Quantitative Evaluation of Right Ventricular Workload Based on the Stroke Work Index in Patients after Right Ventricular Outflow Tract Reconstruction.

The evaluation of right ventricular workload is sometimes complicated in patients after right ventricular outflow tract reconstruction (RVOTR) because both stenotic and regurgitation lesions are involved. In this study, we modified the right ventricular stroke work index (RVSWI) and evaluated the relationship between the modified RVSWI (mRVSWI) and patient prognosis after RVOTR.We enrolled 69 patients who underwent RVOTR (the RVOTR group), including those who needed early reoperation (early reoperation subgroup) and those who did not (follow-up subgroup), and 13 age-matched control participants (control group). Based on the catheterization results 1 year after RVOTR, we compared the mRVSWI between these groups. Additionally, we evaluated the influence of the mRVSWI on the reoperation avoidance rate and survival.The mRVSWI in the RVOTR group was significantly greater than that in the control group (17.7 ± 8.6 vs. 11.0 ± 2.7 g·m/m2, p = 0.008). The mRVSWI in the early reoperation subgroup was significantly greater than that in the follow-up subgroup (32.5 ± 11.1 vs. 15.8 ± 6.0 g·m/m2, p < 0.0001). In the follow-up subgroup, patients with an mRVSWI higher than the upper limit of normal (16.4 g·m/m2) had a greater rate of reoperation than did the other patients (p = 0.0013). One patient died suddenly, and her mRVSWI was consistently high throughout her life.We established the mRVSWI as an index that integrates the pressure and volume load on the right ventricle. Our results indicate the utility of the mRVSWI for predicting patient prognosis after RVOTR.

Predictive role of regional thigh tissue oxygen saturation monitoring during cardiopulmonary bypass in lung injury after cardiac surgery.

Acute respiratory distress syndrome (ARDS) is a serious complication following cardiac surgery mainly associated with the use of cardiopulmonary bypass (CPB), which could increase the risk of mortality and morbidity. This study investigated the association of regional oxygen saturation (rSO2) during CPB with postoperative outcomes, including respiratory function. Patients who underwent cardiac surgery with CPB from 2015 to 2019 were included. Near-infrared spectroscopy was used to monitor rSO2 at the forehead, abdomen, and thighs throughout the surgery. Postoperative markers associated with CPB were assessed for correlations with PaO2/FiO2 (P/F) ratios at intensive care unit (ICU) admission. Postoperative lung injury (LI) was defined as moderate or severe ARDS based on the Berlin criteria, and its incidence was 29.9% (20/67). On multiple regression analysis, the following were associated with P/F ratios at ICU admission: vasoactive-inotropic scores at CPB induction (P = 0.03), thigh rSO2 values during CPB (P = 0.04), and body surface area (P < 0.001). A thigh rSO2 of 71% during CPB was significantly predictive of postoperative LI with an area under the curve of 0.71 (P = 0.03), sensitivity of 0.70, and specificity of 0.68. Patients with postoperative LI had longer ventilation time and ICU stays. Thigh rSO2 values during CPB were a potential predictor of postoperative pulmonary outcomes.

Recurrent left ventricular thrombus due to essential thrombocythemia complicated by COVID-19.

Essential thrombocythemia is a risk factor for thrombosis and hemorrhage. During the perioperative period of cardiac surgery, the risk of thrombosis and hemorrhage increases. Coronavirus disease 2019 (COVID-19) is also associated with thrombosis. We present the case of a 69-year-old man with essential thrombocythemia complicated by COVID-19 who developed a left ventricular thrombus. We performed thrombectomy, but the patient developed recurrent left ventricular thrombus 8 days after surgery. Emergency redo thrombectomy was performed followed by aggressive blood-thinning therapy. The postoperative course was complicated by cardiac tamponade requiring surgical drainage 8 days after the second surgery. The patient was discharged home 25 days after the second operation without any complications. Learning objective: Left ventricular thrombus is a rare but fatal complication associated with essential thrombocythemia. COVID-19 has also been reported to cause coagulopathy. This case suggested that after surgery for left ventricular thrombus complicated by multiple risk factors including essential thrombocythemia and COVID-19, aggressive blood-thinning therapy with combination of anticoagulation, antiplatelet, and metabolic antagonist may help prevent recurrent thrombosis.

