Formation of the interatrial septum: Insights obtained from cardiac computed tomographic angiography.

We previously described a septal variant termed left atrial septal pouch (LASP). Present in a third of hearts, it results from incomplete fusion of the septum primum (SP) and septum secundum (SS). We assessed the prevalence of LASP using 64-section multidetector computed tomography and further characterized the different variants. Among 864 scans, 770 were of sufficient quality for assessment (428 male, aged 59.2 ± 11.7 years). They were classified on the basis of the degrees of fusion of the SP and SS into a completely fused septum (CFS), patent foramen ovale (PFO), or LASP. The lengths of the SS, SP, and overlapping SP, the maximal length of the foramen ovale (FO) floor, and the atrial dimensions were compared. A PFO was seen in 181 patients (23.5%), a LASP in 242 (31.4%), and a CFS in 339 (44.0%). There were significant differences in the length of the SS (PFO-13.6 ± 4.3 mm, LASP-17.6 ± 4.8 mm, CFS-14.3 ± 7.7 mm, p < 0.001). Hearts with LASPs had a longer overlapping SP than those with PFOs (PFO-6.3 ± 4.5 mm, LASP-13.1 ± 5.2 mm, p < 0.001). The maximal lengths of the FO floor showed differences in short axis (SAX) view (PFO-21.7 ± 4.5 mm, LASP-15.3 ± 4.3 mm, CFS-16.3 ± 4.3 mm, p < 0.001). Hearts with PFO and LASP showed similar SP lengths (27.3 ± 6.6 mm vs. 26.4 ± 6.6 mm, p = 0.10). There was a positive linear correlation between the length of the SS and the overlapping SP (R2 = 0.28, p < 0.001) with a weaker negative correlation between the SS length and maximal length of the FO floor (R2 = 0.02, p < 0.001). The groups showed similar atrial dimensions and volumes. Present in a third of patients, hearts with LASP have longer SS and overlapping SP.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation.

BACKGROUND: Anti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. OBJECTIVES: This study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. METHODS: Forty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. RESULTS: There were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = - .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = - .434, P = .039). CONCLUSION: Our study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

Localization of myocardial FDG uptake for prognostic risk stratification in corticosteroid-naïve cardiac sarcoidosis.

BACKGROUND: The localization of myocardial 18F-fluorodeoxyglucose (FDG) uptake affecting long-term clinical outcomes has not been elucidated in patients with corticosteroid-naïve cardiac sarcoidosis (CS). OBJECTIVES: This study sought to investigate the localization of myocardial FDG uptake on positron emission tomography (PET) and myocardial perfusion abnormality to predict adverse events (AEs) for a long-term follow-up in patients with corticosteroid-naïve CS. METHODS: Consecutive 90 patients with clinical suspicion of CS who underwent FDG-PET imaging to assess for inflammation were enrolled. AEs were defined as a composite of sustained ventricular tachycardia (VT), heart transplantation, and all-cause death, which were ascertained by medical records, defibrillator interrogation, and telephone interviews. RESULTS: Of 90 patients, 42 patients (mean age 62.9 ± 12.0 years; 76.2% females) were confirmed active cardiac involvement. Over a median follow-up of 4.9 years, 15 patients with CS experienced AEs including 6 sustained ventricular tachycardias (VT) and 9 deaths. Cox proportional-hazards model after adjustment for left ventricular systolic dysfunction revealed that FDG uptake in the right ventricle (RV) or basal anterolateral area of the left ventricle (LV) with myocardial perfusion abnormality was predictive of AEs. CONCLUSIONS: FDG uptake in the RV or basal anterolateral area of the LV with myocardial perfusion abnormality provides long-term prognostic risk stratification in patients with corticosteroid-naïve CS.

