AT2 receptor stimulation inhibits phosphate-induced vascular calcification.

Vascular calcification is a common finding in atherosclerosis and in patients with chronic kidney disease. The renin-angiotensin system plays a role in the pathogenesis of cardiovascular remodeling. Here, we examined the hypothesis that angiotensin II type 2 receptor (AT2) stimulation has inhibitory effects on phosphate-induced vascular calcification. In vivo, calcification of the thoracic aorta induced by an adenine and high-phosphate diet was markedly attenuated in smooth muscle cell-specific AT2-overexpressing mice (smAT2-Tg) compared with wild-type and AT2-knockout mice (AT2KO). Similarly, mRNA levels of relevant osteogenic and vascular smooth muscle cell marker genes were unchanged in smAT2-Tg mice, while their expression was significantly altered in wild-type mice in response to high dietary phosphate. Ex vivo, sections of thoracic aorta were cultured in media supplemented with inorganic phosphate. Aortic rings from smAT2-Tg mice showed less vascular calcification compared with those from wild-type mice. In vitro, calcium deposition induced by high-phosphate media was markedly attenuated in primary vascular smooth muscle cells derived from smAT2-Tg mice compared with the two other mouse groups. To assess the underlying mechanism, we investigated the effect of PPAR-γ, which we previously reported as one of the possible downstream effectors of AT2 stimulation. Treatment with a PPAR-γ antagonist attenuated the inhibitory effects on vascular calcification observed in smAT2-Tg mice fed an adenine and high-phosphate diet. Our results suggest that AT2 activation represents an endogenous protective pathway against vascular calcification. Its stimulation may efficiently reduce adverse cardiovascular events in patients with chronic kidney disease.

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study.

AIMS: To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target. MATERIALS AND METHODS: This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group. RESULTS: Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007). CONCLUSIONS: This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.

Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the Assessment of Myocardial Ischemia.

BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

Rural-Urban Disparity in Emergency Care for Acute Myocardial Infarction in Japan.

BACKGROUND: There are few reports examining regional differences between rural prefectures and metropolitan areas in the management of acute myocardial infarction (AMI) in Japan.Methods and Results:In the Rural AMI registry, a prospective, multi-prefectural registry of AMI in 4 rural prefectures (Ishikawa, Aomori, Ehime and Mie), a total of 1,695 consecutive AMI patients were registered in 2013. Among them, 1,313 patients who underwent primary percutaneous coronary intervention (PPCI) within 24 h of onset were enrolled in this study (Rural group), and compared with the cohort data from the Tokyo CCU Network registry for AMI in the same period (Metropolitan group, 2,075 patients). The prevalence of direct ambulance transport to PCI-capable facilities in the Rural group was significantly lower than that in the Metropolitan group (43.8% vs. 60.3%, P<0.01), which resulted in a longer onset-to-balloon time (OTB: 225 vs. 210 min, P=0.02) and lower prevalence of PPCI in a timely fashion (OTB ≤2 h: 11.5% vs. 20.7%, P<0.01) in the Rural group. Multivariate analysis revealed that direct ambulance transport was the strongest predictor for PPCI in a timely fashion (odds ratio=4.13, P<0.001). CONCLUSIONS: AMI patients in rural areas were less likely to be transported directly to PCI-capable facilities, resulting in time delay to PPCI compared with those in metropolitan areas.

Incremental value of left atrial active function measured by speckle tracking echocardiography in patients with hypertrophic cardiomyopathy.

PURPOSE: Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients. METHODS: Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole. RESULTS: Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain <20.3% than with active strain ≥20.3% (P = .01). CONCLUSION: Loss of LA active function was associated with increased cardiac events in patients with HCM.

A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy.

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Pulmonary Hypertension as a Possible Cause of Paradoxical Low-Flow, Low-Gradient Aortic Stenosis.

