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Background: Atrial functional mitral regurgitation (AFMR), defined by normal left ventricular function, enlarged left atrium, and a dilated mitral valve annulus, has been a concept discussed for >10 years. However, there are still no established guidelines for its treatment in the American College of Cardiology/American Heart Association recommendations. This study aimed to determine the long-term outcomes of mitral annuloplasty as a treatment for AFMR., Methods: We analyzed 1435 patients who underwent mitral valve repair at our institution between 2005 and 2020, with 162 classified as having AFMR. Exclusion criteria for AFMR were established based on preoperative echocardiography and operative notes. The primary outcome was overall mortality, and the secondary outcome was MR recurrence, which was defined as moderate or greater mitral regurgitation observed on echocardiography during the follow-up period, analyzed using our hospital's medical records and data from the National Statistical Office., Results: The median follow-up duration for the entire patient cohort was 6.1 years (interquartile range, 3.2-11.2 years). Patients had a 5-year survival rate of 86% and a 10-year survival rate of 73%, with freedom from MR recurrence rates of 89% and 80% at 5 and 10 years, respectively. Although all 162 patients had moderate or greater MR before surgery, most experienced trivial or mild MR after mitral valve repair throughout the follow-up period., Conclusions: In summary, mitral valve repair effectively treats patients with AFMR, addressing survival and mitigating MR recurrence., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model., Methods: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment., Results: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups., Conclusion: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease., (Copyright © 2023. Published by Elsevier B.V.)

Background: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown., Methods: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery., Results: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis., Conclusions: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG., (© 2024. The Author(s).)

Captopril (CTP) is an oral drug widely used to treat high blood pressure and congestive heart failure. In this study, CTP-incorporated biomaterials for antihypertensive therapy were synthesized from chitosan, carboxymethyl cellulose, and plasticizers. The physicochemical properties of the prepared biomaterials were characterized using FE-SEM, FT-IR analysis, and physical properties. CTP release experiments were carried out in buffer solutions at various pH values and temperatures. Results indicated that above 99.0 % of CTP was released within 180 min. Optimization of the experimental conditions for CTP release was analyzed by using response surface methodology (RSM). Results of CTP release through artificial skin indicated that CTP was continuously released above 95.0 % from the prepared biomaterials for 36.0 h. The CTP release mechanisms into a buffer and through artificial skin followed pseudo-Fickian diffusion mechanism and non-Fickian diffusion mechanisms, respectively. Moreover, angiotensin-converting enzyme (ACE) inhibition (related to cardiovascular disease) via the released CTP clearly reveals that the prepared biomaterials have a high potential as a transdermal drug delivery agent in antihypertensive therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Intimal hyperplasia (IH) is a major cause of vascular restenosis after bypass surgery, which progresses as a series of processes from the acute to chronic stage in response to endothelial damage during bypass grafting. A strategic localized drug delivery system that reflects the pathophysiology of IH and minimizes systemic side effects is necessary. In this study, the sequential release of sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, and statin, an HMG-COA inhibitor, was realized as a silk fibroin-based microneedle device in vivo. The released sirolimus in the acute stage reduced neointima (NI) and vascular fibrosis through mTOR inhibition. Furthermore, rosuvastatin, which was continuously released from the acute to chronic stage, reduced vascular stiffness and apoptosis through the inactivation of Yes-associated protein (YAP). The sequential release of sirolimus and rosuvastatin confirmed the synergistic treatment effects on vascular inflammation, VSMC proliferation, and ECM degradation remodeling through the inhibition of transforming growth factor (TGF)-beta/NF-κB pathway. These results demonstrate the therapeutic effect on preventing restenosis with sufficient vascular elasticity and significantly reduced IH in response to endothelial damage. Therefore, this study suggests a promising strategy for treating coronary artery disease through localized drug delivery of customized drug combinations., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Off-pump coronary surgery requires mechanical cardiac displacement, which results in bi-ventricular systolic and diastolic dysfunction. Although transient, subsequent hemodynamic deterioration can be associated with poor prognosis and, in extreme cases, emergency conversion to on-pump surgery, which is associated with high morbidity and mortality. Thus, appropriate decision-making regarding whether the surgery can be proceeded based on objective hemodynamic targets is essential before coronary arteriotomy. For adequate hemodynamic management, avoiding myocardial oxygen supply-demand imbalance, which includes maintaining mean arterial pressure above 70 mmHg and preventing an increase in oxygen demand beyond the patient's coronary reserve, must be prioritized. Maintaining mixed venous oxygen saturation above 60%, which reflects the lower limit of adequate global oxygen supply-demand balance, is also essential. Above all, severe mechanical cardiac displacement incurring compressive syndromes, which cannot be overcome by adjusting major determinants of cardiac output, should be avoided. An uncompromising form of cardiac constraint can be ruled out as long as the central venous pressure is not equal to or greater than the pulmonary artery diastolic (or occlusion) pressure, as this would reflect tamponade physiology. In addition, transesophageal echocardiography should be conducted to rule out mechanical cardiac displacement-induced ventricular interdependence, dyskinesia, severe mitral regurgitation, and left ventricular outflow tract obstruction with or without systolic motion of the anterior leaflet of the mitral valve, which cannot be tolerated during grafting. Finally, the ascending aorta should be carefully inspected for gas bubbles to prevent hemodynamic collapse caused by a massive gas embolism obstructing the right coronary ostium.

