AbstractPurposeUdenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of ...pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. MethodsIn this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. Findings: In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m ( P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m ( P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. ImplicationsUdenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.
The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) ...with leucovorin (FL) versus irinotecan/S-1 (IS).
Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation.
One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896).
IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.
Objectives The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) ...national database, as well as to provide an overview of the RA patients who are currently registered in KORONA. Methods The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. Results A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010. Conclusions KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable “real-world” information for Korean RA patients.
The prognostic value of whole vessel plaque quantification has not been fully understood.
We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed ...tomography angiography.
In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area <4 mm2, plaque burden ≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume ≥306.5 mm3, fibrofatty and necrotic core volume ≥4.46 mm3, or percent total atheroma volume ≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models.
Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P < 0.001) in predicting FFR ≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95% CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P < 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not.
Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163)
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Automatic quantification of real-time three-dimensional (3D) full-volume color Doppler transthoracic echocardiography (FVCD) has been proposed as a feasible and accurate method for quantifying MR. We ...aimed to explore the clinical implications of real-time 3D-FVCD for mitral regurgitation (MR) with various clinical manifestations, in comparison with the conventional two-dimensional (2D) proximal isovelocity surface area (PISA) and volumetric method and cardiac magnetic resonance imaging (CMR) methods.
A total 186 patients with MR were enrolled prospectively. Based on exclusion criteria and image quality review, 152 patients were included in the final analysis for 3D-FVCD and 2D transthoracic echocardiography. Among them, 37 patients underwent subsequent CMR for the validation of 3D-FVCD.
MR volume from 3D-FVCD demonstrated a better agreement (r = 0.94) with CMR than 2D-PISA or the 2D volumetric method (VM; r = 0.87 vs 0.56). Overall, 2D methods underestimated MR when compared with 3D-FVCD (35.4 ± 28.4 mL for 2D-VM vs 43.8 ± 24.6 mL for 2D-PISA vs 64.6 ± 35.1 mL for 3D-FVCD; P < .001). In subgroup analysis, multijet MR (odds ratio OR, 6.30; 95% CI, 2.52-15.72) and dilated left ventricular end-systolic diameter ≥40 mm (OR, 2.90; 95% CI, 1.12-7.50) were predictors of significant difference in MR volume (>30 mL for primary MR and >15 mL for secondary MR) between 2D-PISA and 3D-FVCD. In identifying surgical candidates, patients with multijet MR (OR, 4.53, 95% CI, 1.99-10.35) demonstrated a higher risk of discrepancy between 2D-PISA and 3D-FVCD, which were consistent in both primary and secondary MR, respectively.
MR quantification with 3D-FVCD showed better correlation and agreement than conventional 2D methods. MR was underestimated by 2D methods, especially in multijet and dilated left ventricle. Multijet MR demonstrated higher risk of discrepancy for the identification of surgical candidate, regardless of MR etiology.
The discrepancy between planimetered mitral valve area (MVA) and mean diastolic pressure gradient (MDPG) has not been studied extensively in patients with mitral stenosis. The purpose of the present ...study was to investigate differences in characteristics and outcomes after mitral valve replacement (MVR) between low- and high-MDPG groups in patients with very severe mitral stenosis (VSMS). The hypothesis was that the low-MDPG group would have different characteristics and would be associated with poor clinical outcomes after MVR.
In total, 140 patients who underwent isolated MVR because of pure VSMS (planimetered MVA ≤ 1.0 cm(2)) were retrospectively reviewed, and follow-up echocardiography was performed for ≥12 months after MVR. Patients were divided into two groups according to preoperative MDPG (low gradient LG, <10 mm Hg; high gradient HG, ≥10 mm Hg). Strain and strain rate analysis was performed using speckle-tracking echocardiography of the left ventricle before MVR in a subgroup of 56 patients.
