Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease.

OBJECTIVES: Cerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD. METHODS: We evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients' clinical details. RESULTS: CMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 - 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 - 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables. CONCLUSIONS: CMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.

Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Relation of Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Nutritional Status and Prognosis in Patients With Acute Heart Failure.

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR<1.16 (n = 262); second tertile, 1.16≤AAR<1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p < 0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF.

Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction.

BACKGROUND: B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure, its severity, and prognosis. However, little is known about factors related to disproportionately low BNP levels even during acute heart failure conditions. METHODS AND RESULTS: Among 424 patients hospitalized for acute heart failure, we categorized the patients into the HFpEF (LVEF > 50%) or HFrEF (LVEF ≤ 50%) group and subdivided them into disproportionately low BNP (LB) group and high BNP (HB) group using a cut-off BNP level of 200 pg/mL at admission. The proportion of patients with LB was higher in the HFpEF group (22.2%) than in the HFrEF group (10.9%, p = 0.002). Patients with LB had a high BMI, lower blood pressure, and history of previous cardiovascular surgery in the HFpEF group, while patients in the HFrEF group had a high BMI and smaller left ventricular end-diastolic volume index. Furthermore, presence of LB in the HFrEF group was related to good prognosis, but LB in the HFpEF group was an indicator of poor prognosis as HB group. CONCLUSIONS: The factors associated with LB were different between the HFpEF and HFrEF groups. LB was related to good prognosis in HFrEF, but not in HFpEF.

Left atrial spontaneous echo contrast occurring in patients with low CHADS2 or CHA2DS2-VASc scores.

BACKGROUND: Left atrial spontaneous echo contrast (LASEC) is common in patients with atrial fibrillation (AF), although scarce information exists on LASEC occurring in nonvalvular AF patients who have low thromboembolic risk scores. We therefore examined prevalence and determinants of LASEC under low CHADS2 or CHA2DS2-VASc scores in these patients. METHODS: Among 713 patients who underwent transesophageal echocardiography, 349 with a CHADS2 score < 2 (CHADS2 group) (93 women, mean age 65 years) and 221 with a CHA2DS2-VASc score < 2 (CHA2DS2-VASc group) (39 women, mean age 62 years) were separately examined for clinical and echocardiographic findings. RESULTS: LASEC was found in 77 patients of CHADS2 group (22%) and in 41 of CHA2DS2-VASc group (19%). Multivariate logistic regression analysis, adjusted for several parameters including non-paroxysmal AF, LA enlargement (LA diameter ≥ 50 mm), left ventricular (LV) hypertrophy, and an elevated B-type natriuretic peptide (BNP) (BNP ≥200 pg/mL) revealed that for CHADS2 group, non-paroxysmal AF (Odds ratio 5.65, 95%CI 3.08-10.5, P < 0.001), BNP elevation (Odds ratio 3.42, 95%CI 1.29-9.06, P = 0.013), and LV hypertrophy (Odds ratio 2.26, 95%CI 1.19-4.28, P = 0.013) were significant independent determinants of LASEC, and that for CHA2DS2-VASc group, non-paroxysmal AF (Odds ratio 3.38, 95%CI 1.51-7.54, P = 0.003) and LV hypertrophy (Odds ratio 2.53, 95%CI 1.13-5.70, P = 0.025) were significant independent determinants of LASEC. CONCLUSIONS: LASEC was present in a considerable proportion of patients with nonvalvular AF under low thromboembolic risk scores. Information on AF chronicity, BNP, and LV hypertrophy might help identify patients at risk for thromboembolism, although large-scale studies are necessary to confirm our observations.

Usefulness of tissue Doppler-derived atrial electromechanical delay for identifying patients with paroxysmal atrial fibrillation.

BACKGROUND: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. METHODS: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A' for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. RESULTS: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P < 0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03-1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44-3.51, P < 0.001), was one of the significant independent associates of identifying PAF patients. CONCLUSIONS: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.

Prognostic impact of a novel index of nutrition and inflammation for patients with acute decompensated heart failure.