Purpose: It is unclear if a second or third arterial graft can improve clinical outcomes in coronary artery bypass graft surgery. We compared the outcomes of bilateral internal thoracic artery (BITA) plus radial artery (RA) grafting versus left internal thoracic artery (LITA) plus RA grafting after off-pump coronary artery bypass grafting., Materials and Methods: Between January 2009 and December 2020, a total of 3007 patients with three-vessel coronary artery disease who underwent off-pump coronary artery bypass were analyzed. Among them, 971 patients received total arterial grafting using LITA. We divided the patients into two groups [group A, BITA+RA grafting (n=227) and group B, LITA+RA grafting (n=744)], and compared the survival and major adverse cardiac and cerebrovascular event (MACCE) rates between the two groups at 10 years., Results: After risk adjustment with inverse probability treatment weighting methods, the freedom from all-cause mortality was 93.1% and 88.3% in groups A and B, respectively ( p =0.140). The freedom from MACCE rates were 68.3% and 89.0%, respectively ( p <0.0001). LITA plus RA grafting [hazard ratio (HR): 1.3, 95% confidence interval (CI): 1.05-2.37, p =0.025] and incomplete revascularization (HR 1.2, 95% CI: 0.70-2.15, p =0.046) were significant risk factors for MACCEs in multivariable Cox regression analysis., Conclusion: The rates of MACCEs were lower with LITA plus RA grafting than with BITA plus RA grafting in total arterial revascularization. Furthermore, complete revascularization improved long-term outcomes following total arterial grafting., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Background: Flowable hemostatic agents have the advantage of being able to be applied to irregular wound surfaces and difficult to reach areas. We sought to compare the effectiveness and safety of the flowable hemostatic sealants Collastat® (collagen hemostatic matrix, [CHM]) and Floseal® (gelatin hemostatic matrix, [GHM]) during off-pump coronary artery bypass (OPCAB)., Methods: In this prospective, double-blind, randomized controlled trial, 160 patients undergoing elective OPCAB surgery were enrolled between March 2018 and February 2020. After primary suture of the aortocoronary anastomosis, an area of hemorrhage was identified, and patients received either CHM or GHM (n = 80, each). Study endpoints were the following: proportion of successful intraoperative hemostasis and time required for hemostasis overall postoperative bleeding, proportion of transfusion of blood products, and surgical revision for bleeding., Results: Of the total patients, 23% were female, and the mean age was 63 years (range 42-81 years). Successful hemostasis proportion within 5 min was achieved for 78 patients (97.5%) in the GHM group, compared to 80 patients (100%) in the CHM group (non-inferiority p = 0.006). Two patients receiving GHM required surgical revision to achieve hemostasis. There were no differences in the mean time required to obtain hemostasis [GHM vs. CHM, mean 1.49 (SD 0.94) vs. 1.35 (0.60) min, p = 0.272], as confirmed by time-to-event analysis (p = 0.605). The two groups had similar amounts of mediastinal drainage for 24 h postoperatively [538.5 (229.1) vs. 494.7 (190.0) ml, p = 0.298]. The CHM group required less packed red blood cells, fresh frozen plasma, and platelets for transfusion than the GHM group (0.5 vs. 0.7 units per patient, p = 0.047; 17.5% vs. 25.0%, p = 0.034; 7.5% vs. 15.0%, p = 0.032; respectively)., Conclusions: CHM was associated with a lower need for FFP and platelet transfusions. Thus, CHM is a safe and effective alternative to GHM., Trial Registration: ClinicalTrials.gov, NCT04310150., (© 2023. The Author(s).)

