Relationship between Cardiac Acoustic Biomarkers and Pulmonary Artery Pressure in Patients with Heart Failure.

Since an elevation of pulmonary artery pressure (PAP) often precedes clinical worsening of heart failure (HF), early and non-invasive detection of this sign is useful in HF care. This study aimed to assess whether cardiac acoustic biomarkers (CABs) are associated with the elevation of PAP in patients with HF. Patients with HF scheduled to undergo right heart catheterization were prospectively enrolled. CABs were concurrently recorded during catheterization at rest (baseline) and while applying a handgrip (exercise). Forty-nine patients were included in the analysis, and their mean PAP significantly increased after exercise compared to baseline. Several CABs correlated significantly with mean PAP by absolute values, among which S2 Width (r = 0.354; p = 0.014 and r = 0.363; p = 0.010) and S3 Strength (r = 0.375; p = 0.009 and r = 0.386; p = 0.007) were consistent throughout baseline and exercise. The response of CABs to exercise-induced PAP elevation was divided into two patterns: increasing and decreasing. The frequency of cardiac index below 2.2 mL/m2 was significantly higher in the decreasing pattern. CABs related to S2 and S3 showed significant correlations with absolute PAP values both at baseline and after exercise in patients with HF, but no significant correlations between their changes from baseline to post-exercise were observed in this study population. Further research is therefore needed to assess whether CABs can sensitively reflect changes in PAP according to HF status and underlying phenotypes.

Cardiac acoustic biomarkers as surrogate markers to diagnose the phenotypes of pulmonary hypertension: an exploratory study.

Pulmonary hypertension (PH) is commonly associated with left heart disease. In this retrospective study, using the database of a clinical study conducted between January 2008 and July 2008, the phenotypes of PH were classified using non-invasive cardiac acoustic biomarkers (CABs) and compared with classification by echocardiography. Records with same-day measurement of acoustic cardiography and right heart catheterization (RHC) parameters were included; cases with congenital heart disease were excluded. Using the RHC measurements, PH was classified as pre-capillary PH (Prec-PH), isolated post-capillary PH (Ipc-PH), and combined pre-capillary and post-capillary PH (Cpc-PH). The first, second, third, and fourth heart sounds (S1, S2, S3, and S4) were quantified as CABs (intensity, complexity, and strength). Forty subjects were selected: 5 had Prec-PH, 5 had Ipc-PH, 8 had Cpc-PH, and 22 had No-PH. CABs were significantly correlated with RHC measurements, with significant differences among phenotypes. Phenotype classification was performed using various CABs, and the diagnostic performance as assessed by the area under the receiver operating characteristic curve was 0.674-0.720 for Prec-PH, 0.657-0.807 for Ipc-PH, and 0.742 for Cpc-PH. High negative and low positive predictive values for phenotype identification were observed. CABs may provide an ambulatory measurement method with home-monitoring friendliness which is more convenient than standard examinations to identify presence of PH and its phenotypes.

Simple risk-score model for in-hospital major bleeding based on multiple blood variables in patients with acute myocardial infarction.

BACKGROUND: In-hospital bleeding is associated with poor prognosis in patients with acute myocardial infarction (AMI). We sought to investigate whether a combination of pre-procedural blood tests could predict the incidence of in-hospital major bleeding in patients with AMI. METHODS AND RESULTS: A total of 1684 consecutive AMI patients who underwent primary percutaneous coronary intervention (PCI) were recruited and randomly divided into derivation (n = 1010) and validation (n = 674) cohorts. A risk-score model was created based on a combination of parameters assessed on routine blood tests on admission. In the derivation cohort, multivariate analysis revealed that the following 5 variables were significantly associated with in-hospital major bleeding: hemoglobin level < 12 g/dL (odds ratio [OR], 3.32), white blood cell count >10,000/µL (OR, 2.58), platelet count <150,000/µL (OR, 2.51), albumin level < 3.8 mg/dL (OR, 2.51), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR, 2.31). Zero to five points were given according to the number of these factors each patient had. Incremental risk scores were significantly associated with a higher incidence of in-hospital major bleeding in both cohorts (P < 0.001). Receiver operating characteristic curve analysis of risk models showed adequate discrimination between patients with and without in-hospital major bleeding (derivation cohort: area under the curve [AUC], 0.807; 95% confidence interval [CI], 0.759-0.848; validation cohort: AUC, 0.793; 95% CI, 0.725-0.847). CONCLUSIONS: Our novel laboratory-based bleeding risk model could be useful for simple and objective prediction of in-hospital major bleeding events in patients with AMI.