Paradoxical low-flow, low-gradient aortic stenosis (LFLG AS) is recognized as a subtype of aortic stenosis. A small left ventricular (LV) cavity with marked LV concentric remodeling leads to a reduced stroke volume in this condition. The case is reported of a paradoxical LFLG AS patient who was undergoing treatment for pulmonary hypertension (PH) and interstitial pneumonia associated with scleroderma. Echocardiography demonstrated enlargement of the right ventricle and a diminished LV cavity. Moreover, the aortic valve opening was restricted despite a preserved LV ejection fraction (61%). The patient's aortic valve area (obtained with the continuity equation) was 0.57 cm2 (indexed AVA was 0.39 cm2/m2), and the mean gradient was 16 mmHg. Multi-detector computed tomography findings confirmed that the aortic valve calcification was not severe. The main mechanism responsible for LFLG AS was considered to be a reduced LV cavity secondary to PH, rather than a sclerotic aortic valve. Thus, a decision was taken to treat the patient with additional medical management prior to performing any invasive procedures. It should be borne in mind that PH can lead to paradoxical LFLG AS, and that appropriate treatment should be contemplated depending on the underlying mechanisms. Video 1: Transthoracic echocardiography in the parasternal long-axis view showing right ventricular dilatation and a diminished left ventricular cavity. Video 2: Transthoracic echocardiography in the shortaxis view showing enlargement of the right ventricle and septal flattening due to pulmonary hypertension. Video 3: Transesophageal echocardiography clearly demonstrates an insufficient valve opening.

Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury.

Clinical Significance of Peripheral Endothelial Function for Left Atrial Blood Stagnation in Nonvalvular Atrial Fibrillation Patients With Low-to-Intermediate Stroke Risk.

BACKGROUND: In patients who have atrial fibrillation (AF) with CHADS2score of 0-1 (categorized as low-to-intermediate risk), there is little information on stratifying the risk of stroke. This study aimed to determine whether impaired endothelial function assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) predicted left atrial blood stagnation in these patients. METHODS AND RESULTS: We enrolled 81 consecutive patients with nonvalvular AF. The reactive hyperemia index (RHI) was measured using RH-PAT. Transesophageal echocardiography was performed to determine spontaneous echo contrast (SEC) before direct-current cardioversion or radiofrequency catheter ablation. SEC was found in 49 patients (60%). The RHI was significantly lower in patients with than without SEC. Multivariate analysis demonstrated that RHI was one of the independent determinants of SEC (OR per 0.1, 1.26; 95% CI, 1.11-1.49; P=0.002) in all patients. In addition, RHI was a significant determinant of SEC (AUC, 0.73; 95% CI, 0.63-0.89; P=0.0017) in patients with low-to-intermediate risk. At an RHI cut-off <1.62, the sensitivity and specificity for the identification of patients with SEC were 58% and 89%, respectively. CONCLUSIONS: Impaired endothelial function assessed by RH-PAT might help to predict the presence of SEC in patients with low-to-intermediate risk of stroke. (Circ J 2016; 80: 2117-2123).

Clinical Utility of Atrial Electromechanical Conduction Time Measured with Speckle Tracking Echocardiography after Catheter Ablation in Patients with Atrial Fibrillation: A Validation Study with Electroanatomical Mapping.

PURPOSE: Our recent report demonstrated that atrial electromechanical conduction time (EMT-ε) measured with speckle tracking echocardiography could predict cardiac events in patients with pathological left ventricular hypertrophy. This study aimed to validate EMT-ε by comparison with electroanatomical mapping and to investigate the clinical utility of EMT-ε in patients with atrial fibrillation (AF) undergoing catheter ablation. METHODS: Forty-six patients with preserved LV ejection fraction (LVEF ≥ 50%) undergoing pulmonary vein isolation (PVI) for AF were studied. Atrial electrical conduction delay was determined by measuring atrial electrical activation time (EAT) using three-dimensional electroanatomical mapping just after PVI. Echocardiographic parameters were acquired within 24 hours and at 6 months after PVI. The study also included 10 control subjects. RESULTS: AF patients had a larger left atrial (LA) volume index (LAVI) and more prolonged EMT-ε compared with control subjects. According to the validation study, EAT was closely related to EMT-ε and a', and this association was independent of LAVI and the presence of persistent AF (EMT-ε: R(2) = 0.342, P < 0.0001, a': R(2) = 0.337, P < 0.0001). At 6 months after PVI, LAVI and EMT-ε were significantly improved. During continued follow-up beyond 6 months (total follow-up, 26 ± 12 months), the EMT-ε shortening at 6 months after PVI was significantly greater in AF-free patients than patients with AF recurrence. CONCLUSIONS: This study suggested that the EMT-ε could be a useful echocardiographic marker of LA electromechanical abnormalities in patients with AF.

The Importance of Walking for Control of Blood Pressure: Proof Using a Telemedicine System.

