Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction.

BACKGROUND: Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward. CONCLUSIONS: After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

Basal wall hypercontraction of Takotsubo cardiomyopathy in a patient who had been diagnosed with dilated cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy is characterized by the basal hypercontractility and apical ballooning of the left ventriculum and T-wave inversion in the electrocardiogram. It has been suggested that Takotsubo cardiomyopathy might underlie the pathogenesis of persistent cardiac dysfunction; however, few reports are present demonstrating the advent of Takotsubo cardiomyopathy in patients with idiopathic cardiomyopathy. CASE PRESENTATION: A 64-year-old women was admitted due to dyspnea on effort and lower extremity edema. She had been diagnosed with idiopathic dilated cardiomyopathy 2.5 years before owing to the reduced left ventricular ejection fraction (24%), normal coronary artery, and interstitial fibrosis of the myocardial samples. On admission, her electrocardiogram showed giant negative T wave in II, III, aVF, and precordial leads. Echocardiography showed dyskinesis of the left ventricular apex and hypercontraction of the basal wall, which had not been observed in the previous examinations. Coronary angiography showed normal coronary arteries, and apical ballooning and basal hypercontractility was confirmed by left ventriculography. On day 15 of admission, contraction of apical wall was recovered, and basal hypercontraction was disappeared. CONCLUSION: The present case is the first report demonstrating appearance the transient basal wall hypercontraction along with the advent of Takotsubo cardiomyopathy in a patient diagnosed with dilated cardiomyopathy. Whether such findings are indicative of fair prognosis and have the utility of understanding the pathogenesis of dilated cardiomyopathy needs further investigation.

Association between suPAR and cardiac diastolic dysfunction among patients with preserved ejection fraction.

Serum levels of the soluble urokinase-type plasminogen activator receptor (suPAR) reflect immune and inflammatory activation, and are shown to be associated with cardiovascular outcomes. We herein investigated the potential association between suPAR and left ventricular diastolic dysfunction among patients with preserved left ventricular ejection fraction (LVEF) and sinus rhythm. Among 291 patients who had sinus rhythm and an LVEF of ≥50% enrolled in the study, 26 (8.9%) were considered to have diastolic dysfunction. Patients with diastolic dysfunction had lower estimated glomerular filtration rate (eGFR), and higher systolic blood pressure (BPs), BNP, C-reactive protein, and suPAR than those without diastolic dysfunction. As compared with the first suPAR quartile, the fourth suPAR quartile was significantly associated with both diastolic dysfunction with an odds ratio of 8.95 [95% confidence interval (CI), 1.04-77.0, P < 0.05] after adjusting for sex, age, BPs log(eGFR), CRP, and diuretic use. On the other hand, receiver-operating characteristic curve (ROC) analysis showed that addition of log(suPAR) to the combination of age, sex, and log(eGFR), CRP, and diuretic use did not significantly improve the prediction of diastolic dysfunction. Among cardiac patients with preserved LVEF, serum suPAR was associated with diastolic dysfunction independent of confounding factors by logistic regression analysis. However, according to the ROC analysis, the utility of suPAR as a biomarker for diastolic dysfunction may be limited from a clinical point of view.

Plasma Pentraxin3 Level Is Associated With Plaque Vulnerability Assessed by Optical Coherence Tomography in Patients With Coronary Artery Disease.

The role of pentraxin 3 (PTX3) has been implicated in the process of plaque vulnerability. However, few studies have addressed the direct relationship between plaque morphology and plasma PTX3. We evaluated the relationship between coronary vulnerable plaque, assessed by optical coherence tomography (OCT), and plasma PTX3 in patients with coronary artery disease (CAD).OCT was used to determine plaque vulnerability in 51 patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS; n = 17) and stable angina (SA; n = 34). Both highly-sensitive C-reactive protein and systemic plasma PTX3 were measured.Based on the OCT findings, patients were divided into 3 groups; a fibrous plaque (n = 18), thick-cap fibroatheroma (ThCFA) (n = 19), and thin-cap fibroatheroma (TCFA) (n = 14) groups. ThCFA was defined as a lipid-rich plaque (lipid content in ≥ 2 quadrant) covered with ≥ 65 µm thick fibrous cap, and TCFA was that with < 65 µm. There were no differences in patient characteristics between the 3 groups except for the presence of ACS and eicosapentaenoic acid levels. TCFA was more frequently observed with plaque rupture and intraluminal thrombus compared with the other 2 groups. Plasma PTX3 levels were higher in the TCFA group compared with the fibrous plaque and ThCFA groups, and showed weak correlation with cap thickness.Plasma PTX3 level was associated with plaque vulnerability assessed by OCT in patients with CAD.

Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-infiltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (≥135 mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic findings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91-98.).

The Prevalence and Findings of Subclinical Influenza-associated Cardiac Abnormalities among Japanese Patients.