Initial thickness of the crescent may not be a reliable predictor of complications in type A intramural haematoma.

OBJECTIVES: This study aimed to investigate changes in haematoma thickness during the early period and their association with disease progression in patients who received initial medical treatment for type A intramural haematoma (IMH). METHODS: Medical records and serial computed tomography angiography (CTA) images of patients who did not undergo emergency aortic repair for type A IMH upon presentation were retrospectively reviewed. The haematoma remodelling rate was determined using the following equation: thickness of the haematoma on the first CTA (mm) - thickness of the haematoma on the second CTA (mm)time between the first and second CTAs (h). RESULTS: Among the 40 patients included in this study, 38 were indicated for initial watch-and-wait strategy, whereas 2 were indicated for emergency aortic repair but declined it. During hospitalization, 10 patients developed disease progression, with 2 in-hospital mortality cases. Analysis of the haematoma remodelling rate in 39 patients revealed that such a rate was significantly associated with the reciprocal of the time from onset. Analysis of all 70 CTA examinations performed within 24 h after the onset of IMH showed that haematoma thickness was significantly associated with the logarithm of the time from onset. Initial regression of the haematoma was not necessarily associated with avoidance of disease progression. CONCLUSIONS: In type A IMH, the thickness of the haematoma in the ascending aorta tended to decrease in the very early period; however, prompt regression of the haematoma was not necessarily associated with avoidance of disease progression.

Upper partial sternal split for pediatric cardiac surgery.

OBJECTIVES: We introduced the use of an upper partial sternal split for pediatric cardiac surgical procedures in our unit in 2016. We report the outcomes of our experience in 51 patients using this approach. METHODS: From February 2016 to September 2022, 51 patients underwent congenital cardiac surgical procedures using an upper partial sternal split including vascular ring repair (n = 20), subaortic membrane (n = 12), ventricular septal defect closure with aortic valve resuspension (n = 9), aortic arch repair (n = 4), pulmonary artery band (n = 2), pulmonary artery sling (n = 1), supravalvular aortic stenosis (n = 1), aortic valve replacement (n = 1), and pulmonary artery plasty (n = 1). The surgical approach involved a midline skin incision, based on the manubrium, followed by an upper manubriotomy. No special surgical instrumentation was required. Median patient age was 2.9 years (IQR 1.3, 6.0); median body weight was 15 kg (IQR 9.8, 20). RESULTS: There was no mortality and no patient required intraoperative conversion to full sternotomy. One patient required re-exploration for bleeding when the incision was converted to a full sternotomy. There were no wound complications in any patient. Twenty-one patients (41%) were extubated on the table and of the remaining 30 patients, 23 patients (76%) were extubated within 24 h of surgery. Eleven patients did not require intensive care unit (ICU) admission. Median ICU and hospital stay was 1 day (IQR 1, 1.25) and 5 days (IQR 4, 8) ,respectively. CONCLUSION: An upper partial sternal split approach is straightforward and can be performed safely with a preferable cosmetic result in selected pediatric cardiac operations.

Thrombocytopenia Following Perceval Sutureless Aortic Valve Replacement in Asian Patients.

BACKGROUND: This study analyzed the safety and performance of the Perceval valve for aortic valve replacement (AVR) in patients at 1 year after undergoing aortic stenosis (AS) treatment, and its effect on significant declines in the platelet count during the immediate postoperative period.Methods and Results: Data were collected retrospectively for the initial 121 patients (median age 77 years; 47.1% females) who underwent Perceval sutureless AVR between May 2019 and July 2022. Implantation was successful in all (100%), with median cross-clamp and CPB times of 59 and 100 min, respectively. Postoperative thrombocytopenia (platelet count <50×103/µL) was noted in 80 (66.1%) patients. Multivariate analysis showed advanced age (>80 years), preoperative low platelet count (<200×103/µL), and a sternotomy approach as significant risk factors for postoperative thrombocytopenia. One (0.8%) patient died within 30 days after the procedure. The 2-year site-reported event rate was 14% (n=17) for all-cause mortality, 0.8% (n=1) for cardiac mortality, 4.1% (n=5) for stroke, and 1.7% (n=2) for endocarditis and valve-related reoperation; there were no instances of paravalvular leakage or structural valve deterioration. CONCLUSIONS: Thrombocytopenia was common after Perceval sutureless AVR, although its impact was not significant. Although Perceval sutureless AVR was found to be a safe and effective option, preoperative assessment of potential bleeding should be performed and the Perceval valve should not be used for patients with a high bleeding risk.