BACKGROUND: Regular physical activity (PA), including daily walking, reduces the risk of many chronic diseases, especially hypertension. Pedometer is a potential motivational aid for increasing PA. In the present study, we used a telemedicine system and analyzed the relationship between daily walking, calculated by pedometers, and blood pressure (BP). METHODS: BP was measured at home twice a day (morning and evening) using an oscillometric automatic device. Body weight (BW) and percent body fat (%BF) were measured after BP measurement. Daily walking steps (DWS) were calculated by a pedometer. These daily parameters were transmitted through the Internet to a central server computer and sent to the Medical Health Center. RESULTS: Sixty-nine (N = 69) hypertensive patients were included in this study. The mean follow-up period was 378 days. Electronic data from a pedometer (DWS) were associated with reduced BW, body mass index, and %BF. Hypertensive patients were divided into two groups based on the DWS. In the high DWS group, morning systolic BP and diastolic BP and evening systolic BP were reduced after induction of the telemedicine system. CONCLUSION: A telemedicine system confirmed the usefulness of walking to control BP in hypertensive patients.

Compensatory increase of left atrial external work to left ventricular dysfunction caused by afterload increase.

Afterload mismatch can cause acute decompensation leading to an occurrence of acute heart failure. We investigated how the left atrium (LA) and left ventricle (LV) react to acute increases in afterload using speckle tracking echocardiography (STE). LA strain and volume were obtained by STE in 10 dogs during banding of descending aorta (AoB). Simultaneously, LA pressure was measured by a micromanometer-tipped catheter. LA peak negative strain during LA contraction, strain change during LA relaxation (early reservoir strain), and that during LA dilatation (late reservoir strain) were obtained from LA longitudinal strain-volume curves. From pressure-strain curves, the areas of A-loop and V-loops were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work). AoB increased LV systolic pressure (105 ± 15 vs. 163 ± 12 mmHg, P < 0.01) and mean LA pressure (3.8 ± 1.2 vs. 7.1 ± 2.0 mmHg, P < 0.01). LV global circumferential strain decreased (-18.8 ± 3.5 vs. -13.2 ± 3.5%, P < 0.01), but LV stroke volume was maintained (8.4 ± 2.3 vs. 9.6 ± 3.6 ml). LA peak negative strain (-2.9 ± 2.3 vs. -9.8 ± 4.0%, P < 0.01) and early reservoir strain (4.5 ± 2.1 vs. 7.7 ± 2.4%, P < 0.05) increased by AoB, but late reservoir strain did not change (8.9 ± 3.4 vs. 6.1 ± 3.4%). A-work significantly increased (3.2 ± 2.0 vs. 19.2 ± 15.1 mmHg %, P < 0.01), whereas V-work did not change (13.3 ± 7.1 vs. 13.1 ± 7.7 mmHg %). In conclusion, LA external work during active contraction and relaxation increased as compensation for LV dysfunction during aortic banding. Atrial dysfunction may lead failure of this mechanism and hemodynamic decompensation.

Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle Tracking Echocardiography.

BACKGROUND: The pathological process of left ventricular (LV) hypertrophy is associated with left atrial (LA) remodeling. This study was aimed to evaluate the prognostic value of LA strain parameters in patients with pathological LV hypertrophy. METHODS: This study included 95 patients with hypertensive heart disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac amyloidosis (CA: n = 15), and control subjects (n = 20). We used two-dimensional speckle tracking echocardiography (STE) to analyze LA global strain. LA electromechanical conduction time (EMT) at the septal (EMT-septal) and lateral wall (EMT-lateral), and their time difference (EMT-diff) were calculated. The incidence of cardiac death and heart failure hospitalization was defined as major cardiac events and that of atrial fibrillation as secondary outcome. RESULTS: Left atrial volume index was increased and LA booster strain was decreased in the HCM and CA groups compared with the HHD group. EMT-lateral was increased in the diseased groups compared with the control. EMT-diff was prolonged in the CA group compared with the HCM group. During the follow-up period (mean 3.4 years), major cardiac events and atrial fibrillation occurred in 17 and 13 patients, respectively. The occurrence of atrial fibrillation was associated with CA etiology, E/e', LA volume index, LAa, and EMT-lateral. The incidence of major cardiac events was independently correlated with LA volume index and EMT-diff in multivariate analysis. CONCLUSION: This study suggested that the EMT-diff could discriminate patients with a high risk of cardiac events among patients with pathological LV hypertrophy.

Carotid hemodynamics is associated with monocyte count determined by serum homocysteine level in patients with essential hypertension.

To examine the association between pulsatility index (PI) in the common carotid artery (CCA) as a marker of vascular resistance and cardiovascular risk factors, including serum homocysteine and inflammation, 67 hypertensive patients were enrolled. PI correlated with homocysteine and interleukin-6, monocyte count, gender, age and BMI, with monocyte count and age being independent determinants for PI. In turn, monocyte count correlated with homocysteine, tumor necrosis factor-alpha, and HDL-cholesterol, BMI, and gender, with HDL-cholesterol and homocysteine being independent determinants for monocyte count. These results indicated monocyte count determined by homocysteine is associated with arterial stiffness in hypertensive patients.

Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy.

Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients.

Positron emission tomography-computed tomography for imaging of inflammatory cardiovascular diseases.

Inflammation is a determinant of atherosclerotic plaque rupture, the event usually responsible for myocardial infarction and stroke. Possible causes of inflammatory cardiomyopathy include myocarditis, eosinophilic disease, and sarcoidosis. Although conventional imaging techniques can identify the site and severity of luminal stenosis, they do not provide information regarding inflammatory status. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for imaging of inflammatory cardiovascular diseases has been rapidly evolving. Integrated PET/computed tomography (CT) is becoming the method of choice for quantification of arterial inflammation across multiple vessels. Moreover, PET/CT provides information about the activation status of inflammatory cells in the vessel wall, thus allowing early diagnosis and risk stratification of patients. The Japanese health insurance system approved reimbursement for FDG-PET use to detect inflammation sites in cardiac sarcoidosis as of April 2012. This approval has necessitated a more detailed assessment of the clinical value of FDG-PET. Standardized preparation, imaging, and image interpretation protocols should be established to sufficiently suppress physiological FDG uptake in the normal myocardium, and thereby facilitate detection of early-stage cardiac inflammatory lesions with more favorable specificity. This review summarizes the background, clinical utility, state-of-the-art advances, and potential future applications of FDG-PET for imaging inflammatory cardiovascular diseases including cardiac sarcoidosis, large-vessel arteritis, and atherosclerosis.

Combined supine and prone myocardial perfusion single-photon emission computed tomography with a cadmium zinc telluride camera for detection of coronary artery disease.

BACKGROUND: Myocardial perfusion SPECT (MPS) traditionally requires the patient to be in the supine position, but diaphragmatic attenuation of the inferior wall reduces test specificity. The aim of this study was to assess the feasibility of combined MPS in the supine and prone positions using a novel cadmium zinc telluride (CZT) camera. METHODS AND RESULTS: A total of 276 consecutive patients with suspected/known coronary artery disease (CAD) who underwent single-day (99m)Tc-tetrofosmin or (99m)Tc-sestamibi stress/rest CZT SPECT, were enrolled in the study. Seventy-six underwent coronary angiography. Five-minute scan in the supine (S) position and thereafter in the prone (P) position produced images that were visually interpreted to obtain summed stress (SSS) and rest (SRS) scores. A combined stress score (C-SSS) was calculated by grouping anterior perfusion defects observed during supine imaging with inferior half segments observed during prone imaging. The SSS for the supine, prone, and combined protocols were 9±8, 7±8, and 7±8, respectively (P<0.0001). The SRS were 5±8, 4±7, and 6±7, respectively (P=0.005). The area under the ROC curve for the S-SSS, P-SSS, and C-SSS scores was 0.815 (95% CI: 0.713-0.917), 0.813 (0.711-0.914), and 0.872 (0.783-0.961), respectively. Corresponding sensitivities and specificities for detecting CAD were 87% and 50%, 80% and 77%, and 85% and 82%, respectively. C-SSS had significantly better specificity and accuracy than S-SSS (P<0.05). CONCLUSIONS: Combined imaging with a CZT camera is suitable for routine clinical MPS and provides greater diagnostic accuracy than supine imaging alone.

Phase II trial of S-1 as third-line or further chemotherapy in patients with advanced non-small-cell lung cancer.

OBJECTIVES: This study was conducted to evaluate the efficacy and safety of S-1 in patients with advanced non-small-cell lung cancer (NSCLC), receiving two or more prior chemotherapy regimens. METHODS: S-1 was administered orally for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity occurred. RESULTS: From 2010 to 2012, 45 patients were enrolled in this study. Of the 45 patients, 4 patients [8.9 %, 95 % confidence interval (CI) 0.6-17.2 %] exhibited a partial response and 24 patients (53.3 %) exhibited stable disease. The disease control rate was 62.2 % (95 % CI 48.1-76.4 %). Median progression-free survival was 71 days, and median survival time was 205 days. Four patients had grade 3 hematological toxicities, but toxicities of grade 4 were not observed in this study. CONCLUSION: Although S-1 monotherapy as third-line treatment or beyond was well tolerated, the response rate for this regimen did not demonstrate sufficient activity for patients with advanced NSCLC.