Malnutrition and systemic inflammation are associated with poor outcomes in patients with heart failure. Recent studies have reported that the advanced lung cancer inflammation index (ALI), derived from the body mass index (BMI), serum albumin level, and neutrophil-to-lymphocyte ratio (NLR), is associated with poor prognosis in several types of cancers. Each marker is also known to prognostic factor of heart failure. Therefore, we hypothesized that ALI may be useful for determining the prognosis of patients with acute decompensated heart failure (ADHF). We reviewed survival in 381 consecutive patients (age, 73.1 ± 11.4 years, 59% men) who were hospitalized for ADHF and discharged. ALI at discharge, calculated as BMI × albumin level/NLR, was used to divide the patients into tertiles (ALI < 23.88, 23.88 ≤ ALI < 42.43, and ALI ≥ 42.43). The patients were also stratified into six groups according to the ALI tertiles and median concentration (177 pg/mL) of brain natriuretic peptide (BNP). The primary endpoint comprised all-cause mortality and readmission because of heart failure. The median follow-up duration was 363 days (interquartile range: 147-721 days), and 166 patients (44%) experienced the primary endpoint. Kaplan-Meier analysis showed that the event rate decreased progressively from the first to the third ALI tertile (52%, 48%, and 31%, respectively; p = 0.0013). In a multivariate Cox proportional hazards model, the first tertile was an independent prognostic factor for the primary endpoint (third vs. first tertile: hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; p = 0.031). The hazard ratio for the primary endpoint for the patients with high BNP and first tertile ALI relative to the patients with low BNP and third tertile ALI was 5.3 (95% confidence interval, 2.9-9.5; p < 0.001). ALI at discharge, a novel and simple index of nutrition and inflammation, may be useful for risk stratification and predicting the prognosis of patients with ADHF.

Correction to: Increased prevalence of cerebral microbleeds in patients with low left ventricular systolic function.

In the original publication of the article, under the results section, the following sentence.

Increased prevalence of cerebral microbleeds in patients with low left ventricular systolic function.

Gradient-echo T2-star (T2*)-weighted magnetic resonance imaging (MRI) is a sensitive method to detect cerebral microbleeds (CMBs). The presence of CMBs was reported to be a marker of future cardiovascular mortality and is associated with various cardiovascular risk factors, use of antithrombotic drugs, and cognitive dysfunction. However, the relationship between cardiac function and CMBs remains unclear. We investigated the association between cardiac function and presence of CMBs in patients with cardiovascular diseases. This single-center retrospective study included a total of 424 participants (mean age 70 ± 12 years; men 286 (67%); mean left ventricular ejection fraction (LVEF) 61% ± 12%] who underwent echocardiography and brain T2*-weighted MRI within 1 month without neurologic abnormality. CMBs were found in 118 (28%) patients. There was no significant relationship between CMBs and anticoagulant or antiplatelet therapy. LVEF was significantly lower in patients with CMBs than in those without CMBs (59% ± 13% vs. 62% ± 11%, P < 0.05). On multivariate logistic analysis, lower LVEF [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00; P < 0.05] and age (OR 1.02, 95% CI 1.00-1.05; P < 0.05) were significantly associated with CMBs. The presence of CMBs was frequently observed in the patients with cardiovascular disease and was significantly associated with age and LVEF.

Fibrosis-4 index reflects right-sided filling pressure in patients with heart failure.

The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63-80] vs. 65 [IQR, 56-74] years, P < 0.001) and had higher right atrial pressure (RAP; 7 [IQR, 5-11] vs. 4 [IQR, 1-6] mmHg, P < 0.001) and pulmonary capillary wedge pressure (16 [IQR, 12-22] vs. 12 [IQR, 8-19] mmHg, P = 0.011) than those with a low FIB-4 index. The FIB-4 index correlated more strongly with parameters of right-sided than left-sided HF (RAP, R = 0.41, P < 0.001; inferior vena cava diameter, R = 0.44, P < 0.001; pulmonary capillary wedge pressure, R = 0.15, P = 0.038; brain natriuretic peptide, R = 0.14, P = 0.29). Multiple regression analysis showed that the FIB-4 index independently correlated with RAP. In conclusion, the FIB-4 index can non-invasively reflect right-sided filling pressure, which might explain why it is associated with a poor prognosis, among patients with heart failure.

Left Atrial Ball-Shaped Thrombus with Concomitant Biatrial Appendage Thrombi in a Patient with Prior Mitral Valve Replacement.

