Evaluation of balloon pulmonary angioplasty using lung perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: The aim of this study was to evaluate the effect of balloon pulmonary angioplasty (BPA) using lung perfusion single-photon emission computed tomography (SPECT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: 20 consecutive patients (64 ± 15 years) who were diagnosed with CTEPH and underwent BPA were included in this study. All patients underwent lung perfusion SPECT before and after BPA. The relationship between functional %volume of the lung calculated from the lung perfusion SPECT (FVL-LPSPECT), and other clinical parameters before and after BPA was assessed using the Wilcoxon signed-rank test. The correlation between each parameter and mean pulmonary artery pressure (mPAP) using the Spearman's correlation was performed. To determine predictors of mPAP for evaluating treatment effectiveness, significant parameters were included in multiple regression analysis. After BPA, world health organization functional classification, six-minute walk distance (6MWD), mPAP, and FVL-LPSPECT significantly improved. FVL-LPSPECT (r = - 0.728, P < 0.001) and 6MWD (r = - 0.571, P = 0.009) were significant correlation of mPAP. In the multiple regression analysis, FVL-LPSPECT was the most significant predictor of improvement in mPAP after BPA (P < 0.001). CONCLUSIONS: This study demonstrated that the lung perfusion SPECT could be a potential measurement of the effectiveness of BPA in patients with CTEPH.

Association between coronary artery calcium score on non-contrast chest computed tomography and all-cause mortality among patients with congestive heart failure.

Coronary artery calcium (CAC) score is a robust prognostic tool to predict cardiac events. Although patients with congestive heart failure (CHF) occasionally undergo non-contrast computed tomography (NCCT), the prognostic utility of CAC by NCCT is not widely known. We aimed to determine if CAC measured on NCCT is associated with all-cause mortality (ACM) among patients with CHF. We identified 550 patients admitted due to CHF who underwent NCCT. Patients were categorized into three groups according to CAC scores 0, 1-999, and ≥ 1000. The multivariate Cox proportional hazards model was used to assess if CAC by NCCT was associated with ACM after adjusting for traditional coronary artery disease (CAD) risk factors, brain natriuretic peptide and left ventricular ejection fraction (LVEF). In a subset of 245 patients with invasive coronary angiography (ICA), the associations between CAC scores and ACM were assessed in the multivariate Cox proportional hazards model. Further, we assessed if CAC increased statin use at discharge. During a mean follow-up of 3.3 ± 3.1 years, ACM occurred in 168 patients (30.55%). Compared with patients with CAC 0, those with CAC ≥ 1000 (HR 1.564, 95% CI 0.969-2.524, P = 0.067) were more likely to experience ACM, while those with CAC score 1-999 (HR 0.971, 95% CI 0.673-1.399, P = 0.873) were not. Similarly, a trend toward significance was observed in patients with LVEF < 40% (HR 2.124, 95% CI 0.929-4.856, P = 0.074). In the sub-analysis, patients with CAC ≥ 1000 had increased ACM compared to those with CAC 0, only if ICA ≥ 50% (HR 3.668, 95% CI 1.141-11.797, P = 0.029). Multivariate logistic regression revealed that statin use at discharge was increased with ICA ≥ 50%, but not CAC. The CAC score measured by NCCT tended to be associated with ACM among CHF patients. Statin use was not increased by CAC on NCCT.

α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression.

α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis.

Prognostic values of 123I-MIBG myocardial scintigraphy and heart rate variability in patients with heart failure with preserved ejection fraction.

BACKGROUND: The aim of this study was to evaluate the prognostic values of sympathetic nerve system using 123I-MIBG myocardial scintigraphy and using Holter electrocardiogram (ECG) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Among 403 consecutive patients with stable HF who underwent 123I-MIBG myocardial scintigraphy and Holter ECG, we identified 133 patients (64 ± 16 years) who had preserved ejection fraction (≥ 50%) by echocardiography. Multivariate Cox model was used to assess if washout rate (WR) by 123I-MIBG scintigraphy and very low frequency power (VLFP) by Holter ECG was associated with major adverse cardiovascular events (MACE). During a mean follow-up of 5.4 ± 4.1 years, 39 MACE occurred. The lower nighttime VLFP (HR 3.29, 95% CI 1.56 to 6.92) and higher WR (HR 4.01, 95% CI 1.63 to 9.88) were the significant prognostic factors for MACE. As compared to high nighttime VLFP and low WR group, MACE risk was significantly the highest in the low nighttime VLFP and high WR group (HR 40.832; 95% CI 5.378 to 310.012, P < 0.001). CONCLUSION: This study demonstrated that the nighttime VLFP adding to WR could be a potential prognostic value among patients with HFpEF.

Relationship Between 18F-fluorodeoxyglucose Uptake on Positron Emission Tomography and Aortic Calcification.