Transit-time flowmetry (TTFM) is commonly used during coronary artery bypass grafting for intraoperative graft assessment. This study aimed to investigate whether TTFM values were predictive of graft failure and major adverse cardiac and cerebrovascular events (MACCEs). Between 2011 and 2018, 1933 patients with 3-vessel coronary artery disease who underwent off-pump coronary artery bypass were retrospectively analyzed. Among them, 1288 sequential venous grafts in 538 consecutive patients were measured using TTFM's 2 parameters, pulsatility index (PI) and flow (mL/min). The anastomoses were divided in the 3 groups depending on the anastomotic site: group A, first side-to-side anastomoses (n = 538), group B; second side-to-side (n = 212), group C; end-to-side (n = 538). MACCEs were related to TTFM. The mean clinical follow-up time was 64.8 ± 21.2 months. Postoperative graft patency was confirmed with multi-slice computed tomography or coronary angiography (follow-up interval: 64.8 ± 50.4 and 27.8 ± 20.5 months based on the date of examination). The 5-year survival rate was 93.7%. The mean graft flow was 59.1 ± 31.3, 41.0 ± 25.2, and 38.9 ± 22.8 mL/minute, and the PI was 2.2 ± 1.3, 2.5 ± 3.4, and 2.4 ± 2.5, in groups A, B, and C, respectively. Graft failure occurred in 23/1055 (2.2%) anastomoses. The 5-year MACCE rate was 6.9% (37/538 patients). Kaplan-Meier analysis revealed that graft patency was significantly lower in low MGF (p = 0.044) and high PI (p < 0.001). Multivariable logistic analysis showed that high PI (>5; HR 2.276; 95%CI 2.188-2.406, p < 0.001) was an independent risk factor for MACCEs. The cutoff values for PI of sequential grafts were 3.65, 3.55, and 3.17 in groups A, B, and C, respectively for the prediction of MACCE. A high PI predicts more predictive poor outcomes of sequential venous grafts after surgery than the low mean graft blood flow., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Wearable blood-pressure sensors have recently attracted attention as healthcare devices for continuous non-invasive arterial pressure (CNAP) monitoring. However, the accuracy of wearable blood-pressure (BP) monitoring devices has been controversial due to the low signal quality of sensors, the absence of an accurate transfer function to convert the sensor signals into BP values, and the lack of clinical validation regarding measurement precision. Here, a wearable piezoelectric blood-pressure sensor (WPBPS) is reported, which achieves a high normalized sensitivity (0.062 kPa -1 ), and fast response time (23 ms) for CNAP monitoring. The transfer function of a linear regression model is designed, offering a simple solution to convert the flexible piezoelectric sensor signals into BP values. In order to verify the measurement accuracy of WPBPS, clinical trials are performed on 35 subjects aged from 20 to 80 s after screening. The mean difference between the WPBPS and a commercial sphygmomanometer of 175 BP data pairs is -0.89 ± 6.19 and -0.32 ± 5.28 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. By building a WPBPS-embedded wristwatch, the potentially promising use of a convenient, portable, continuous BP monitoring system for cardiovascular disease diagnosis is demonstrated., (© 2023 Wiley-VCH GmbH.)