Serum Albumin and Bleeding Events After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction (from the HAGAKURE-ACS Registry).

Low serum albumin (SA) on admission in patients with acute myocardial infarction (AMI) has been reported to be associated with adverse cardiovascular events. The relation between low SA and post-AMI bleeding events is presently unknown. We analyzed 1,724 patients with AMI enrolled in the HAGAKURE-ACS registry who underwent primary percutaneous coronary intervention from January 2014 to December 2018. To assess the influence of low SA at admission, patients were divided into 3 groups according to the albumin tertiles: the low SA group (<3.8 g/100 ml), the middle SA (MSA) group (3.8 to 4.1 g/100 ml), and the normal SA (NSA) group (≥4.2 g/100 ml). The primary end point was the incidence of Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries moderate/severe bleeding. The cumulative 3-year incidence of the primary end point was significantly higher in the low SA group than in the MSA and NSA groups (30.8% and 11.9% vs 7.7%; p <0.001). In the landmark analysis at 30 days, the cumulative incidences of the primary end point were also significantly higher in the low SA group than in the MSA and NSA groups, both within and beyond 30 days (20.1% and 6.1% vs 3.5%; p <0.001, and 12.4% and 6.2% vs 4.5%; p <0.001, respectively). After adjusting for confounders, the low SA group showed excess risk of bleeding events relative to NSA (hazard ratio 1.56; 95% confidence interval 1.06 to 2.30; p = 0.026), whereas risk of bleeding was neutral in MSA relative to NSA (hazard ratio 0.94; 95% confidence interval 0.63 to 1.34; p = 0.752). In conclusion, low SA at admission was independently associated with higher risk for bleeding events in patients with AMI undergoing percutaneous coronary intervention.

Advance care planning from the penultimate hospitalization in patients with end-stage heart failure: a single-center, 10-year experience.

Advance care planning (ACP) is a key element of palliative care even in patients with heart failure (HF); however, the complexity of the clinical trajectory hampers its early introduction. We retrospectively evaluated the state of implementation and the quality of ACP from the penultimate hospitalization in patients with HF who died after repeated hospitalizations. Of the 1117 patients admitted to Saga University Hospital from 2007 to 2016, we excluded 934 patients who survived after discharge or changed hospital, 78 patients who died for a reason other than HF, 42 patients who died during their first HF hospitalization, and 23 patients who died during hospitalization in another hospital. The electronic medical records of the remaining 40 patients were evaluated by three trained physicians on the recently provided 12 recommended elements of ACP, using a 5-point Likert scale (1 = very poor to 5 = excellent). The mean ratings of the 12 ACP elements ranged from 1.0 to 1.9. A do not attempt resuscitation (DNAR) order was issued to 10 patients (25%) just before they died. Of the remaining 30 patients not issued a DNAR order, cardiopulmonary resuscitation was attempted for 23 (76.7%) patients. Among patients with HF who eventually died after repeated hospitalizations, ACP even after the penultimate hospitalization was not evaluated highly. It resulted in a DNAR order in the last few days, a CPR as if their death was sudden and unexpected at the final moment, or CPAOA.

Management of anticoagulant therapy using a portable point-of-care international normalized ratio device and social networking service in a patient with a left ventricular assist device.

Device infection and stroke are still frequently reported as complications of left ventricular assist devices, and strict management of anticoagulation therapy is sometimes difficult at the time of infection status. We report the case of a 55-year-old man with a HeartMate II (Abbott, Inc., Abbott Park, IL, USA) as a bridge to cardiac transplantation. The patient measured his prothrombin time-international normalized ratio (PT-INR) by himself using a point-of-care device at home and reported the result promptly on a social networking service (SNS). Physicians instructed the patient on how to adjust his dose of warfarin based on the result and suggested the next time of measurement on the SNS. Until cardiac transplantation, we adjusted the dose of warfarin 106 times using the SNS because of unexpected PT-INR fluctuations caused by antibiotics. The time in the therapeutic range was maintained at 83.2% without complications, including major bleeding, stroke, or pump replacement; however, there was transient intra-pump thrombosis triggered by severe dehydration due to hyperthyroidism. .

Multidisciplinary Cardiac Rehabilitation and Long-Term Prognosis in Patients With Heart Failure.

