Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin.

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.

Healthcare utilization, medical expenditure, and mortality in Korean patients with pulmonary hypertension.

BACKGROUND: Limited data exists regarding healthcare utilization, medical expenses, and prognosis of pulmonary hypertension (PH) according to the World Health Organization (WHO) classification. We aimed to investigate mortality risk, healthcare utilization and medical expenditure in patients with PH across the five diagnostic subgroups. METHODS: We identified 2185 patients with PH, defined as peak tricuspid regurgitation velocity > 3.4 m/sec, among the consecutive patients referred for echocardiography between 2009 and 2015. Using diagnostic codes, medical records, and echocardiographic findings, the enrolled patients were classified according to the five subgroups by WHO classification. Healthcare utilization, costs, and all-cause mortality were assessed. RESULTS: Diagnostic subgroups of PH demonstrated significantly different clinical features. During a median of 32.4 months (interquartile range, 16.2-57.8), 749 patients (34.3%) died. Mortality risk was the lowest in group II (left heart disease) and highest in group III (chronic lung disease). The etiologies of pulmonary arterial hypertension (PAH) had significant influence on the mortality risk in group I, showing the worst prognosis in PAH associated with connective tissue disease. Medical expenditure and healthcare utilization were different between the PH subgroups: groups II and V had more hospitalizations and medical expenses than other groups. Regardless of PH subgroups, the severity of PH was associated with higher mortality risk, more healthcare utilization and medical expenditure. CONCLUSIONS: Significant differences in clinical features and prognostic profiles between PH subgroups reflect the differences in pathophysiology and clinical consequences. Our findings highlight the importance of comprehensive understanding of PH according to the etiology and its severity.

Risk of end-stage renal disease in patients with hypertrophic cardiomyopathy: A nationwide population-based cohort study.

Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p < 0.001). In the HCM, the incidence rate for ESRD gradually increased with age, but an initial peak and subsequent plateau in age-specific risk were observed. HCM was a significant predictor for ESRD (unadjusted HR 6.90, 95% CI 5.21-9.15, p < 0.001), as comparable to hypertension and diabetes mellitus. Furthermore, after adjusting for all variables showing the association in univariate analysis, HCM itself remained a robust predictor of ESRD development (adjusted HR 3.93, 95% CI 2.82-5.46, p < 0.001). The consistent associations between HCM and ESRD were shown in almost all subgroups other than smokers and subjects with a history of stroke. Conclusively, HCM increased the risk of ESRD, regardless of known prognosticators. It provides new insight into worsening renal function in HCM, and active surveillance for renal function should be considered.

Coronary computed tomography angiography vs. myocardial single photon emission computed tomography in patients with intermediate risk chest pain: a randomized clinical trial for cost-effectiveness comparison based on real-world cost.

AIMS: To compare the cost-effectiveness of coronary computed tomography angiography (CCTA) vs. myocardial single photon emission computed tomography (SPECT) in patients with stable intermediate risk chest pain. METHODS AND RESULTS: Non-acute patients with 10-90% pre-test probability of coronary artery disease from three high-volume centres in Korea (n = 965) were randomized 1:1 to CCTA or myocardial SPECT as the initial non-invasive imaging test. Medical costs after randomization, the downstream outcome, including all-cause death, acute coronary syndrome, cerebrovascular accident, repeat revascularization, stent thrombosis, and significant bleeding following the initial test and the quality-adjusted life-years (QALYs) gained by the EuroQoL-5D questionnaire was compared between the two groups. In all, 903 patients underwent the initially randomized study (n = 460 for CCTA, 443 for SPECT). In all, 65 patients underwent invasive coronary angiography (ICA) in the CCTA and 85 in the SPECT group, of which 4 in the CCTA and 30 in the SPECT group demonstrated no stenosis on ICA [6.2% (4/65) vs. 35.3% (30/85), P-value < 0.001]. There was no difference in the downstream clinical events. QALYs gained was higher in the SPECT group (0.938 vs. 0.955, P-value = 0.039) but below the threshold of minimal clinically important difference of 0.08. Overall cost per patient was lower in the CCTA group (USD 4514 vs. 5208, P-value = 0.043), the tendency of which was non-significantly opposite in patients with 60-90% pre-test probability (USD 5807 vs. 5659, P-value = 0.845). CONCLUSION: CCTA is associated with fewer subsequent ICA with no difference in downstream outcome. CCTA may be more cost-effective than SPECT in Korean patients with stable, intermediate risk chest pain.

Validity and reliability assessment of a peer evaluation method in team-based learning classes.

PURPOSE: Team-based learning (TBL) is increasingly employed in medical education because of its potential to promote active group learning. In TBL, learners are usually asked to assess the contributions of peers within their group to ensure accountability. The purpose of this study is to assess the validity and reliability of a peer evaluation instrument that was used in TBL classes in a single medical school. METHODS: A total of 141 students were divided into 18 groups in 11 TBL classes. The students were asked to evaluate their peers in the group based on evaluation criteria that were provided to them. We analyzed the comments that were written for the highest and lowest achievers to assess the validity of the peer evaluation instrument. The reliability of the instrument was assessed by examining the agreement among peer ratings within each group of students via intraclass correlation coefficient (ICC) analysis. RESULTS: Most of the students provided reasonable and understandable comments for the high and low achievers within their group, and most of those comments were compatible with the evaluation criteria. The average ICC of each group ranged from 0.390 to 0.863, and the overall average was 0.659. There was no significant difference in inter-rater reliability according to the number of members in the group or the timing of the evaluation within the course. CONCLUSION: The peer evaluation instrument that was used in the TBL classes was valid and reliable. Providing evaluation criteria and rules seemed to improve the validity and reliability of the instrument.

Prognostic Value of Cardiac MR Imaging for Preoperative Assessment of Patients with Severe Functional Tricuspid Regurgitation.

Purpose To explore the prognostic value of cardiac magnetic resonance (MR) imaging in predicting postoperative cardiac death in patients with severe functional tricuspid regurgitation (TR). Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all patients. Prospectively collected data included cardiac MR images, New York Heart Association (NYHA) functional class, a comprehensive laboratory test, and clinical events over the follow-up period in 75 consecutive patients (61 women and 14 men; mean age ± standard deviation, 59 years ± 9) undergoing corrective surgery for severe functional TR. Cox proportional hazards models were used to assess the association between cardiac MR parameters and outcomes. Results During a median follow-up period of 57 months (range, 21-82 months), cardiac mortality and all-cause mortality were 17.3% and 26.7%, respectively, with a surgical mortality of 6.7%. Cardiac death risk was lower with a higher right ventricular (RV) ejection fraction (EF) on cardiac MR images (hazard ratio per 5% higher EF = 0.790, P = .048). By adjusting for confounding variables, RV EF remained a significant predictor for cardiac death (P < .05) and major postoperative cardiac events (P < .05). The area under the receiver operating characteristic curve (AUC) confirmed the incremental role of RV EF on cardiac MR images in the prediction of postoperative cardiac death (AUC, 0.681-0.771; P = .041) and major postoperative cardiac events (AUC, 0.660-0.745; P = .044) on top of NYHA class. RV end-systolic volume index was also independently associated with these outcomes but failed to increase the AUC significantly. Conclusion Preoperative assessment of cardiac MR imaging-based RV EF provides independent and incremental prognostic information in patients undergoing corrective surgery for severe functional TR. (©) RSNA, 2016 Online supplemental material is available for this article.