We reported a 67-year-old woman in whom large atrial thrombi were found by chance during discontinuation of therapeutic anticoagulation. The patient, with a history of mitral valve replacement surgery, had stopped anticoagulation for months because of intractable gastrointestinal bleeding, during which she was found to have 3 large thrombi in the atria on transesophageal echocardiography: left atrial free-floating ball-shaped thrombus, left atrial appendage thrombus, and right atrial appendage thrombus. One month following diagnosis, she still had the free-floating thrombus despite adequate anticoagulation. Free-floating ball-shaped thrombus is a rare finding observed on echocardiography in patients with mitral valve disease and an even rarer finding in case of appendage thrombi coexisting.

IgG4-Positive Plasmacytic Infiltration in Aortic Wall and Aortic Valve Surgical Samples and Its Relation to Preoperative Serum IgG4 Levels.

The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.

Chronic Kidney Disease as a Possible Predictor of Left Atrial Thrombogenic Milieu Among Patients with Nonvalvular Atrial Fibrillation.

Patients with chronic kidney disease (CKD) experiencing atrial arrhythmia are hypothesized to have elevated CHADS2 and CHA2DS2-VASc scores, thereby predisposed to left atrial (LA) thrombus formation and subsequent thromboembolism. We examined possible association of LA thrombogenic milieu (TM) with CKD in patients with nonvalvular atrial fibrillation. A total of 581 patients (181 women; mean age, 67 years) who underwent transesophageal echocardiography were examined. Patients were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2): eGFR ≥90 (n = 29), 60≤ eGFR <90 (n = 329), 30≤ eGFR <60 (n = 209), and eGFR <30 (n = 14). TM was defined as the presence of LA thrombus, dense spontaneous echo contrast, or LA appendage velocity ≤25 cm/s. Of 581 patients, 147 (25%) had TM. The prevalence of TM increased with decreasing eGFR (4%, 18%, 36%, and 86% for each group, p <0.001). Similar trends were observed for some of the clinical and echocardiographic variables including CHA2DS2-VASc score and LA size. Multivariate logistic regression analysis revealed that every 10 ml/min/1.73 m2 decrement in eGFR was a significant independent correlate of TM (odds ratio 0.80, p = 0.005), along with nonparoxysmal atrial fibrillation (AF) (odds ratio 0.45, p = 0.004), higher CHA2DS2-VASc score (odds ratio 1.24, p = 0.012), every 5 ml/m2 increment in LA volume index (odds ratio 1.57, p <0.001), and every 10% decrement in left ventricular ejection fraction (odds ratio 0.51, p <0.001). In conclusion, CKD may be a significant risk factor for LA thrombus formation in patients with nonvalvular atrial fibrillation.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) with an Unusual Manifestation of Mid-Ventricular Obstruction Caused by Endocardial Thrombus.

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Intracardiac thrombosis is one of the major cardiac complications in EGPA that may cause thromboembolism. CASE REPORT A 46-year-old male presenting with intermittent chest pain and numbness of the lower extremities was admitted to our center. His case was complicated by multiple brain infarcts and endocardial thrombosis in the left ventricle. A condition of restrictive cardiomyopathy was also found. After a thorough workup, he was diagnosed with antineutrophil cytoplasmic antibody (ANCA) positive EGPA. Interestingly, the thrombus was accompanied by a pressure gradient producing mid-ventricular obstruction. The patient improved reasonably with immunosuppression and anticoagulation treatment, in addition to heart failure treatment, and had a concomitant regression of the thrombus and reduction of the pressure gradient. CONCLUSIONS For an EGPA patient complicated by intraventricular obstruction caused by endocardial thrombosis, which could accelerate the release of the thrombus into the systemic circulation resulting in a life-threating condition, timely and aggressive measures against cardioembolic complications should be considered.

A Case of Aortic Stenosis with Serum IgG4 Elevation, and IgG4-Positive Plasmacytic Infiltration in the Aortic Valve, Epicardium, and Aortic Adventitia.

A 74-year-old man was admitted for preoperative screening of aortic stenosis. Five months before this admission, he was found to have elevated serum immunoglobulin G4 (IgG4; 2,010 mg/dL). Computed tomography (CT) showed a soft tissue mass surrounding the abdominal aorta, suggestive of IgG4-related periaortitis. CT coronary angiography showed perivascular thickening of the right coronary artery, and subsequent coronary angiography showed a multi-vessel disease. The patient underwent aortic valve replacement and coronary bypass surgery. Immunohistochemical analysis showed IgG4-positive plasmacytic infiltration in specimens from the aortic valve, epicardium, and aortic adventitia, suggestive of the possible role of IgG4-related immune inflammation for the pathogenesis.

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.).

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.