There were 82 patients (59%) in the LG group and 58 patients (41%) in the HG group. The LG group was older and demonstrated a higher prevalence of female gender, diabetes mellitus, and atrial fibrillation (P < .05 for all). When comparing the LG and HG groups, the left atrial volume index was larger (105.1 ± 51.9 vs 87.8 ± 42.9 mL/m(2), P < .001), and strain rate during isovolumic relaxation of the left ventricle was lower (0.17 ± 0.08 vs 0.29 ± 0.09 sec(-1), P < .001) in the LG group. After MVR, the percentage left atrial volume index reduction after MVR was significantly smaller in the LG group (-29.9 ± 15.1% vs -43.5 ± 16.4%, P < .001). Persistent symptoms after MVR were more common in the LG group compared with the HG group (P = .004), even though preoperative functional class was similar between the groups.
Compared with those with HG VSMS, patients with LG VSMS were older, more often female, and more frequently had diabetes mellitus and atrial fibrillation. They also had greater impairment of isovolumic relaxation, less favorable left atrial reverse remodeling, and a greater risk for persistent symptoms after MVR. These data might suggest other concurrent mechanisms for left atrial enlargement and symptom development in LG VSMS, such as atrial fibrillation and diastolic dysfunction, as well as valvular stenosis.
This study aimed to investigate the progression of mild-to-moderate aortic stenosis (AS) in patients with end-stage renal disease (ESRD) and determine its metabolic and hemodynamic contributors and ...clinical outcomes. A total of 74 patients with ESRD (50 men, age 72 ± 11 years) with mild-to-moderate AS were compared with 79 age- and gender-matched controls with normal kidney function. Clinical, laboratory, and echocardiographic features and clinical outcomes including aortic valve (AV) intervention, hospitalization due to heart failure, and cardiovascular death were analyzed. Patients with ESRD were divided into 2 subgroups according to their rate of AV area changes (group 1 n = 28, rapid progression; and group 2 n = 46, slow progression). Progression in the degree of AS was noted in 38% of patients with ESRD and 18% of controls (p <0.01) during comparable echocardiographic follow-up durations (29 ± 15 vs 27 ± 24 months, respectively, p = 0.57). In ESRD, patients in group 1 were older (p <0.01) with higher baseline log parathyroid hormone (p <0.01) and larger stroke volume (p = 0.03) than those in group 2. During clinical follow-up (48 ± 23 months), patients in group 1 showed poorer clinical outcomes than those in group 2 and controls (log-rank p <0.01). Age, left atrial volume index ≥42 ml/m2 , and annual increases of peak pressure gradient across the AV (mm Hg/year) demonstrated additive predictive values for prognosis. AS in ESRD progresses in an accelerated manner along with higher metabolic and hemodynamic loads on AV compared with those with normal kidney function. Accelerated progression of mild-to-moderate AS in ESRD results in poor prognosis.
A bicuspid aortic valve (BAV) is often associated with dilation or aneurysm of the ascending aorta (AA) despite of absence of significant valve dysfunction. Bicuspid aortopathy and consequent aortic ...stiffness may adversely affect left ventricular (LV) diastolic function. This study aimed to investigate the impact of global and regional aortic mechanical function on LV diastolic function in subjects with BAV. Fifty-six subjects with BAV (45 men, mean age 52 ± 13 years) without significant valve dysfunction and 56 age- and gender-matched controls with tricuspid aortic valve were studied. The aortic phenotypes were classified into 3 groups: normal shape, predominant dilatation of the sinus of Valsalva, and predominant dilatation of the AA. Structural and functional parameters of the AA and LV were measured using 2-dimensional echocardiography. Global aortic mechanical function was assessed by radial artery tonometry. The subjects with BAV showed a higher incidence of a predominant AA phenotype (53.6% vs 17.9%, p <0.001), larger indexed aortic diameters, increased augmentation index, lower pulse pressure amplification, lower early diastolic mitral annular (e’) velocity, and higher E/e’ than those with tricuspid aortic valve . The e’ velocity and E/e’ varied with different aortic phenotypes in subjects with BAV. Correlations between e’ velocity and parameters of aortic stiffness were stronger in subjects with BAV than those in controls. Multiple regression analysis revealed that augmentation index normalized for a heart rate of 75 beats/min was an independent determinant of e’ velocity (β = −0.24, p = 0.044) and E/e’ (β = 0.30, p = 0.018) in subjects with BAV even after controlling for confounding factors. LV diastolic function is closely related to aortic phenotype and mechanical alteration in subjects with BAV.
