Tet1 regulates epigenetic remodeling of the pericentromeric heterochromatin and chromocenter organization in DNA hypomethylated cells.

Pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions, plays crucial roles in various cellular events, such as cell division and DNA replication. PCH forms chromocenters in the interphase nucleus, and chromocenters cluster at the prophase of meiosis. Chromocenter clustering has been reported to be critical for the appropriate progression of meiosis. However, the molecular mechanisms underlying chromocenter clustering remain elusive. In this study, we found that global DNA hypomethylation, 5hmC enrichment in PCH, and chromocenter clustering of Dnmt1-KO ESCs were similar to those of the female meiotic germ cells. Tet1 is essential for the deposition of 5hmC and facultative histone marks of H3K27me3 and H2AK119ub at PCH, as well as chromocenter clustering. RING1B, one of the core components of PRC1, is recruited to PCH by TET1, and PRC1 plays a critical role in chromocenter clustering. In addition, the rearrangement of the chromocenter under DNA hypomethylated condition was mediated by liquid-liquid phase separation. Thus, we demonstrated a novel role of Tet1 in chromocenter rearrangement in DNA hypomethylated cells.

Association of collateral flow with clinical outcomes in patients with acute myocardial infarction.

Coronary collateral flow is an important prognostic marker in percutaneous coronary intervention (PCI) for chronic total occlusion. However, the role of collateral flow to the culprit lesion of acute myocardial infarction (AMI) has not been fully established yet. The purpose of this retrospective study was to examine the association between collateral flow and long-term clinical outcomes in patients with AMI. We included 937 patients with AMI, and divided those into the no-collateral group (n = 704) and the collateral group (n = 233) according to the presence or absence of collateral flow to the culprit lesion of AMI. The primary endpoint was the incidence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, non-fatal MI, re-admission for heart failure, and ischemia driven target vessel revascularization. The median follow-up duration was 473 days (Q1: 184 days- Q3: 1027 days), and a total of 263 MACE was observed during the study period. The incidence of MACE was significantly greater in the no-collateral group than in the collateral group (29.8% vs. 22.3%, p = 0.027). In the multivariate COX hazard model, the presence of collateral flow was inversely associated with MACE (HR 0.636, 95% CI 0.461-0.878, p = 0.006) after controlling multiple confounding factors. In conclusion, the presence of collateral flow to the culprit lesion of AMI was inversely associated with long-term adverse outcomes. Careful observation of collateral flow may be important in emergent coronary angiography to stratify a high-risk group among various patients with AMI.

Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models.

Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disorder and is sometimes associated with frontotemporal dementia. Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited peripheral neuropathies causing the slow progression of sensory and distal muscle defects. Of note, the severity and progression of CMT symptoms markedly vary. The phenotypic heterogeneity of ALS and CMT suggests the existence of modifiers that determine disease characteristics. Epigenetic regulation of biological functions via gene expression without alterations in the DNA sequence may be an important factor. The methylation of DNA, noncoding RNA, and post-translational modification of histones are the major epigenetic mechanisms. Currently, Drosophila is emerging as a useful ALS and CMT model. In this review, we summarize recent studies linking ALS and CMT to epigenetic regulation with a strong emphasis on approaches using Drosophila models.

Clinical Factors Associated with Long Fluoroscopy Time in Percutaneous Coronary Interventions to the Culprit Lesion of Non-ST-Segment Elevation Myocardial Infarction.

The clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) were comparable or even worse than those with ST-segment elevation myocardial infarction (STEMI). Although successful percutaneous coronary intervention (PCI) to the culprit lesions of NSTEMI would improve the clinical outcomes, some PCI require long fluoroscopy time, reflecting the difficulty of PCI. This study aims to find clinical factors associated with long fluoroscopy time in PCI to the culprit lesion of NSTEMI. We included 374 patients and divided those into the conventional fluoroscopy time (n = 302) and long fluoroscopy time (n = 72) groups according to the quintiles of fluoroscopy time. Clinical and angiographic parameters were compared between the two groups. Calcification and tortuosity were significantly more severe in the long fluoroscopy time group than in the conventional fluoroscopy time group. The prevalence of previous coronary artery bypass grafting (CABG) and bifurcation lesions was significantly greater in the long fluoroscopy time group than in the conventional fluoroscopy time group. In the multivariate stepwise logistic regression analysis, previous CABG (odds ratio [OR], 3.368; 95% confidence interval [CI], 1.407-8.064; P = 0.006), bifurcation lesion (OR, 2.407; 95% CI, 1.285-4.506; P = 0.006), excessive tortuosity (versus mild to moderate tortuosity; OR, 4.095; 95% CI, 1.159-14.476; P = 0.029), and moderate to severe calcification (versus none to mild; OR, 5.792; 95% CI, 3.254-10.310; P < 0.001) were significantly associated with long fluoroscopy time. In conclusion, previous CABG, bifurcation, excessive tortuosity, and moderate to severe calcification were associated with long fluoroscopy time. Our study provided a reference for PCI operators to identify the difficulties in PCI to the culprit lesion of NSTEMI.

[Risk Analysis of Acute Kidney Injury after Cardiac Surgery and Protective Effect by Less Invasive Surgery].

OBJECTIVE: We aimed to determine the incidence and risk of acute kidney injury (AKI) in patients after cardiac surgery, and to assess the effects of less invasive cardiac surgery on the prevention of postoperative AKI. METHODS: We retrospectively analyzed perioperative parameters in patients who underwent cardiac surgery. Risk factors for AKI were determined using univariate and multiple logistic regression models. The incidence of postoperative AKI was also compared between conventional and minimally invasive cardiac surgeries. RESULTS: Among 126 patients, 36 (28.6%) who developed postoperative AKI stayed significantly longer in the intensive care unit(ICU), required prolonged postoperative ventilation and had a higher frequency of renal replacement therapy. Multivariate analysis revealed cardio-pulmonary bypass (CPB) duration and red blood cell transfusion as independent risk factors for postoperative AKI. The incidence of postoperative AKI was significantly lower after off-pump coronary artery bypass grafting than conventional coronary artery bypass grafting (CABG)(0% versus 11%, p=0.025), and after minimally invasive cardiac surgery compared with conventional valve surgery( 4% versus 44%, p=0.01) Conclusion:The duration of CPB and red blood cell transfusion were considered independent factors for the development of postoperative AKI. Less invasive cardiac surgeries might protect against postoperative AKI.

[The treatment strategy for hypoplastic left heart syndrome].

In the recent years, the outcomes of treatment for hypoplastic left heart syndrome (HLHS) is improved because of perioperative management and procedure. We adopt a strategy of the primary Norwood procedure basically for neonates with HLHS, however bilateral pulmonary artery banding precede in patients with risk factors. In the Norwood procedure, aortic arch is reconstructed without artificial prostheses and pulmonary blood flow is supplied from the Blalock-Taussig shunt or the right ventricle-pulmonary artery shunt by case. We administer high dose vasodilators and nitric oxide gas with low resistance strategy after the Norwood procedure. The survival rate of patients with HLHS after 2005 is 84.2% in this strategy.

Risk factor analysis for aortic dissection after aortic valve replacement in patients with tricuspid aortic valve.

OBJECTIVE: Aortic dilatation concurrent with aortic valve disease is a common condition. However, the incidence of aortic dissection after aortic valve replacement for tricuspid aortic valve has not been fully investigated. Therefore, we performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. METHODS: We retrospectively reviewed 599 patients who underwent aortic valve replacement at our hospital between January 2000 and December 2020. We performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. RESULTS: Seven patients developed late aortic dissections during the follow-up period. All patients with aortic dissection underwent aortic valve replacement for aortic regurgitation. Multivariable analysis revealed that aortic regurgitation was an independent predictor of aortic dissection (p < 0.0001). The mean ascending aortic diameter at aortic valve replacement for aortic regurgitation was significantly greater in patients with aortic dissection than in those without aortic dissection (46 [43.5-46] mm vs. 39 [36-42] mm, p < 0.001). The predictive cutoff value of ascending aortic diameter was indicated using receiver operating characteristic curve analysis; 46.0 mm (area under the curve: 0.8987). Freedom rates from aortic dissection in patients with aortic regurgitation and an ascending aortic diameter ≥ 46 mm were significantly lower than those in patients with an ascending aortic diameter < 46 mm (66.7% vs. 100% at 5 years, p < 0.0001). CONCLUSION: Aortic regurgitation combined with ascending aortic dilatation at aortic valve replacement could be a significant risk factor for late aortic dissection.