Introduction: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been widely utilized to assess the extent of inflammation, the association between the extent and severity of atherosclerosis and 18F-FDG uptake on PET remains unexamined. The current study aimed to investigate whether aortic calcium (AC) scores were associated with increased aortic uptake of 18F-FDG on PET. Methods: A total of 167 consecutive patients with suspected lung cancer but unproven malignancy who underwent non-contrast-enhanced computed tomography (CT) and 18F-FDG PET/CT were enrolled. The average standardized uptake values in the ascending aorta were used to calculate the target-to-background ratio (Mean TBR). The total (thoracic and abdominal) AC scores were measured on non-contrast-enhanced chest and abdominal CT using the Agatston method, and were categorized into three groups (0, 1-399, and ≥400). The relationship between total AC scores and 18F-FDG uptake in the ascending aorta was assessed using multivariate linear regression analysis. Results: In total, 68.26% were male, and a mean age was 67.10±14.70 years. Mean TBR values increased progressively with total AC score 0, 1-399, and ≥400 (1.01±0.07, 1.08±0.09, and 1.11±0.11, respectively; p<0.00001). Multivariate linear regression analysis revealed that increased total AC scores of 1-399 (ß=0.06, 95% CI: 0.01-0.11, p=0.02) and ≥400 (ß=0.11, 95% CI: 0.06-0.16, p<0.001) were significantly associated with higher Mean TBR. Conclusions: The current study demonstrated that total AC scores were associated with Mean TBR. Patients with a greater extent and severity of aortic calcifications may possess increased atherosclerotic inflammatory activity as measured by 18F-FDG PET/CT.

Prognostic values of coronary artery calcium score and 123I-BMIPP SPECT in patients with non-ischemic heart failure with preserved ejection fraction.

This study aimed to determine whether coronary artery calcium score (CACS) can be a prognostic indicator for the development of major adverse cardiac events (MACEs) and compare the value of CACS with that of the 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) defect score (BDS) in patients with non-ischemic heart failure with preserved ejection fraction (NIHFpEF). Among 643 consecutive patients hospitalized due to acute heart failure, 108 (74 ± 13y) were identified to have NIHFpEF on non-contrast regular chest computed tomography and 123I-BMIPP single-photon emission computed tomography (SPECT). We evaluated whether CACS and BDS were associated with MACEs using multivariate Cox models. Thirty-two MACEs developed at a mean follow-up period of 2.4 years. CACS > 0 (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.02-5.54) and higher BDS (HR 16.00, 95% CI 5.88-43.49) were significantly associated with the development of MACEs. The proportion of patients who experienced MACEs was significantly higher in the CACS > 0 and high BDS group than in the CACS = 0 and low BDS group (3% vs. 75%, p < 0.001). CACS, as well as BDS, could serve as potential prognostic indicators in patients with NIHFpEF.

Prognostic value of 99mTc-ECD brain perfusion SPECT in patients with atrial fibrillation and dementia.

BACKGROUND: Patients with atrial fibrillation (AF) and dementia experience reduced quality of life and increased mortality. Technetium 99m ECD brain perfusion single-photon emission computed tomography (99mTc-ECD brain perfusion SPECT) is a beneficial modality for diagnosing dementia and identifying high-risk patients with mild cognitive impairment. The aim of this study was to evaluate the prognostic value of brain perfusion using 99mTc-ECD SPECT in patients with AF and dementia. METHODS: Of a total of 405 consecutive patients diagnosed with AF as cardiac outpatients with dementia using the Mini-Mental State Examination by neurologists or psychiatrists, we identified 170 patients (81 ± 10 years) who underwent 99mTc-ECD brain perfusion SPECT. Of them, 73, 73, and 24 were diagnosed with Alzheimer's dementia (AD), vascular dementia (VD), and non-specified dementia, respectively. A multivariable Cox model was used to assess if higher Z-score by 99mTc-ECD brain perfusion SPECT and clinical parameters were associated with major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, hospitalization for heart failure, and stroke. RESULTS: During a mean follow-up of 1258 ± 1044 days, 62 MACE occurred. There was no significant difference in MACE between AD and VD (33%, vs. 44%, p = 0.153). The multivariable Cox model confirmed that the higher Z-score of temporo-parieto-occipital lobe was associated with increased MACE compared to the lower group (HR 2.521, 95% CI 1.465-4.337, p < 0.001). CONCLUSION: This study demonstrated that decreased cerebral blood flow in the temporo-parieto-occipital lobe could be a potential prognostic value in patients with both AF and dementia.

The relationship between coronary artery calcium density and optical coherence tomography-derived plaque characteristics.