Watch-and-wait strategy for selected patients with type A intramural hematoma.

OBJECTIVE: This single-center retrospective study evaluated early and midterm outcomes of 100 consecutive patients with type A intramural hematoma. METHODS: Initial watch-and-wait strategy was indicated if the maximum aortic diameter was < 50 mm, pain score was < 3/10 on the numerical rating scale, and no ulcer-like projection was observed in the ascending aorta. The primary endpoints of this study were all-cause and aorta-related deaths, and the secondary endpoint was aortic events. RESULTS: Initial watch-and-wait strategy was indicated in 52 patients. Emergency aortic repair was indicated in the remaining 48 patients; 2, 31, and 15 patients died before surgery, underwent emergency surgery, and declined emergency surgery, respectively. Among the watch-and-wait group, 11 (21%) patients underwent aortic repair during hospitalization. In-hospital mortality rates, 5-year survival rates, and 5-year freedom from aorta-related death were not significantly different between the initial watch-and-wait strategy and emergency surgery (2% vs. 6%, 92% vs. 82%, and 100% vs. 94%, respectively). In the initial watch-and-wait strategy group, 5-year freedom from aortic events and freedom from aortic events involving the ascending aorta were 60% and 66%, respectively. CONCLUSIONS: The early and midterm outcomes with the initial watch-and-wait strategy in patients with type A intramural hematoma with a maximum aortic diameter of ≤ 50 mm, pain score of ≤ 3/10, and no ulcer-like projection in the ascending aorta were favorable with no aorta-related death.

Successful treatment of fulminant myocarditis due to COVID-19 in a 5-year-old girl.

Reports of acute myocarditis are increasing due to the worldwide spread of coronavirus disease 2019 (COVID-19). We report a case of a 5-year-old girl with fulminant myocarditis caused by COVID-19, who was successfully treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The unvaccinated patient had developed fever 1 week before attending our hospital and was "presumptive positive" for COVID-19 based on the surrounding infectious situation. The fever resolved, but the day before the visit, abdominal pain appeared. The patient visited her previous physician with vomiting as the main complaint. She was transferred to our hospital due to impaired consciousness and bradycardia, with a heart rate of 40 beats/min. Immediately after transfer, she was diagnosed with complete atrioventricular (AV) block and was scheduled to undergo percutaneous pacing lead insertion. However, the patient had ventricular tachycardia, AV block and hypotension intraoperatively and required cardiopulmonary resuscitation. The patient was in an extremely unstable circulatory state, and VA-ECMO was urgently introduced. After multidisciplinary treatment for acute myocarditis, waiting for an improvement in AV block, and recovery of cardiac function, the patient was weaned from VA-ECMO on the eighth day after admission. The patient was discharged with no cardiac or neurologic sequelae. Learning objective: The rapid introduction of veno-arterial extracorporeal membrane oxygenation for fulminant myocarditis caused by coronavirus disease 2019 (COVID-19) in young children is extremely effective. Vaccination may be important for preventing infection with COVID-19 and avoiding severe complications.

Coil-in-Plug Method for Left Subclavian Artery Embolization in Thoracic Endovascular Aortic Repair with Arch Vessel Debranching.