BACKGROUND: Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction. METHODS: This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants. RESULTS: Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65-0.92) for composite outcome, 0.67 (95% CI, 0.51-0.87) for all-cause mortality, and 0.82 (95% CI, 0.67-0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients. CONCLUSIONS: Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.

Strategy for estimating optimal heart rate in refractory heart failure with relative sinus bradycardia: A case report.

Relative bradycardia (mild sinus bradycardia) is one of the major barriers for the effective treatment of hemodynamically unstable patients with heart failure and reduced cardiac output. We report a case of a man aged 58 years with an old broad anterior myocardial infarction and relative bradycardia (about 60 bpm) suffering from symptoms of congestive heart failure at rest in spite of optimal medical therapy, including the use of the inotropes. Transvenous atrial pacing during right heart catheterization indicated that an increase in heart rate (up to 80 bpm) improved hemodynamics immediately. Implantation of a pacemaker (atrial pacing of 80 bpm) was effective for stabilizing the heart failure symptoms. Transvenous atrial pacing during right heart catheterization is effective for estimating the optimal heart rate in patients with heart failure and relative bradycardia. .

Nationwide Survey of Multidisciplinary Care and Cardiac Rehabilitation for Patients With Heart Failure in Japan　- An Analysis of the AMED-CHF Study.

BACKGROUND: The purpose of this study was to clarify the implementation rate of multidisciplinary heart failure (HF) care and cardiac rehabilitation (CR) in Japan, as well as the relationship between implementation rates and characteristics of the facility.Methods and Results:Survey participants were cardiologists who are members of the Japan Heart Failure Society and belonged to 1 of 845 medical institutions that are members of the Japan Heart Failure Society, as of April 2016. A total of 288 institutions (34.1%) returned the questionnaire. The percentages of hospitals implementing multidisciplinary HF care were 78.5% for inpatients and 32.6% for outpatients with HF. Inpatient and outpatient CR for HF had implementation rates of 80.4% and 56.5%, respectively. In addition, very few HF patients (7.3%, 3,741/51,323 patients) received outpatient CR. Both the presence of nurses certified in chronic HF care and registered CR instructors on staff were consistently associated with implementation of multidisciplinary HF care, and Japanese Circulation Society training hospitals, lower number of hospital beds, and presence of registered CR instructors on staff were consistently associated with implementation of CR. CONCLUSIONS: This first nationwide survey demonstrated that the implementation rates of multidisciplinary care and CR for HF, especially for outpatients, are low in Japan. Skilled healthcare professionals are expected to play important roles in the widespread implementation of this type of HF care in Japan.

Spontaneous Internal Mammary Artery Graft Dissection Triggered by Emotional Stress.

Internal mammary artery graft dissection is a rare condition and is usually caused by iatrogenic complications or mechanical stress. We experienced a case of acute myocardial infarction due to spontaneous internal mammary artery graft dissection that was triggered by emotional stress and was successfully treated by percutaneous intervention using drug-eluting stents. (Level of Difficulty: Beginner.).

Possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure: a nationwide cross-sectional questionnaire survey.

Palliative care for end-stage heart failure should be provided by a multidisciplinary team. However, the influence of each occupational category on patients receiving palliative care for end-stage heart failure remains unclear. Thus, this study investigated the relationships between palliative care conferences and positive outcomes of palliative care for end-stage heart failure patients. We sent questionnaires to all cardiology training hospitals authorized by the Japanese Circulation Society (n = 1004); of these, responses from the directors at 554 institutions were analyzed. We divided the responding institutions into two groups according to their implementation of palliative care conferences for patients with end-stage heart failure. The institutions that had held such conferences (n = 223) had a larger number of hospital beds, beds in the cardiovascular department, and patients admitted to the cardiovascular department, compared with institutions that had not held these conferences (n = 321). The usage rates of opioids, non-steroidal anti-inflammatory drugs, and sedatives were significantly higher in institutions that held these conferences. Multivariate analysis revealed that nutritionists and medical social workers had greater involvement in the improvement of mental symptoms and ensuring that patients could stay where they wished, respectively. The presence of palliative care physicians, physical therapists, or pharmacists was associated with multiple positive outcomes. This study indicated that there are possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure.

Acute Mitral Regurgitation of Unknown Etiology Associated with Disseminated Intravascular Coagulation Eventually Diagnosed as Enterococcus Faecalis Infective Endocarditis by Mitral Valve Surgery.