Configuration of the neoaortic root after chimney reconstruction in the Norwood procedure.

OBJECTIVES: After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. METHODS: Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5-6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. RESULTS: The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. CONCLUSIONS: Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.

Giant coronary pseudoaneurysm associated with stent fracture treated successfully with coil embolization and a vascular plug.

A 59-year-old man with acute cholangitis was referred to us because of a coronary artery aneurysm that was incidentally detected on contrast-enhanced computed tomography. Intravascular ultrasonography showed a loss of vascular layers and complete stent fracture, which was suggestive of a pseudoaneurysm. After some management protocols, such as observation, covered stent implantation, and surgical treatment, had failed, we treated the pseudoaneurysm successfully using coil embolization and a vascular plug. There were no complications during the perioperative period. We suggest that, if conventional management fails, treatment with coil embolization and a vascular plug should be considered. Learning objective: A rare complication of percutaneous coronary intervention resulting from stent fracture is a coronary artery aneurysm. Here, we discuss the chronic complications of stent implantation and discuss the optimal management strategy for coronary pseudoaneurysms. Further, we discuss the strengths and weaknesses of each strategy.

Multiple Pulmonary Artery Plasty With Tissue-Engineered Vascular Grafts.

In pediatric cardiovascular surgery, the autologous pericardium is useful for pulmonary artery augmentation. However, in some cases, the autologous pericardium may not be available for various reasons. Since 2014, we have developed tissue-engineered vascular grafts (TEVGs) and obtained good results. We report a successful case of multiple pulmonary artery plasty with TEVGs for pulmonary atresia/ventricular septal defect with major aortopulmonary collateral arteries. TEVGs are useful alternatives to autologous pericardium in pediatric cardiovascular operations that often require multistage procedures.

A new predictor of the optimal pulmonary artery reconstruction method during the arterial switch operation.

OBJECTIVES: The aim of this study was to more accurately predict the optimal pulmonary artery (PA) reconstruction procedure (Lecompte manoeuvre or original Jatene procedure) during the arterial switch operation, we focused on the horizontal sectioning (HS) angle between the left hilum PA and the great arteries using preoperative computed tomography imaging. METHODS: We defined the HS angle α (ß) as the angle between the tangential line from the posterior (anterior) wall of the left PA at the hilum to the left anterior (right posterior) surface of the main PA and the tangential line from the left surface of the ascending aorta to the left anterior (right posterior) surface of the main PA. We identified 14 consecutive patients diagnosed with transposition of the great arteries or transposition of the great artery-type double-outlet right ventricle who underwent preoperative computed tomography imaging. The original Jatene or Lecompte procedure was used for 9 (OJ group) and 5 (L group) patients. Relationships of the great arteries of the OJ and L groups were side by side in 8 and 2 patients, oblique in 1 and 1 patient and anteroposterior in 0 and 2 patients, respectively. RESULTS: In the OJ group, ß was greater than α in all patients. The median α/ß value was 0.618. In group L, α was greater than ß in all patients. The median α/ß was 1.307. Left PA stenosis caused by stretching was not observed in the L group. Coronary obstruction was not identified in the OJ group. Left PA stenosis behind the neo-ascending aorta was observed in 1 patient in the OJ group and required reoperation. CONCLUSIONS: The HS angle may be a useful predictor of optimal intraoperative PA reconstruction during arterial switch operation, especially for side-by-side or oblique relationships.

