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.

Effect of Infarction-Related Artery Location on Clinical Outcome of Patients With Acute Myocardial Infarction in the Contemporary Era of Percutaneous Coronary Intervention　- Subanalysis From the Prospective Japan Acute Myocardial Infarction Registry (JAMIR).

BACKGROUND: Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents.Methods and Results:This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis. CONCLUSIONS: The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.

A case of chronic myocarditis.

Chronic myocarditis is sometimes difficult to diagnose using several clinical diagnostic modalities. A 43-year-old Japanese man was admitted to our hospital with heart failure due to a diffusely hypokinetic left ventricle. No abnormal accumulation was seen on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Coronary angiography showed no abnormalities. Endomyocardial biopsy was performed on suspicion of dilated cardiomyopathy, revealing diffuse cell infiltration (more T lymphocytes associated with macrophages than B cells on immunohistochemical staining), myocyte damage, and replacement fibrosis. The pathological diagnosis of biopsy specimen was difficult to differentiate between chronic myocarditis and inflammatory dilated cardiomyopathy without immunohistochemistry. Endomyocardial biopsy offers one of the most useful methods for diagnosing chronic myocarditis.

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.

Effectiveness and safety of oral direct factor Xa inhibitors for the treatment of venous thromboembolism in patients with cancer and/or older age.

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients' demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p < 0.001). The efficacy and safety of Xa inhibitors as VTE treatment were comparable between cancer and non-cancer patients, and in elderly and non-elderly patients. This suggests that Xa inhibitors may be promising drugs for VTE treatment, irrespective of age and comorbid cancer.

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.

Lower Circulating Omega-3 Polyunsaturated Fatty Acids Are Associated with Coronary Microvascular Dysfunction Evaluated by Hyperemic Microvascular Resistance in Patients with Stable Coronary Artery Disease.

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD).Intracoronary physiological variables (fractional flow reserve (FFR), hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (ß = -0.31, P = 0.001) and EPA (ß = -0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (ß = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (ß = -0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (ß = 0.26, P = 0.008) but not with Pd at hyperemia.A lower serum EPA/AA ratio may cause CMD in patients with stable CAD.

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.

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.

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.

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC.

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.

Association between apolipoprotein C-III levels and coronary calcification detected by intravascular ultrasound in patients who underwent percutaneous coronary intervention.

There are few reports on the association between apolipoprotein C-III (ApoC-III) and coronary calcification using intravascular modalities. This study aimed to investigate the impacts of ApoC-III levels on coronary calcification using grayscale intravascular ultrasound (IVUS). Consecutive 263 culprit lesions for 202 patients who underwent percutaneous coronary intervention using grayscale IVUS were included in this study and divided into four groups based on quartile ApoC-III values. This study assessed plaque characteristics, including severe calcification (>180° arc) at the minimum lumen area site and presence of calcified nodules within the culprit lesion using grayscale IVUS, and evaluated whether ApoC-III levels were associated with coronary calcified plaques. The highest ApoC-III quartile [Quartile 4 (Q4)] had a higher proportion of complex lesions, calcified plaques, severe calcification, calcified nodules, plaque burden, and total atheroma volume than the lowest ApoC-III quartile [Quartile 1 (Q1)]. Additionally, multivariable logistic regression analysis showed that Q4 was significantly associated with severe calcification and calcified nodules, with Q1 as the reference (odds ratio [OR]: 2.70, 95% confidence intervals [CIs]: 1.04-7.00, p = 0.042; and OR: 3.72, 95% CIs 1.26-11.0, p = 0.017, respectively). Furthermore, ApoC-III level (1-mg/dl increase) was a strong significant predictor of severe calcification (OR: 1.07, 95% CIs: 1.00-1.15, p = 0.040) and calcified nodules (OR: 1.09, 95% CIs: 1.01-1.19, p = 0.034) according to the multivariable logistic regression analysis. This study is the first to verify that elevated ApoC-III levels are associated with the development of severe calcification and progression to calcified nodules as detected by grayscale IVUS.

Serial Optical Coherence Tomography Assessment of Coronary Atherosclerosis and Long-Term Clinical Outcomes.

BACKGROUND: The impact of high-risk coronary artery plaques identified using optical coherence tomography on late luminal narrowing and clinical events remains poorly understood. METHODS AND RESULTS: This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention and serial optical coherence tomography at baseline and 1-year follow-up to investigate nontarget regions with angiographically intermediate stenosis. At 1 year after percutaneous coronary intervention, the coronary artery lumen area decreased significantly from 6.06 (95% CI, 5.60-6.53) mm2 to 5.88 (95% CI, 5.41-6.35) mm2 (difference, -0.18; 95% CI, -0.22 to -0.14 mm2; P<0.001), particularly in thin-cap fibroatheromas, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. The prevalence of fibroatheroma decreased from 38% to 36% (P<0.001), whereas calcified plaque increased from 31% to 34% (P<0.001), accompanied by a significant increase in calcium thickness and angle. Diabetes and current smoking habits were independently associated with increasing calcium prevalence. Patients with thin-cap fibroatheroma had a significantly higher 3-year risk of ischemia-driven nontarget vessel revascularization (hazard ratio, 2.42 [95% CI, 1.03-5.71]; P=0.04), primarily due to revascularization in the imaged region. No significant association was observed between coronary artery calcium prevalence and clinical outcomes within 3 years. CONCLUSIONS: The coronary artery lumen area significantly decreased over a 1-year interval, particularly in thin-cap fibroatheromas, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. Although thin-cap fibroatheroma prevalence was associated with higher risk of ischemia-driven nontarget vessel revascularization, no significant association was noted between coronary artery calcium prevalence and clinical outcomes within 3 years. The interaction between calcium progression and long-term clinical events necessitates further investigation. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique Identifier: UMIN000031937.

Chronic renal artery dissection with aneurysm formation treated by stent implantation with coil embolization with detailed intravascular ultrasound evaluation.

Treatment options for chronic renal artery dissection, which is a rare cause of renal artery stenosis and renovascular hypertension, such as medical management, percutaneous intervention, and open surgical repair remain controversial. We describe a 55-year-old man with a chronic dissecting aneurysm of a renal artery complicated with renovascular hypertension that was initially diagnosed by computed tomography angiography, evaluated by intravascular ultrasound, and treated by stent implantation with coil embolization.© 2012 Wiley Periodicals, Inc.

Three-dimensional optical coherence tomography to decide on reverse wire technique in bifurcation interventions.

A 79-year-old male with effort angina was admitted to receive optical coherence tomography (OCT)-guided percutaneous coronary intervention for restenosis of an everolimus-eluting stent implanted to the left anterior descending artery (LAD) eight years ago.