Objective Although life-threatening cardiac complications in influenza infection are rare, subclinical influenza-associated cardiac abnormalities may occur more frequently. We investigated the prevalence of subclinical cardiac findings. Methods After obtaining their written informed consent, 102 subjects were enrolled in the present study. The study subjects underwent a first set of examinations, which included electrocardiography (ECG), echocardiography, and the measurement of their cardiac enzyme levels. Those with one or more abnormal findings among these examinations were encouraged to undergo a repeat examination 2 weeks later. Results Among the 102 subjects enrolled, 22 (21.6%) were judged to have cardiac findings, including ST-T abnormalities, pericardial effusion, diastolic dysfunction, and cardiac enzyme elevation. Eighteen of these 20 subjects underwent a second screening at a median of 14 days later, and it was found that 11 of the 18 subjects were free from cardiac findings on this second examination. This suggested that the abnormalities were only transient and they therefore might have been associated with influenza. Approximately 20% of the influenza patients enrolled had cardiac findings, including ST-T segment abnormalities, pericardial effusion, and cardiac enzyme elevation. Conclusion Among the 102 patients who were studied, the cardiac findings were only mild and transient; however, physicians should be aware of influenza infection-associated cardiac abnormalities because such abnormalities may not be rare.

High serum bilirubin is associated with lower prevalence of peripheral arterial disease among cardiac patients.

Several studies have shown that subjects with higher serum bilirubin may have a lower risk of cardiovascular disorders. We herein investigated whether serum bilirubin concentration is associated with lower extremity ischemia among cardiology patients. In total, 935 patients without a history of angioplasty or bypass surgery of the lower limb arteries and who had bilateral ankle-brachial index measurements were included in the study. Peripheral arterial disease (PAD) was defined to be present when ABI of either or both sides was <0.9. Overall, the serum total bilirubin concentration ranged between 0.1 and 2.7mg/dL (normal range, 0.1-1.0mg/dL). Across the bilirubin tertiles, age did not differ significantly. On the other hand, male patients (median 0.6mg/dL, interquartile range (IQR) 0.4-0.7mg/dL) had significantly higher bilirubin levels than female patients (median 0.5mg/dL, IQR 0.4-0.7mg/dL, P=0.014). Logistic regression analysis showed that, as compared with the lowest bilirubin tertile (0.1-0.4mg/dL), the highest tertile (0.7-2.7mg/dL) was significantly negatively associated with prevalent PAD after adjusting for sex, age, eGFR, white blood cell count, inorganic phosphate, HbA1C, total and HDL cholesterol, triglycerides, current smoking, diabetic medication, and statin use. This association remained significant when only those with serum bilirubin in the normal range were included in the analysis. Among cardiology patients, serum bilirubin concentration was significantly negatively associated with prevalence of PAD. The underlying mechanism and therapeutic indications should be investigated in further investigations.

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level.

BACKGROUND: Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. PURPOSE: We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. METHODS AND RESULTS: In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P<0.001), LVMI (R = 0.16, P = 0.014) and BNP (R = 0.46, P<0.001). In logistic regression analysis, the highest suPAR tertile (> 3236 pg/mL) was associated with low LVEF (< 50%) and elevated BNP (> 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22-12.1) and 5.36 (95% CI, 1.32-21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). CONCLUSIONS: suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis.

Association between serum soluble urokinase-type plasminogen activator receptor and atrial fibrillation.

BACKGROUND: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. METHODS: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. RESULTS: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis showed that, as compared with the lowest suPAR quartile, the highest suPAR quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence interval, 1.71-24.5) after adjustment for sex, age, log(eGFR), C-reactive protein, and systolic blood pressure. In multivariate receiver operating characteristic analysis to predict NPAF, the area under the curve (AUC) for the combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction (AUC, 0.812; SE, 0.034, P=0.084). CONCLUSIONS: Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies.

Takotsubo cardiomyopathy caused by acute respiratory stress from extubation: A case report.

RATIONAL: Takotsubo cardiomyopathy (TCM) is a transient systolic dysfunction of the left ventricular apex without stenosis of coronary arteries and is induced by various psychological and physical factors. TCM sometimes causes lethal complications such as arrhythmia, thrombogenesis, and even cardiac rupture, and thus it should be diagnosed appropriately and managed carefully. Intensive care unit (ICU) patients are exposed to overstress during the treatment process and therefore can are at potential risk for TCM. PATIENT CONCERNS: The patient was diagnosed as having pneumonia because of influenza A virus mixed with bacteria and underwent intensive care with intubation and mechanical ventilation in the ICU. His respiratory condition soon improved, and so extubation was carried out; however, redeterioration with pulmonary edema occurred at half of a day following extubation. DIAGNOSIS: The chest x-ray revealed pulmonary edema. The electrocardiogram pattern significantly changed with time, and the echocardiogram showed weakness of wall motion around the left ventricular apex. Hence, to confirm the diagnosis, we performed cardiac catheterization immediately, with the results showing a Takotsubo-like form at the systolic phase without significant stenosis of the coronary arteries. INTERVENTION: The patient was reintubated with administration of catecholamine for decreasing blood pressure caused by left ventricular dysfunction. Also, diuretics for pulmonary edema and anticoagulants for prevention of thrombogenesis were administered. OUTCOMES: As the respiratory condition improved with stabilization of cardiovascular hemodynamics, reextubation was done at ICU day 11 and was discharged from the ICU at ICU day 15. The patient was subsequently treated for pneumonia after leaving the ICU but suffered from repetitive aspiration pneumonia and was finally transferred to another hospital at hospital day 111. LESSONS: TCM should be considered especially under the situation of intensive care, and prompt diagnosis should be followed by appropriate management.

Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients.

BACKGROUND AND PURPOSE: Xanthine oxidoreductase (XOR), which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA) synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients. METHODS AND RESULTS: Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI), alanine aminotransferase (ALT), HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD), those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF) and increased plasma B-type natriuretic peptide (BNP) levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages. CONCLUSIONS: Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

Primary Leiomyosarcoma in the Inferior Vena Cava Extended to the Right Atrium: A Case Report and Review of the Literature.

A 38-year-old woman had developed an abdominal distention, lower extremity edema, and dyspnea. Imaging examination revealed a large mass in the right atrium which was connected to lesions within the inferior vena cava. Although complete resection of the mass was not possible, partial surgical tumor resection was performed to avoid pulmonary embolization and circulatory collapse. Leiomyosarcoma was diagnosed histologically, and chemotherapy (doxorubicin) followed by radiotherapy was started. By reviewing papers published in the past 10 years that included 322 patients, we also discuss the clinical presentations and prognosis of leiomyosarcoma in the inferior vena cava.

Plaque-stabilizing effect of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker in a rabbit plaque model.

AIM: Previous studies have revealed that blockade of the renin angiotensin system attenuates plaque vulnerability and reduces cardiovascular events; however, few studies have compared the effects of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) and evaluated combination therapy. The objective of this study was to compare the efficacy and mechanisms of plaque stabilization by ACEI or ARB and to determine the effects of combination therapy. METHODS: Twenty-eight male Japanese white rabbits were fed a high-cholesterol diet after balloon injury of the carotid arteries, then separated into ACEI (n= 7; imidapril 0.5 mg/kg/day), ARB (n= 7; TA606 4.5 mg/kg/day), combination (n= 7; imidapril 0.5 mg/kg/day+TA606 4.5 mg/kg/day), and vehicle (n= 7) groups. RESULTS: No difference in plaque volume was identified among the 4 groups. ACEI or ARB increased the thickness of the fibrous cap, collagen content and the number of smooth muscle cells in the intima (% smooth muscle cell in intima: ACEI, 36.3%; ARB, 36.4%; vehicle, 14.9%), and reduced the accumulation of macrophages (% macrophages in intima: ACEI, 20.1%; ARB, 24.0%; vehicle, 37.9%), suggesting the plaque-stabilizing effects of each drug. ACEI reduced matrix metalloproteinase (MMP)-9 expression and gelatinolytic activity in the intima. While ARB did not change gelatinolytic activity, accumulation ot T cell in the intima was suppressed. Combination therapy did not show additive effects. CONCLUSION: These results suggest that ACEIs and ARBs have similar, but not additive, plaque-stabilizing effects. Each agent showed specific effects, with ACEIs decreasing gelatinolytic activity and ARBs suppressing T cell accumulation.

Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice.

BACKGROUND: Valvular aortic stenosis (AS) is not an infrequent condition in the aged population. Activation of renin-angiotensin system (RAS) is presumed to be involved in the development of AS; however, direct evidence seems to be limited. We herein examined the effect of the administration of angiotensin II (Ang II) on the development of aortic valve thickening in apolipoprotein-E (ApoE)-deficient mice. METHODS AND RESULTS: Male ApoE-deficient mice were divided into three groups: control (saline, n = 8), mice that were administered low-dose Ang II (500 ng/kg/min, n = 11), and those with high-dose Ang II (1000 ng/kg/min, n = 11) administration for 4 weeks. Administration of high-dose, but not low-dose, Ang II significantly induced aortic valve thickening. It was found that in the aortic valve leaflets of high-dose Ang II group, integrity of endothelial cells was impaired and the number of myofibroblasts was increased. These phenomena induced by high-dose Ang II were suppressed by Ang II type 1 receptor blocker olmesartan (n = 15), but not by the dilatator, hydralazine (n = 13). Olmesartan also suppressed dilatation of aortic diameter, although it did not significantly affect the plaque area, in the abdominal aorta in ApoE-deficient mice. CONCLUSION: Administration of Ang II to genetically hyperlipidemic mice induced aortic valve thickening by a pressor-independent mechanism. Role of RAS activation in the development of AS in dyslipidemic patients should further be investigated.