Background: This study aimed to compare the outcomes of aspirin in combination with either ticagrelor or clopidogrel after off-pump coronary artery bypass (OPCAB) in patients with clopidogrel resistance., Methods: Between November 2014 and November 2020, 1739 patients underwent OPCAB. Aspirin and clopidogrel treatment was initiated the day after surgery. On postoperative days 7 to 9, clopidogrel resistance was evaluated using a point-of-care assay. A total of 278 (18.9%) patients had clopidogrel resistance ( platelet reaction unit >208) and were enrolled in the study. The study investigators excluded patients with coresistance to aspirin (n = 74) and divided the remaining patients (mean age, 67.4 ± 8.5 years) into 2 groups (an aspirin and ticagrelor group [AT group; n = 102] and an aspirin and clopidogrel group [AC group; n = 102]), randomly assigned using a 1:1 ratio block table. The primary end point was graft patency and major adverse cardiovascular events (MACEs; defined as the composite of cardiovascular mortality, myocardial infarction, and repeat revascularization at 1 year after OPCAB), and the coprimary end point was the graft patency rate. The data were analyzed using the intent-to-treat method., Results: The graft occlusion rates in the AT and AC groups were 3.9% and 5.9%, respectively (P = .52). Neither death from cardiovascular causes (1.0% vs 2.9%; P = .32) nor myocardial infarction showed significant differences (1.0% vs 3.9%; P = .18). No significant difference in the rates of major bleeding were found between the 2 groups (P = .75). However, the AT group was associated with a lower rate of MACEs after OPCAB (hazard ratio, 0.77; 95% CI, 0.684-0.891; P = .01)., Conclusions: These results suggest that ticagrelor may be associated with reducing MACEs in patients with clopidogrel resistance after OPCAB., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated the effect of residual arch tears on late reinterventions and arch dilatation after hemiarch replacement for patients with acute DeBakey type I aortic dissection., Methods: Between January 1995 and October 2018, 160 consecutive patients who underwent hemiarch replacement for DeBakey type I dissection were retrospectively enrolled. They were divided into patients with (n = 73) and without (n = 87) residual arch tears. The arch tears group was subdivided into the proximal/middle arch (n = 26) and distal arch (n = 47) groups to evaluate arch growth rates according to the locations of residual arch tears. The endpoints were arch growth rate and late arch and composite events., Results: The arch diameter increased significantly over time in patients with residual arch tears (1.620 mm/y, P < .001). The increase occurred more rapidly when residual tears occurred at the distal arch than at the proximal/middle arch level (2.101 vs 1.001 mm/y). In the adjusted linear mixed model, residual arch tears or luminal communications at the distal arch level were significant factors associated with increases in the arch diameter over time. The 10-year freedom from late arch and composite event rate was significantly lower for patients with residual arch tears than for those without (82.4% vs 95.5%, P = .001; and 68.0% vs 89.3%, P = .002, respectively)., Conclusions: Residual arch tears are significant factors associated with late arch dilatation and reinterventions, especially for patients with distal arch tears. Extensive arch replacement during the initial surgery to avoid residual arch tears may improve long-term outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients scheduled for cardiac surgery often have anemia and iron deficiency. We investigated the effect of the preoperative administration of intravenous ferric carboxymaltose (IVFC) in patients with iron deficiency anemia (IDA) who were due to undergo off-pump coronary artery bypass grafting (OPCAB). Patients who were due to undergo elective OPCAB between February 2019 and March 2022 who had IDA ( n = 86) were included in this single center, randomized, parallel-group controlled study. The participants were randomly assigned (1:1) to receive either IVFC or placebo treatment. Postoperative hematologic parameters [hemoglobin (Hb), hematocrit, serum iron concentration, total iron-binding capacity, transferrin saturation, transferrin concentration, and ferritin concentration] and the changes in these parameters during the follow-up period were the primary and secondary outcomes, respectively. The tertiary endpoints were early clinical outcomes, such as the volume of mediastinal drainage and the need for blood transfusions. IVFC treatment significantly reduced the need for red blood cell (RBC) and platelet transfusions. Despite receiving fewer RBC transfusions, patients in the treatment group had higher levels of Hb, hematocrit, and serum iron and ferritin concentrations during weeks 1 and 12 after surgery. No serious adverse events occurred during the study period. Preoperative IVFC treatment in patients with IDA undergoing OPCAB improved the values of the hematologic parameters and iron bioavailability. Therefore, is a useful strategy for stabilizing patients prior to OPCAB.