Impact of Intensive Low-Density Lipoprotein Cholesterol-Lowering Therapy on Coronary Artery Plaques in Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is associated with a high incidence of unstable plaques beyond the culprit lesion, leading to early recurrence of cardiovascular events. Coronary computed tomography angiography (CCTA) can be used to noninvasively observe plaques throughout the coronary arteries. To evaluate the impact of intensive low-density lipoprotein cholesterol (LDL-C)-lowering therapy on quantitative changes in coronary plaque, assessed using CCTA in a study population with ACS. In total, 81 consecutive patients with ACS who underwent CCTA at discharge and at 1-year follow-up from April 2018 to March 2020 were analyzed. The patients were divided into 2 groups: those who achieved LDL-C <70 mg/100 ml and those who did not. Changes in plaque morphology within and between the 2 groups were compared using CCTA. A total of 198 vessels were analyzed. The calcified plaque volume was significantly increased in the LDL-C <70 group (65.8 ± 80.1 mm3 to 73.6 ± 83.7 mm3, p = 0.007), whereas no significant change was observed in the LDL-C ≥70 group (106.9 ± 161.7 mm3 to 105.7 ± 137.5 mm3, p = 0.552). Percent change in low-attenuation plaque volume in the LDL <70 group was significantly lower than in the LDL-C ≥70 group (17.2 ± 90.9% vs 84.4 ± 162.6%, p = 0.020). Receiver operating characteristic curve analysis demonstrated that the target LDL-C level for low-attenuation plaque volume regression was 64 mg/100 ml. In conclusion, noninvasive CCTA demonstrated that intensive LDL-C lowering in high-risk patients with ACS could potentially lead to plaque stabilization.

Angiographic Coronary Calcification: A Simple Predictor of Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.

AIMS: Coronary calcification detected by coronary angiography is a simple risk marker for long-term clinical outcomes in stable coronary artery disease. However, the significance of angiographic coronary calcification in the culprit lesion of acute myocardial infarction (AMI) has not been fully discussed. The purpose of this retrospective study was to assess the usefulness of angiographic coronary calcification as a risk marker for long-term clinical outcomes following percutaneous coronary intervention to the culprit lesions of AMI. METHODS: We included 1209 patients with AMI and divided them into the none-mild calcification group (n=923) and the moderate-severe calcification group (n=286) according to angiographic coronary calcification in the culprit lesion of AMI. The primary endpoint was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, nonfatal MI, readmission for heart failure, and ischemia-driven target vessel revascularization. RESULTS: The median follow-up duration was 542 (Q1: 182, Q3: 990) days. A total of 345 MACE were observed during the study period. The occurrence of MACE was significantly greater in the moderate-severe calcification group than in the none-mild calcification group (43.4% vs. 23.9%, p＜0.001). In the multivariate Cox hazard model, moderate-severe calcification was significantly associated with MACE (hazard ratio 1.302, 95% confidence interval 1.011-1.677, p=0.041) after controlling multiple confounding factors. CONCLUSIONS: Angiographically moderate to severe calcification in AMI culprit lesion was associated with long-term worse clinical outcomes. Angiographic coronary calcification can be a simple risk marker in patients after AMI.

Coronary artery bypass grafting for coronary artery anomalies in infants and young children.