Objectives: Since 2018, we have routinely placed an Amplatzer vascular plug (AVP) in the proximal left subclavian artery (LSCA) to prevent embolic events during thoracic endovascular aortic repair with arch vessel debranching (d-TEVAR). Type II endoleaks of LSCA origin were observed in two patients (20%), and the coil-in-plug (CIP) method, i.e., microcatheter insertion through the plug and addition of coil embolization, which has been used since August 2019, was performed. This study aims to evaluate the effectiveness of the CIP method for LSCA embolization. Methods: A total of 26 patients who underwent d-TEVAR for an aortic arch aneurysm between 2018 and 2022 were retrospectively reviewed. Ten patients who underwent d-TEVAR with a simple AVP placement (the control group) and 16 patients who underwent d-TEVAR with the CIP method (the CIP group) were compared. Results: Two patients had type II endoleaks in the control group, whereas none had them in the CIP group. LSCA length was significantly shorter in patients with endoleaks than in those without endoleaks (24.5 vs. 50.3 mm; p<0.01). No perioperative deaths or cerebral infarctions occurred in either group. Conclusions: AVP placement in the LSCA during d-TEVAR effectively prevented perioperative cerebral infarction. d-TEVAR with CIP was especially useful in patients with a short LSCA.

Bioprosthetic Valve Deterioration: Accumulation of Circulating Proteins and Macrophages in the Valve Interstitium.

Histologic evaluations revealed excessive accumulations of macrophages and absence of fibroblastic interstitial cells in explanted bioprosthetic valves. Comprehensive gene and protein expression analysis and histology unveiled an accumulation of fibrinogen and plasminogen, an activator of infiltrated macrophages, from degenerated valve surfaces in the interstitial spaces. These pathologies were completely reproduced in a goat model replaced with an autologous pericardium-derived aortic valve. Further preclinical animal experiments using goats demonstrated that preventing infiltration of macrophages and circulating proteins by increasing collagen density and leaflet strength is an effective treatment option.

Long-term outcomes of hypoplastic left heart syndrome with analysis of the Norwood procedure in infants following bilateral pulmonary artery banding.

Objective: To investigate the early and long-term outcomes of the deferred Norwood procedure by bilateral pulmonary artery banding (BPAB) versus the neonatal Norwood procedure. Methods: This retrospective study examined 46 patients with hypoplastic left heart syndrome and its variants undergoing the Norwood procedure for single ventricle physiology between 2004 and 2022 at 3 institutions. The patients were divided into 2 groups: neonatal Norwood procedure (group N; n = 23) and staged Norwood procedure in infants following BPAB (group I; n = 23). Preoperative risk factors, surgical results, survival rates, Fontan candidacy, and long-term complications were compared. Results: Early survival rates after the Norwood procedure were 91.3% (21 of 23) in both groups. Late survival rates after the Norwood procedure were similar at the 10-year follow-up (group N, 76.3%; group I, 68.7%; P = .63). Fontan completion rates also were comparable in the 2 groups (group N, 77.8%; group I, 85.7%; P = .67). Group N showed a higher median pulmonary artery (PA) index before bidirectional cavopulmonary connection (group N, 177 [interquartile range (IQR), 147-243] mm2/m2; group I, 152 [IQR, 146-163] mm2/m2; P = .03); this trend continued until 5 years after Fontan completion (P = .01). Group N also had a lower rate of freedom from protein-losing enteropathy (PLE) at 9.0 years after the Fontan operation (90.0% vs 52.5% for group I; P = .04), although the incidences of other Fontan-associated events were not significantly different. Conclusions: Fontan candidacy and survival rates were similar regardless of the timing of the Norwood procedure. Early performance of the Norwood procedure may lead to lower rates of late Fontan-associated events, such as PLE.

Acute Kidney Injury after High-Flow Regional Cerebral Perfusion in Neonatal and Infant Aortic Arch Repair.