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Purpose: Pulmonary thromboembolism is a potentially life-threatening condition in patients with heart disease; however, limited studies discussing long-term outcomes exist. This study aimed to investigate the long-term outcomes of pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), focusing on the improvement of functional class and right ventricular (RV) pressure., Materials and Methods: Clinical data of patients with CTEPH were obtained from Yonsei Hospital between May 2012 and December 2021, and reviewed retrospectively. Twenty-six patients underwent endoscope-guided PEA during the study period, and the mean follow-up duration was 24.8±23.4 months., Results: After PEA, most patients (88.5%) were weaned from inotropes without extracorporeal membrane oxygenation support during the first few days. Two patients (7.6%) had cerebrovascular accidents without neurological deficits. On echocardiography, the RV systolic pressure and tricuspid regurgitation grades significantly improved ( p <0.001). Furthermore, the mean left ventricle end-diastolic diameter was significant increased ( p =0.003), and the left ventricular end-systolic diameter increased ( p <0.001). The median intensive care unit stay was 3.0±9.4 days, and median hospital stay 16.0±26.5 days. The 5-year survival rate was 95.5%, and the 5-year freedom rate of cardiac death was 100%. There was a marked improvement in New York Heart Association (NYHA) status ( p <0.001). Cox regression suggested that the main pulmonary artery (MPA) involvement is a significant predictor of non-improvement in functional class post-PEA., Conclusion: Mortality rates are low and patients experience a marked improvement in NYHA class and health status after PEA. Moreover, MPA involvement may affect functional outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Background: The aim of this study was to investigate whether distal aortic maximum false lumen area (MFLA) ratio predicts late aortic dilation and reintervention after open repair of acute type I aortic dissection., Methods: We analyzed 309 nonsyndromic acute type I aortic dissection patients who were treated with a repair to the proximal aorta between 1994 and 2017. In 230 patients who did not show completely thrombosed false lumen on postoperative computed tomography, the MFLA ratio (MFLA/aortic area) on the descending thoracic aorta (DTA) was measured with postoperative computed tomography. Patients were divided into 3 groups according to the quartile range of MFLA ratio: low MFLA, <0.62 (n = 57); intermediate MFLA, 0.62 to 0.81 (n = 116); and high MFLA, ≥0.82 (n = 57)., Results: The aortic expansion rate was significantly higher in the high MFLA group (11.1 ± 21.2 mm/y) compared with intermediate (3.0 ± 7.4 mm/y; P < .01) and low (0.6 ± 6.6 mm/y; P < .01) MFLA groups. High MFLA was found to be an independent risk factor for significant aortic expansion (adjusted hazard ratio, 5.26; 95% CI, 1.53-18.12; P < .01) and aorta-related reintervention (hazard ratio, 4.99; 95% CI, 2.23-11.13; P < .01), and the MFLA ratio was significantly related to proximal DTA reentry tears (adjusted odds ratio, 12974.3; P < .001; area under curve, 0.807)., Conclusions: A high MFLA ratio on the DTA after acute type I aortic dissection repair is associated with increased risk of late aortic reintervention and distal aortic dilation. A high MFLA ratio is strongly associated with proximal DTA reentry tears., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Infective endocarditis is a life-threatening condition and is associated with embolic events. We aimed to evaluate the association of vegetation size, multiplicity, and position with cerebral embolism and late mortality in patients with infective endocarditis., Methods: We retrospectively reviewed patients with infective endocarditis who were admitted to a single institution between November 2005 and August 2017. A total of 419 patients with infective endocarditis were included in the study, 273 of whom had undergone surgery. The primary endpoint was all-cause mortality, and the secondary endpoint was cerebral embolism. Multivariate Cox regression and logistic regression analyses were performed to identify independent risk factors for 30-day mortality, late mortality, and cerebral embolism., Results: Age (hazard ratio [HR] 1.02; 95% confidence interval [CI], 1.00 to 1.04), renal failure (HR 4.21; 95% CI, 2.67 to 6.65), surgery (HR 0.31; 95% CI, 0.21 to 0.46), and Acute Physiology and Chronic Health Evaluation II score (HR 1.08; 95% CI, 1.01 to 1.15) were associated with late mortality. Vegetation size, multiplicity, and position were not significantly associated with