OBJECTIVES: Coronary artery bypass grafting (CABG) has been reported for coronary artery diseases in patients with Kawasaki disease and coronary artery complications after arterial switch operations for transposition of the great arteries. However, only a few studies have explored this modality for congenital coronary artery anomalies. As congenital coronary artery anomalies, particularly left coronary artery atresia and stenosis, are one of the reasons for sudden death, coronary revascularization is often required in infants and young children. Therefore, we aimed to investigate the outcome of CABG for such anomalies in infants and young children. METHODS: From 2014 to 2018, 3 infants and 2 children (median age: 10 months; range: 6-40 months) with coronary artery anomalies underwent CABG at our hospital. The indications for the procedure included left main coronary artery atresia and stenosis in 2 and 3 patients, respectively. Graft patency was evaluated postoperatively by contrast-enhanced computed tomography or coronary angiography, and postoperative outcomes (including death and cardiac events) were assessed during the follow-up period. RESULTS: No 30-day or in-hospital mortalities were noted. Postoperative examinations revealed patent grafts in all patients. They were discharged without any cardiac complications. Regarding the outcomes at the follow-up period, the graft patency rate was 80.0% (4/5 grafts), with no deaths or cardiac events. CONCLUSIONS: CABG is a useful strategy for coronary revascularization in infants and young children with coronary artery anomalies. Although the mid-term outcomes and patency are satisfactory, careful follow-up is necessary because the long-term outcomes remain unknown.

Surgical repair of a posterior left ventricular aneurysm in a 4-year-old boy.

Left ventricular aneurysms are rarely encountered in pediatric patients. A 4-year-old boy was diagnosed with severe mitral regurgitation and a posterior left ventricular aneurysm associated with a viral infection. The aneurysm was surgically resected and plicated longitudinally with a combination of an interrupted mattress and continuous over-and-over sutures with an outer felt reinforcement. The mitral regurgitation was reduced to a trivial degree postoperatively. The patient's postoperative recovery was good. He was discharged 31 days after surgery without cardiac dysfunction or lethal arrhythmia. Considering the location and spread of the aneurysm, an appropriate surgical procedure should be adopted for pediatric patients.

Factors associated with difficulty in crossing the culprit lesion of acute myocardial infarction.

In percutaneous coronary intervention (PCI) to the culprit lesion of acute myocardial infarction (AMI), unsuccessful guidewire crossing causes immediate poor outcomes. It is important to determine the factors associated with unsuccessful guidewire crossing in AMI lesions. The purpose of this study was to find factors associated with difficulty in crossing the culprit lesion of AMI. We defined the difficult group when the guidewire used to cross the culprit lesion was a polymer jacket type guidewire or a stiff guidewire. We included 937 patients, and divided those into the non-difficult group (n = 876) and the difficult group (n = 61). Proximal reference diameter was significantly smaller in the difficult group than in the non-difficult group (p < 0.001), and degree of calcification was severer in the difficult group than in the non-difficult group (p < 0.001). In the multivariate stepwise logistic regression analysis, proximal reference diameter [odds ratio (OR) 0.313, 95% confidence interval (CI) 0.185-0.529, p < 0.001)], previous PCI (OR 3.065, 95% CI 1.612-5.830, p = 0.001), moderate-severe calcification (OR 4.322, 95% CI 2.354-7.935, p < 0.001), blunt type obstruction (OR 12.646, 95% CI 6.805-23.503, p < 0.001), and the presence of collateral to the culprit lesion (OR 2.110, 95% CI 1.145-3.888, p = 0.017) were significantly associated with difficulty in crossing the culprit lesion. In conclusion, previous PCI, calcification, blunt type obstruction, and the presence of collateral were associated with difficulty in crossing the culprit lesion, whereas proximal reference diameter was inversely associated with difficulty. Our study provides a reference to recognize the difficulty in crossing the culprit lesions of AMI for PCI operators, especially junior operators.

Chimney reconstruction provides a wider subaortic space and reduces the risk of pulmonary artery compression in the Norwood-type aortic arch reconstruction without patch supplementation.