OBJECTIVES: We applied high-flow regional cerebral perfusion (HFRCP) for aortic arch reconstruction in neonates and infants by monitoring regional oxygen saturation of the thigh (rSO2T) using near-infrared spectroscopy to maintain peripheral perfusion. This study was designed to investigate the optimal perfusion flow of HFRCP for renal protection. METHODS: From 2009 to 2021, 28 consecutive neonates and infants who underwent aortic arch reconstruction with HFRCP were enrolled. The median age of the patients was 27 days; the median body weight was 3.0 kg. In HFRCP, perfusion flow was targeted at approximately 80-100 mL/kg/min and then lowered corresponding to brain rSO2 levels and blood gas data. Isosorbide dinitrate and chlorpromazine were administered to enhance peripheral perfusion flow. Regional oxygen saturation of the forehead and thighs were monitored. The stage of acute kidney injury (AKI) was classified based on the Kidney Disease Improving Global Outcomes criteria. RESULTS: No patients had neurological events and peritoneal dialysis after surgery. The incidence of AKI was 39.3% with only three patients having greater than stage 2 AKI. The maximum postoperative serum creatinine concentration was negatively associated with the lowest rSO2T during HFRCP. The rSO2T during HFRCP was a predictive factor for postoperative creatinine increase of ≧0.3 mg/dL. The area under receiver operating characteristic curve was 0.78 with the cutoff value of 48% for rSO2T. CONCLUSIONS: The rSO2T during HFRCP is a potential predictor of postoperative renal function. To prevent AKI, the rSO2T should be preserved more than 48% by increasing HFRCP flow.

Monitoring of intraoperative femoral oxygenation predicts acute kidney injury after pediatric cardiac surgery.

Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a pediatric cardiac surgery postoperative complication that is associated with a longer duration of mechanical ventilation and length of hospital stay. Identifying an early predictor of CPB-AKI is critical. Near infrared spectroscopy (NIRS), which can provide real-time monitoring of regional tissue oxygen saturation (rSO2) during CPB, may predict CPB-AKI in an early phase of surgical treatment. This study analyzed clinical data from 87 children who underwent an elective surgical repair of ventricular septal defect (VSD) from January 2013 to March 2019. NIRS sensors were placed on the patients' forehead, abdomen, and thighs. The pediatric modified risk, injury, failure, loss, and end-stage (p-RIFLE) score was determined for each patient postoperatively. The incidence of AKI based on the p-RIFLE classification was 11.5% at the end of surgery, 23.0% at 24 h after surgery, and 5.7% at 48 h after surgery. The AKI incidence rate was highest at 24 h after surgery. Multiple regression analysis revealed that femoral oxygenation (rSO2) during CPB, CPB time, oxygen delivery index (DO2i), and lactate at the end of CPB were independent risk factors for AKI. Receiver-operating characteristic curve analysis indicated that femoral oxygenation of 74% or less predicted AKI development within 24 h after surgery. In conclusion, rSO2 measured at the thigh during CPB is highly predictive of CPB-AKI.

Conversion of Norwood-Rastelli Procedure to "Anatomic" Biventricular Circulation With Takedown of Aortopulmonary Amalgamation After Aortic Valve Growth.

The pathways for biventricular repair of hypoplastic aortic arch with ventricular septal defect, small aortic valve, and normal-sized left ventricle vary depending on the disease spectrum. We report a case of an infant who underwent a staged Norwood-Rastelli procedure for aortic stenosis (bicuspid aortic valve), hypoplastic aortic arch, and coarctation of the aorta with ventricular septal defect and normal-sized left ventricle. Ten years after the initial surgery, normal circulatory physiology was achieved with a takedown of the aortopulmonary amalgamation and VSD closure. This became possible as a result of the growth of the aortic valve and annulus. We suggest that this may have been related to progressive narrowing of the surgically created pathway by which some of the left ventricular outflow had been routed through the ventricular septal defect to the native pulmonary valve.

A single-centre, retrospective study of mid-term outcomes of aortic arch repair using a standardized resection and patch augmentation technique.