BACKGROUND Infective endocarditis is prevalent worldwide and the modified Duke criteria have been used universally to diagnose this condition. However, making the correct diagnosis is rather difficult because the clinical presentation and findings of blood tests are non-specific. CASE REPORT A 70-year-old female complaining of dyspnea for 5 days with acute mitral regurgitation was transferred to our hospital. She had acute heart and respiratory failure and disseminated intravascular coagulation. Although infective endocarditis was suspected, repeated blood cultures and transesophageal echocardiography could not reveal any findings of infective endocarditis. Because the etiology of her condition was not determined by various examinations, mitral annuloplasty was required to treat her mitral regurgitation, and was performed for definitive diagnosis and treatment revealing the presence of vegetation on the mitral valve. Enterococcus faecalis was detected by cultures of the mitral valve and blood after the surgery. CONCLUSIONS It can be very difficult to diagnose infective endocarditis correctly, especially when a case fails to fulfill the modified Duke criteria. In such a case, only cardiac surgery might enable us to make an accurate diagnosis and save a patient's life.

Nationwide Survey of Palliative Care for Patients With Heart Failure in Japan.

BACKGROUND: Palliative care for heart failure (HF) patients is recommended in Western guidelines, so this study aimed to clarify the current status of palliative care for HF patients in Japan.Methods and Results:A survey was sent to all Japanese Circulation Society-authorized cardiology training hospitals (n=1,004) in August 2016. A total of 544 institutions (54%) returned the questionnaire. Of them, 527 (98%) answered that palliative care is necessary for patients with HF. A total of 227 (42%) institutions held a palliative care conference for patients with HF, and 79% of the institutions had <10 cases per year. Drug therapy as palliative care was administered at 403 (76%) institutions; morphine (87%) was most frequently used. Among sedatives, dexmedetomidine (33%) was administered more often than midazolam (29%) or propofol (20%). Regarding the timing of end-of-life care, most institutions (84%) reported having considered palliative care when a patient reached the terminal stage of HF. Most frequently, the reason for the decision at the terminal stage was "difficulty in discontinuing cardiotonics." A major impediment to the delivery of palliative care was "difficulty predicting an accurate prognosis." CONCLUSIONS: This large-scale survey showed the characteristics of palliative care for HF in Japan. The present findings may aid in the development of effective end-of-life care systems.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Design of a nationwide survey on palliative care for end-stage heart failure in Japan.

BACKGROUND: The term palliative care has historically been associated with support for individuals with advanced incurable cancer, so cardiologists and cardiac nurses may be unfamiliar with its principles and practice. However, palliative care is now a part of end-stage heart failure management. We conducted the first nationwide survey to investigate the status of palliative care for heart failure in Japan. METHODS AND RESULTS: A self-reported questionnaire was mailed to all Japanese Circulation Society - authorized cardiology training hospitals (n=1004) in August 2016. The response deadline was December 2016. The survey focused on the following topics: basic information about the facility and multidisciplinary team, patient symptoms for palliative care, positive outcomes after providing palliative care, drug therapy as palliative care for patients with heart failure, advance care planning with patients and their families, and impediments to providing palliative care to patients with heart failure. The results of the survey will be reported in detail elsewhere. CONCLUSIONS: Current guidelines on palliative care do not specifically address what team members should be involved, what drugs should be used, or when palliative care should be started. This survey collected information to improve the quality of palliative care and provide more specialized palliative care within the limits of resources.

Myeloid-related protein-8/14 in acute coronary syndrome.

BACKGROUND: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). METHODS AND RESULTS: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R2=0.52), but not with soluble P-selectin level (R2=0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression. CONCLUSIONS: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS.

N-terminal pro-brain natriuretic peptide and associated factors in the general working population: a baseline survey of the Uranosaki cohort study.