Vascular/perivascular inflammation in IgG4-related disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is characterized by the infiltration of IgG4-positive plasma cells and fibrosclerotic inflammation in multiple organs. Although vascular complications are present in some patients with IgG4-RD, vascular and/or perivascular inflammatory activity compared to control subjects remains unknown. This study sought to investigate vascular/perivascular inflammation in IgG4-RD patients compared to control subjects using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography (FDG-PET/CT). METHODS: We examined 37 consecutive patients diagnosed as IgG4-RD (29 males, mean age of 64.3 ± 8.3 years old), who underwent FDG-PET/CT. Thirty-seven age- and gender-matched subjects without IgG4-RD were employed as controls. Vascular/perivascular inflammation was quantified by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). RESULTS: All IgG4-RD patients presented with multiple region involvements. Twelve (32.4%) of the IgG4-RD patients had vascular complications, all of which appeared in the abdominal aorta. IgG4-RD patients had significantly higher TBR values in the descending aorta, abdominal aorta, and common iliac artery than control subjects. Also, IgG4-RD patients with vascular complication exhibited higher TBR values in the infra-renal aorta and common iliac artery than those without vascular complication. CONCLUSIONS: We found that vascular FDG activity is significantly elevated in IgG4-RD patients regardless of vascular complication than control subjects. FDG-PET/CT is a useful modality for assessing vascular/perivascular inflammation, which may contribute vascular complication in IgG4-RD patients.

Two-hour postload plasma glucose and pigment epithelium-derived factor levels are markers of coronary artery inflammation in type 2 diabetic patients.

BACKGROUND: We have previously found that pioglitazone attenuates inflammation in the left main trunk of coronary artery (LMT), evaluated as target-to-background ratio (TBR) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with impaired glucose tolerance or type 2 diabetes. OBJECTIVES: We assessed which clinical variables could predict the change in TBR in the LMT after 4-month add-on therapy with oral hypoglycemic agents (OHAs). METHODS: A total of 38 type 2 diabetic patients with carotid atherosclerosis who had already received OHAs except for pioglitazone was enrolled. At baseline and 4 months after add-on therapy with pioglitazone or glimepiride, all patients underwent 75 g oral glucose tolerance test, blood chemistry analysis, and FDG-PET/CT. RESULTS: Fasting plasma glucose, 30-, 60-, 90-, 120-minutes postload plasma glucose, HbA1c, and LMT-TBR values were significantly decreased by add-on therapy, whereas high-density lipoprotein-cholesterol and adiponectin levels were increased. Increased serum levels of pigment epithelium-derived factor (PEDF), a marker of insulin resistance and non-use of aspirin at baseline could predict the favorable response of LMT-TBR to add-on therapy. Moreover, Δ120-minutes postload plasma glucose and ΔPEDF were independent correlates of ΔLMT-TBR. CONCLUSIONS: Our present study suggests that 120-minutes postload plasma glucose and PEDF values may be markers and potential therapeutic targets of coronary artery inflammation in type 2 diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov . Unique identifier: NCT00722631. New markers for diabetes and CAD is on the horizon! Two-hour postload plasma glucose and pigment epithelium derived factor are markers of coronary artery inflammation in type 2 diabetic patients.

Long-term survival outcome for pre-capillary pulmonary hypertension at a Japanese single center.

In recent years, several treatment options for patients with pre-capillary pulmonary hypertension (PH) have improved the short-term prognosis. However, the long-term survival for pre-capillary PH has not been well investigated. This study sought to investigate the long-term survival for pre-capillary PH in Kurume University Hospital. A total of 144 patients with pre-capillary PH (110 women, mean age 55.1 ± 17.9 years) were enrolled. The maximal duration of followup was 15 years with a mean followup of 5.77 years. The 15 year survival was 59.1% for pre-capillary PH, 68.5% for pulmonary arterial hypertension (PAH), and 44.3% for chronic thromboembolic PH. The 5 year survival was 50.9% for PH due to lung disease (PH-LD), indicating the worst in the pre-capillary PH subgroups. The survival for portopulmonary hypertension was the lowest among PAH groups, and PAH associated with connective tissue disease and congenital heart disease decreased 10 years after diagnosis. A 6 min walk distance and elevated brain natriuretic peptide were significantly associated with survival outcome in pre-capillary PH patients and diastolic pulmonary arterial pressure was related to survival for PH-LD. The survivals were different among pre-capillary PH groups in our hospital. Above all, the long-term survival was better than in previous reports.

Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo 111In-GSAO SPECT.

BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion. METHODS: Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (111In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization. RESULTS: Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals. CONCLUSIONS: This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.

Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Is Associated With Endothelial Dysfunction.

OBJECTIVE: Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. APPROACH AND RESULTS: We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Δ%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Δ%FMD and ΔTBR; ΔTBR was a sole independent associate of Δ%FMD in hypertensive patients (r=-0.558; P<0.001). CONCLUSIONS: The present study showed that vascular inflammation in the carotid arteries evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.

Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects.

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.