OBJECTIVES: The aim of this study was to evaluate the mid-term outcomes after the repair of aortic arch using a standard patch augmentation technique. METHODS: The study included all patients who underwent repair of a hypoplastic/interrupted aortic arch (IAA) in a single institute from June 2012 to December 2019 by a standardized patch augmentation (irrespective of concomitant intra-cardiac lesions). End points evaluated were reintervention for arch obstruction and persistent/new-onset hypertension. RESULTS: The study included 149 patients [hypoplastic aortic arch, n = 92 (62%), IAA, n = 9 (6%), Norwood procedure, n = 48 (32%)]. The patch material used for augmentation of the aortic arch included pulmonary homograft (n = 120, 81%), homograft pericardium (n = 18, 12%), CardioCel® (n = 9, 6%) and glutaraldehyde-treated autologous pericardium (n = 2, 1%). The median age and weight at surgery were 7 days [interquartile range (IQR) 5-17 days] and 3.5 kg (IQR 3-3.9 kg), respectively. The median follow-up was 3.27 years (IQR 1.28, 5.08), range (0.02, 8.76). Freedom from reintervention at 1, 3 and 5 years was 95% [95% confidence interval (CI) = 89%, 98%], 93% (95% CI = 86%, 96%) and 93% (95% CI = 86%, 96%) respectively. One patient (0.6%) had persistent hypertension 8 years after correction for interrupted arch with truncus arteriosus. CONCLUSIONS: Repair of hypoplastic/IAA by transection and excision of all ductal tissue and standardized patch augmentation provide good mid-term durability. The freedom from reintervention at 5 years is >90%. The incidence of persistent systemic hypertension following arch reconstruction is low. The technique is reproducible and applicable irrespective of underlying arch anatomy.

Outcomes after Rivaroxaban Treatment of Extensive Deep Vein Thrombosis.

BACKGROUND: Regression of thrombus in response to treatment with direct oral anticoagulants (DOACs) in patients with extensive deep vein thrombosis (DVT) has not been fully evaluated. This study aimed to determine the therapeutic efficacy of rivaroxaban in the treatment of extensive DVT. METHODS: We retrospectively evaluated 76 patients treated with rivaroxaban among 728 new DVT patients, at our hospital from January 2018 to March 2021. Extensive DVT was defined as thrombus connecting to 2 or more segments of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. Localized DVT was defined as a thrombus confined to 1 segment of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. We compared the changes in thrombus between the extensive DVT group (36 patients) and the localized DVT group (40 patients). RESULTS: In the localized DVT group, 14 (37%) had total recanalization within 3 weeks after DOAC initiation, and 30 (79%) had total recanalization within 3 months. In the extensive DVT group, only 3 (9%) had total recanalization within 3 weeks after starting DOAC, and even after 3 months, only 5 (15%) had total recanalization. Symptoms (P = 0.01) and extensive DVT (P < 0.01) were significantly associated with the risk for failure of total recanalization. CONCLUSIONS: Rivaroxaban was highly effective for total recanalization of localized DVT but not for symptomatic or extensive DVT. In patients with symptomatic extensive DVT, catheter-based thrombolysis may be considered in selected cases.

Regional oxygen saturation change rate for detection of leg ischemia in minimally invasive cardiac surgery.

INTRODUCTION: The criteria for placement of distal perfusion cannulas vary among reports. This cohort study aimed to establish a reproducible method to monitor critical leg ischemia during minimally invasive cardiac surgery. METHODS: We included 121 patients who underwent minimally invasive cardiac surgery via right thoracotomy with right femoral arterial cannulation from 2015 to 2018. The change rate of regional oxygen saturation (ΔrSO2) was calculated as follows: rSO2 (baseline) - rSO2 (actual number)/rSO2 (baseline). Patients were divided into Group N (ΔrSO2 < 40%): 100/121 (83%) and Group H (ΔrSO2 > 40%, <10 minutes if >40%): 21/121 (17%). A distal perfusion cannula was placed when ΔrSO2 was >40% over 10 minutes. RESULTS: No patients experienced significant leg ischemia. Significantly longer cardiopulmonary bypass and aortic cross-clamp times were observed in Group H than in Group N (cardiopulmonary bypass time, 129 ± 36 minutes (Group N) vs. 151 ± 34 minutes (Group H), p = 0.01). ΔrSO2 correlated positively with plasma creatine phosphokinase elevation (R = 0.40, p < 0.001) on postoperative day 1. Serum lactate on intensive care unit admission showed a significant positive correlation (R = 0.40, p < 0.001) with ΔrSO2. CONCLUSION: ΔrSO2 measurement by near-infrared spectroscopy can facilitate distal leg perfusion monitoring and assist surgeons in preventing critical leg ischemia during minimally invasive cardiac surgery.

Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation.

OBJECTIVES: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. METHODS AND RESULTS: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-ß/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-ß/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. CONCLUSIONS: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.