late mortality, but a mitral vegetation size of greater than 10 mm (odds ratio 2.25; 95% CI, 1.32 to 3.84) was an independent risk factor for cerebral embolism., Conclusions: A vegetation size of greater than 10 mm and the mitral position were found to be significant risk factors for cerebral embolism, and for this group, early surgery might be considered to prevent cerebral embolism., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (Afib) is a marker of increased cardiovascular morbidity and mortality. Owing to the increased prevalence of Afib in patients undergoing cardiac surgery, assessing the effect of Afib on postsurgical outcomes is important. We aimed to analyze the effect of preoperative Afib on clinical outcomes in patients undergoing cardiac surgery using a large surgical database., Methods: This retrospective cohort study was based on the national health claims database established by the National Health Insurance Service of the Republic of Korea from 2009 to 2015. Diagnosis and procedure codes were used to identify diseases according to the International Statistical Classification of Diseases, 10th revision., Results: We included 1,037 patients (0.1%) who had undergone cardiac surgery from a randomized 1,000,000-patient cohort, and 15 patients (1.5%) treated with isolated surgical Afib ablation were excluded. Of these 1,022 patients, 412 (39.7%), 303 (29.2%), and 92 (9.0%) underwent coronary artery bypass, heart valve surgery, and Cox-maze surgery, respectively. Preoperative Afib was associated with higher patient mortality (p=0.028), regardless of the surgical procedure. Patients with preoperative Afib (n=190, 18.6%) experienced a higher cumulative risk of overall mortality (hazard ratio [HR], 1.435; 95% confidence interval [CI], 1.263-2.107; p=0.034). Subgroup analysis revealed a reduced risk of overall mortality with Cox-maze surgery in Afib patients (HR, 0.500; 95% CI, 0.266-0.938; p=0.031). Postoperative cerebral ischemia or hemorrhage events were not related to Afib., Conclusion: Preoperative Afib was independently associated with worse long-term postoperative outcomes after cardiac surgery. Concomitant Cox-maze surgery may improve the survival rate.

Although autologous vein grafting is essential, the high vein failure rate and specific clinical interventions are not clear, so a potential treatment is critically needed; thus, complex analyses of the relationship between pathobiological and physiological processes in preclinical are essential. The interposition of the femoral vein was performed in a canine model. Maximized expansion and velocity were measured at 8 weeks post-implantation, and a relative decrease was observed at 12 weeks. However, NI formation and NI/Media ratio significantly increased time dependently, and differences between the mechanical properties were observed. Additionally, RhoA-mediated TNF-α induced by rapid structural changes and high shear stress was confirmed. After adaptation to the arterial environment, vascular remodeling occurred by SMC proliferation and differentiation, apoptosis and autophagy were induced through YAP activity without vasodilation and RhoA activity. Our results show that understanding pathobiological processes in which time-dependent physiological changes contribute to vein failure can lead to a potential strategy. The implanted vein graft within the arterial environment undergoes pathobiological processes through RhoA and YAP activity, leading to pathophysiological changes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The study objective was to examine the long-term fate of aortic diameter expansion at 4 cardiac regions (annulus, sinus, ascending aorta, and proximal arch) after wrapping or replacement during aortic valve surgery of the moderately dilated ascending aorta., Methods: From January 1995 to December 2018, 964 consecutive patients who underwent aortic valve replacement at our institution were reviewed. Of them, 204 (mean age, 60.7 ± 7.4 years) underwent ascending aorta wrapping (n = 96) or replacement (n = 108) for a moderately dilated ascending aorta (40 to 55 mm). The overall fate of the aortic diameter was analyzed with a linear mixed-effect model. The median follow-up duration was 7.1 years., Results: After propensity score matching, the baseline maximal ascending aortic diameter median value was 47.3 ± 3.1 mm and 49.4 ± 13.5 mm in the wrapping and replacement groups, respectively. The annulus, sinus, and ascending aorta did not redilate in either group. The proximal aortic arch diameter significantly increased over time (0.343 mm/year; P = .006) in the wrapping group but not in the replacement group (0.066 mm/year; P = .649). Multivariable competing risk