Few data on clinical characteristics associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) or the clinical value of measuring NT-proBNP in the working population are available. The aim of the present study was to investigate the levels of NT-proBNP and their association with clinical variables in the Japanese general working population by using baseline data from the Uranosaki cohort study. In the study, the plasma concentration of NT-proBNP and some biomarkers were measured in addition to the standard health checkups at the workplace. Questionnaires regarding health-related quality of life (HR-QOL) were also completed. A total of 2140 participants were enrolled in the study. Plasma levels of NT-proBNP were positively associated with age, female sex, systolic blood pressure, pulse pressure, prevalent hypertension, smoking habit, high-density lipoprotein cholesterol (HDL-C), and prevalent proteinuria, and negatively associated with body mass index, lipid profiles except HDL-C, uric acid, renal function, and hemoglobin. Both the plasma concentration of high-molecular weight adiponectin and that of high-sensitivity troponin T were positively and independently associated with NT-proBNP. In addition, the HR-QOL score regarding sleep disorder was independently associated with NT-proBNP. Thus, we have obtained evidence that the plasma NT-proBNP is affected by several clinical variables in the general working population.

Validity and Reliability of Three-chamber-View Three-directional Encoded Phase-contrast Magnetic Resonance Velocity-Vector Mapping for Transmitral Velocity Measurements: Comparison with Doppler Echocardiography and Intra- and Inter-observer Variability.

PURPOSE: Three-chamber view (3ch.) three-directional encoded phase-contrast magnetic resonance velocity vector mapping (PCMRVM) has been used for visualization and assessment of intra-cardiac flow. Although transmitral inflow velocity can be determined using this method by tracing mitral tips during the cardiac phase, its feasibility for clinical applications has not been established. Our aim was to investigate the validity and reproducibility of 3ch. PCMRVM for determining transmitral inflow velocity. METHODS: We conducted 3ch. PCMRVM for 32 patients and eight healthy volunteers and analyzed the transmitral inflow pattern and early (E) and late (A) diastolic velocity. Nine patients also underwent Doppler echocardiography to evaluate correlations between the methods for E and A velocities and the E/A ratio. Intra- and inter-observer variability were calculated using intraclass correlation coefficients (ICC [1, 1] and ICC [2, 1]) for peak E and A velocities, Spearman's rank correlation coefficient for the E/A ratio, and Cohen's kappa coefficient for the inflow pattern. RESULTS: Bland-Altman plots indicated that 3ch. PCMRVM showed systemically lower velocities than Doppler echocardiography for E (3 [25.8] 48.6) and A (-6.28 [21] 48.3); however, a strong correlation was observed (r = 0.81, P < 0.0001). The E/A ratio was not statistically different between the two modalities (P = 0.21). The intra- and inter-observer variabilities for peak E and A velocities and the E/A ratio demonstrated nearly perfect agreement or strong correlations, except for the peak E velocity (ICC [2, 1] = 0.751). CONCLUSION: Based on these results, 3ch. PCMRVM can be used for both visualization and assessment of intra-cardiac flow and evaluation of the transmitral inflow velocity.

Pentraxin-3 regulates the inflammatory activity of macrophages.

BACKGROUND AND AIMS: Pentraxin-3 (PTX3) reportedly has protective roles in atherosclerosis and myocardial infarction, and is a useful biomarker of vascular inflammation. However, the detailed functions of PTX3 in inflammation are yet to be elucidated. This study aimed to investigate the function of PTX3 in macrophages. METHODS: PMA-treated THP-1 cell line (THP-1 macrophage) and monocyte-derived human primary macrophages were treated with recombinant PTX3. Cytokine and chemokine levels in the THP-1 culture medium were measured as well as monocyte chemoattractant protein (MCP-1) concentrations in the Raw 264.7 cell culture medium. PTX3-silenced apoptotic macrophages (THP-1 cell line) were generated to investigate the roles of PTX3 in phagocytosis. RESULTS: In the presence of PTX3, macrophage interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and MCP-1 levels were reduced significantly (-39%, P=0.007; -21%, P=0.008; and -67%, P=0.0003, respectively), whilst activated transforming growth factor-ß (TGF-ß) was detected in the THP-1 macrophages (P=0.0004). Additionally, PTX3 induced Akt phosphorylation and reduced nuclear factor-kappa B (NF-κB) activation by 35% (P=0.002), which was induced by TNF-α in THP-1 macrophages. Furthermore, silencing of PTX3 in apoptotic cells resulted in increased macrophage binding, elevated expression rate of HLA-DR (+30%, P=0.015) and CD86 (+204%, P=0.004) positive cells, and induction of IL-1ß (+36%, P=0.024) production. Conversely, adding recombinant PTX3 to macrophages reduced CD86 and HLA-DR expression in a dose-dependent manner. CONCLUSIONS: We identified PTX3 as a novel regulator of macrophage activity, and this function suggests that PTX3 acts to resolve inflammation.