TCFA (odds ratio: 3.26, 95% confidence interval: 1.75 to 6.05, p < 0.001). Receiver-operating characteristic curve analysis showed that >3.24 ng/ml of PTX3 could predict TCFA with 84% sensitivity and 86% specificity. CONCLUSIONS: Higher levels of systemic PTX3 are associated with TCFA. Systemic PTX3 levels comprise a useful inflammatory marker that reflects coronary plaque vulnerability.

Effects of nasal continuous positive airway pressure on the glomerular filtration rate in patients with obstructive sleep apnea syndrome.

OBJECTIVE: Previous studies have shown a possible role for obstructive sleep apnea syndrome (OSAS) in the development and/or progression of chronic kidney disease (CKD). However, the impact of treatment for OSAS on CKD has not been clarified. The aim of this study was to investigate the influence of OSAS and the short-term effects of nasal continuous positive airway pressure (CPAP) on the estimated glomerular filtration rate (eGFR). METHODS: We evaluated 38 men with OSAS diagnosed on polysomnography. The associations between the eGFR and patient characteristics, including polysomnographic parameters, were evaluated. A multivariate linear regression analysis was performed to determine the independent variables associated with eGFR. We reassessed the polysomnographic data and eGFR values after three months of CPAP treatment. RESULTS: The mean serum creatinine level was 0.83±0.10 mg/dL and the mean eGFR was 77.3±12.0 mL/min/1.73 m2. A univariate analysis revealed that an older age (p<0.001), a longer mean apnea duration (p=0.006) and BMI (p=0.022) were significantly associated with lower eGFRs. A multivariate linear regression analysis showed that the independent factors associated with lower eGFRs were older age (p<0.001) and a longer mean apnea duration (p=0.048). Three months after CPAP treatment, there were significant decreases in the serum creatinine levels (p=0.013) and increases in eGFR (p=0.014). CONCLUSION: OSAS, especially that associated with an older age and a longer mean apnea duration, may contribute to lowering eGFR values, which can be reversed by CPAP treatment.