OBJECTIVES: Pulmonary artery (PA) compression by the neoaorta is a serious complication after the Norwood-type palliation (NP) for hypoplastic left heart syndrome. Either excess patch tailoring or limited use of autologous tissue may cause narrowing of the subaortic space. The chimney technique could theoretically provide a wide subaortic space. METHODS: Twenty-nine patients with both pre- and post-NP computed tomography data available of the 37 consecutive patients who underwent NP in our institution were reviewed. Arch height, arch width, sinus of Valsalva diameter, area under the neoaortic arch and arch angle were measured. These patients were divided according to the neo-arch reconstruction technique, chimney reconstruction technique (CR) or conventional direct reconstruction technique (DR). RESULTS: Median age and weight at NP were 2.1 months and 3.5 kg, respectively. Twenty-two patients underwent previous bilateral PA banding. During NP, 17 CR and 12 DR were performed. Four patients in the DR group developed PA compression. No neoaortic arch dilatation was found in either group. Post-NP arch width, area under the neo-arch and the arch angle were significantly larger in the CR group. Pre-NP arch height was significantly smaller in DR patients with PA compression than in those without. CONCLUSIONS: The chimney technique decreased the risk of PA compression and provided a wider subaortic space and a less acute arch angle. This technique had no short-term effect on the neoaortic root. Small preoperative arch height is a potential risk factor for PA compression in DR, and the chimney technique could be an effective solution.

Comparison of half-turned truncal switch and conventional operations.

OBJECTIVES: To compare conventional procedures with the half-turned truncal switch operation (HTTSO) for the management of complete transposition of the great arteries with left ventricular outflow tract (LVOT) obstruction using time-resolved 3-dimensional magnetic resonance phase-contrast imaging. METHODS: We identified 2 cases that underwent the Rastelli procedure and one case that underwent the Réparation a l'étage ventriculaire before 2002 [conventional procedures group (group C)], and 16 cases of HTTSO that were performed between 2002 and 2020 [HTTSO group (group H)]. Postoperative haemodynamics were assessed using time-resolved 3-dimensional magnetic resonance phase-contrast imaging in cases in both groups. RESULTS: The median follow-up period was 20.4 years in group C, and 6.1 years in group H. In group C, all 3 patients underwent reoperation because of postoperative right ventricular outflow tract obstruction and/or insufficiency. In addition, permanent pacemaker implantation was needed in 1 patient because of complete atrioventricular block complicated by ventricular septal defect enlargement. In group H, reoperation for LVOT/right ventricular outflow tract obstruction was not needed. A time-resolved 3-dimensional magnetic resonance phase-contrast imaging examination revealed high energy loss and wall shear stress in the winding LVOT in the group C. In contrast, low energy loss and wall shear stress, with straight and smooth LVOT, were identified in group H. CONCLUSIONS: HTTSO was shown to be superior to conventional procedures because a straight and wide LVOT could be obtained. Therefore, HTTSO should be the first choice for complete transposition of the great arteries with LVOT obstruction.

Histopathologic Analysis of Explanted Polytetrafluoroethylene-Valved Pulmonary Conduits.

The expanded polytetrafluoroethylene (ePTFE)-valved conduits as alternative material for right ventricular outflow reconstruction provides satisfactory long-term outcomes. The purpose of this study was to investigate degenerative changes in failed conduits through histopathologic analysis of the explanted specimens. All leaflets of explanted conduits were observed macroscopically, and their longitudinal sections were examined microscopically. Three typical findings, that is, calcification of the leaflet, neointimal proliferation, and proteinaceous infiltration into the leaflet, were evaluated quantitatively by measuring their degree and appearance probability. A total of 15 leaflets from 5 failed conduits (group F) and 12 leaflets from 5 nonfailed conduits (group non-F) were included. The median duration of implantation was 7.6 years (5.3-10.9 years) in group F and 1.3 years (0.7-3.9 years) in group non-F (P = 0.003). In group F, calcification tended to occur in the middle and upper third of the leaflet, causing stiffening, distortion, and exophytic concretion of the leaflet, and mean neointimal thickness on inflow and outflow surfaces were 0.33 ± 0.02 mm and 0.22 ± 0.01 mm, respectively. There was a moderately strong correlation between appearance probability of calcification in group F and that of proteinaceous infiltration in group non-F (correlation coefficient 0.67, P < 0.001). Proteinaceous infiltration into the leaflet was presumed be responsible for future calcification of the leaflet and subsequent stenotic conduit failure. Modification of the ePTFE material to prevent proteinaceous infiltration may contribute to improving the durability of ePTFE-valved conduit.