BACKGROUND AND AIMS: Although coronary artery calcium (CAC) density has been associated with plaque stability, pathological evidence is lacking. We investigated the relationship between coronary computed tomography (CCT)-derived CAC density and multiple calcified and high-risk plaque (HRP) characteristics using optical coherence tomography (OCT). METHODS: We analyzed 83 plaques from 33 stable angina patients who underwent both CCT and OCT. CAC density was measured at calcium plaques with ≥90 Hounsfield units (HU) and ≥130 HU using custom CT software. The correlation between median CAC density and OCT-derived calcium size (thickness and area) was assessed. To investigate whether median CAC densities measured at the 90 HU threshold were associated with plaque vulnerability, OCT-derived plaque characteristics and HRP characteristics were compared between the low (90-129 HU), intermediate (130-199 HU) and high (≥200 HU) CAC HU groups. RESULTS: Median CAC densities at 130 HU were moderately associated with calcium thickness (R = 0.573, p < 0.001) and area (R = 0.560, p < 0.001). Similar results were observed at 90 HU (thickness, R = 0.615, p < 0.001; area, R = 0.612, p < 0.001). Among groups with low, intermediate and high HU levels, calcium thickness (0.42 ± 0.14 mm, 0.60 ± 0.17 mm and 0.77 ± 0.19 mm, respectively; p < 0.001) and area (0.55 ± 0.29 mm2, 1.20 ± 0.58 mm2 and 1.78 ± 0.87 mm2, respectively; p < 0.001) were significantly greater in the high HU group. HRP characteristics, however, did not differ among the three groups. CONCLUSIONS: OCT-derived calcium size, but not HRP characteristics, were associated with CAC density, suggesting that CAC density is driven mainly by calcified plaque size but not local plaque vulnerability.

Prognostic Value of 123I-BMIPP SPECT in Patients with Nonischemic Heart Failure with Preserved Ejection Fraction.

Imaging of myocardial fatty acid metabolism using 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) SPECT is useful for identifying high-risk patients with known ischemic heart disease. However, its utility for patients who have nonischemic heart failure with preserved ejection fraction is not well known. This study aimed to evaluate the prognostic value of the 123I-BMIPP defect score in such patients. Methods: Of 804 consecutive patients who were admitted to the hospital because of acute heart failure and underwent 123I-BMIPP SPECT, we identified 133 (mean age ± SD, 73 ± 13 y) who had normal coronary arteries by invasive coronary angiography and preserved left ventricular ejection fraction (≥50%) by echocardiography. 123I-BMIPP defects were quantitatively scored to obtain summed defect scores in 17 segments of 123I-BMIPP SPECT images. The patients were divided into 2 groups based on their score. The multivariate Cox model was used to assess a possible correlation between a higher score (≥4, n = 46) and major adverse cardiac events, including cardiac death, cardiovascular events, and hospitalization for heart failure, compared with a lower score (<4, n = 87). Results: During a mean follow-up of 2.5 y, 35 major adverse cardiac events occurred. The median scores in the high-score and low-score groups were 7.13 ± 4.21 and 1.29 ± 0.80, respectively. By multivariate Cox analysis, a higher score was associated with increased major adverse cardiac events, compared with a lower score (hazard ratio, 11.04; 95% confidence interval, 4.93-24.74; P < 0.001). Conclusion: This study demonstrated that the defect score by 123I-BMIPP SPECT may have potential prognostic value in patients who have nonischemic heart failure with preserved ejection fraction.

Development of a novel drug delivery system consisting of an antitumor agent tocopheryl succinate.

We have developed a novel drug delivery system (DDS) using an antitumor agent, α-tocopheryl succinate (TS). TS has attracted attention as a unique anti-cancer drug for its ability to induce apoptosis in various cancer cells. Furthermore, TS itself readily forms nanovesicles (TS-NVs) and is a prospective tool for use as an antitumor DDS. However, TS-NVs are unstable for encapsulating drugs and passive targeting delivery to tumor tissue via enhanced permeation and retention effect. Therefore, to improve the stability of vesicles, we developed a novel nanovesicle consisting of TS and egg phosphatidylcholine (TS-EPC-NVs). The stability of vesicles of TS-EPC-NVs was significantly higher than that of TS-NVs. As a result, the in vivo antitumor activity of TS-EPC-NVs was more potent than that of TS-NVs. The enhanced antitumor activity of TS-EPC-NVs was found to be due to its effective intratumoral distribution. Moreover, the in vitro anticancer efficiency of TS-EPC-NVs increased seven-fold. We suggest that the improvement is due to homogenous cellular uptake and enhanced cytosolic delivery of the nanovesicles via alteration of intracellular trafficking. Furthermore, TS-EPC-NVs encapsulating siRNA showed significant knockdown efficiency. In summary, TS-EPC-NVs represent a novel and attractive drug delivery system. The system shows antitumor activity of the encapsulated drug and the carrier itself.

Terapêutica em obesidade: atualizaçäo / Therapy of obesity: actualization

Os autores abordam o tratamento da obesidade mencionando, inicialmente, mecanismos fisiopatológicos hoje melhor conhecidos. Traçam linhas gerais do esquem dietético e citam a importância dos exercícios como fator de lipólise. No que diz respeito aos inibidores do apetite os autores realizam revisäo bibliográfica dos medicamentos disponíveis abordando aspectos práticos da prescriçäo destes fármacos. Criticam também o receituário de outros medicamentos indicando os casos específicos de sua utilizaçäo. Quanto aos tratamentos näo medicamentosos säo mencionados vantagens e inconvenientes do jejum e da cirurgia. Finalizando os autores chamam a atençäo para a importância da modificaçäo comportamental como peça básica na manutençäo do peso perdido