Background Substantial aortic calcification is known to be associated with aortic stiffening and subsequent left ventricular (LV) hypertrophy. This study examined whether the thoracic aorta calcium ...score (TACS) is related to LV hypertrophy and whether it leads to an adverse prognosis in patients with severe aortic stenosis (AS) after aortic valve replacement (AVR). Methods We retrospectively reviewed 47 patients (mean age, 64 ± 11 years) with isolated severe AS who underwent noncontrast computed tomography of the entire thoracic aorta and who received AVR. TACS was quantified using the volume method with values becoming log transformed (log TACS+1). Transthoracic echocardiography was performed before and 1 year after the operation. Results Preoperative LV mass index (LVMI) displayed significant positive correlations with male gender ( r = 0.430, p = 0.010) andlog (TACS+1) ( r = 0.556, p = 0.003). In multivariate linear regression analysis, onlylog (TACS+1) was independently associated with LVMI, even after adjusting for age, gender, transaortic mean pressure gradient, and coronary or valve calcium score. Independent determinants for postoperative LVMI includedlog (TACS+1) and preoperative LVMI after 1 year of follow-up echocardiography, adjusting for age, gender, indexed effective orifice area, and coronary or valve calcium score. During a median follow-up period of 54 months after AVR, there were 10 events (21%), which included 4 deaths from all-causes, 3 strokes, 2 inpatient admissions for heart failure, and 1 myocardial infarction. The event-free survival rate was significantly lower for patients with TACS of 2,257 mm3 or higher compared with those whose TACS was lower than 2,257 mm3 (log-rank p < 0.001). Conclusions High TACS was associated with increased LVMI among patients with severe AS. Further, high TACS usefully predicted less regression of LVMI and poor clinical outcomes after AVR. TACS may serve as a useful proxy for predicting LV remodeling and adverse prognosis in patients with severe AS undergoing AVR.
Abstract Although intraprocedural coronary computed tomographic angiography (CCTA) allows for scanning during intervention without relocation of the patient, studies have yet to report on its use ...during chronic total occlusion (CTO) intervention. Therefore, we investigated the role of CCTA during CTO intervention, particularly whether CCTA could be used to evaluate the location of guidewires. A total of 61 patients scheduled for elective CTO intervention were consecutively enrolled and underwent CCTA and on-site analyses during intervention. Transverse axial and the curved multiplanar images in a 360-degree view were interactively used together to identify the location of guidewires, along with the adjustment of window condition. Intracoronary contrast-injection was used for specific cases requiring enhancement of the distal part of the CTO. Most CCTAs were performed to confirm the location of a single guidewire; CCTA was also performed to evaluate parallel (3 patients) or retrograde wires (5 patients). The initial identification rate for guidewire location was 56% with immediate trans-axial images, but it significantly increased to 87% after interactive on-site uses of the curved multiplanar images (p <0.001). Cases in which guidewire location could be predicted with CCTA evaluation show a numerically higher success rate than those that could not (83% versus 63%), but not statistical significance ( P =0.174). The mean time for CCTA evaluation and mean radiation dose were 8.6 minutes and 2.9 mSv, respectively. No specific complications occurred after CCTA and CTO procedures. Intraprocedural CCTA for identifying the location of the guidewires is feasible and safe when used for various CTO procedural steps.
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