analysis identified the initial ascending aorta diameter at the wrapping procedure as an independent risk factor of proximal arch redilation (0.071 ± 0.037, P < .001). The cutoff value was an initial ascending aorta diameter of 47.2 mm for the prediction proximal arch redilation (area under the curve, 0.703; P = .014)., Conclusions: Aortic wrapping and replacement may be long-term durable treatment options in patients with a moderately enlarged ascending aorta. We suggest careful evaluation of redilation in the proximal arch after an aorta wrapping procedure., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles that contribute to the pathogenesis of atrial fibrillation (AF). Here, we investigated the role of sEVs derived from patients with persistent AF in the pathophysiology of AF. First, we evaluated the pathological effects of sEVs derived from the peripheral blood of patients with persistent AF (AF-sEVs). AF-sEVs treatment reduced cell viability, caused abnormal Ca2+ handling, induced reactive oxygen species (ROS) production and led to increased CaMKII activation of non-paced and paced atrial cardiomyocytes. Next, we analyzed the miRNA profile of AF-sEVs to investigate which components of AF-sEVs promote arrhythmias, and we selected six miRNAs that correlated with CaMKII activation. qRT-PCR experiment identified that miR-30a-5p was significantly down-regulated in AF-sEVs, paced cardiomyocytes, and atrial tissues of patients with persistent AF. CaMKII was predicted by bioinformatics analysis as a miR-30a-5p target gene and validated by a dual luciferase reporter; hence, we evaluated the effects of miR-30a-5p on paced cardiomyocytes and validated miR-30a-5p as a pro-arrhythmic signature of AF-sEVs. Consequently, AF-sEVs-loaded with miR-30a-5p attenuated pacing-induced Ca2+-handling abnormalities, whereas AF-sEVs-loaded with anti-miR-30a-5p reversed the change in paced cardiomyocytes. Taken together, the regulation of CaMKII by miR-30a-5p revealed that miR-30a-5p is a major mediator for AF-sEVs-mediated AF pathogenesis. Accordingly, these findings suggest that sEVs derived from patients with persistent AF exacerbate arrhythmogenesis via miR-30a-5p., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Cardiac adipose tissue is a well-known risk factor for the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation, but its correlation with maze surgery remains unknown. The aim of this study was to investigate the correlation between the recurrence of AF and the adipose component of the left atrium (LA) in patients who underwent a modified Cox maze (CM) III procedure. We reviewed the pathology data of resected LA tissues from 115 patients, including the adipose tissue from CM-III procedures. The mean follow-up duration was 30.05 ± 23.96 months. The mean adipose tissue component in the AF recurrence group was 16.17% ± 14.32%, while in the non-recurrence group, it was 9.48% ± 10.79% ( p = 0.021), and the cut-off value for the adipose component for AF recurrence was 10% ( p = 0.010). The rates of freedom from AF recurrence at 1, 3, and 5 years were 84.8%, 68.8%, and 38.6%, respectively, in the high-adipose group (≥10%), and 96.3%, 89.7%, and 80.3%, respectively, in the low-adipose group (<10%; p = 0.002). A high adipose component (≥10%) in the LA is a significant risk factor for AF recurrence after CM-III procedures. Thus, it may be necessary to attempt to reduce the perioperative adipose portion of the cardiac tissue using a statin in a randomized study.

Various perivascular drug delivery techniques have been demonstrated for localized post-treatment of intimal hyperplasia: a vascular inflammatory response caused by endothelial damages. Although most perivascular devices have focused on controlling the delivery duration of anti-proliferation drug, the confined and unidirectional delivery of the drug to the target tissue has become increasingly important. In addition, careful attention should also be paid to the luminal stability and the adequate exchange of vascular protein or cell between the blood vessel and extravascular tissue to avoid any side effect from the long-term application of any perivascular device. Here, a highly flexible and porous silk fibroin microneedle wrap (Silk MN wrap) is proposed to directly inject antiproliferative drug to the anastomosis sites while ensuring sufficient vascular exchanges. Drug-embedded silk MNs were transfer-molded on a highly flexible and porous silk wrap. The enhanced cell compatibility, molecular permeability, and flexibility of silk MN wrap guaranteed the structural integrity of blood vessels. Silk wrap successfully supported the silk MNs and induced multiple MN penetration to the target tissue. Over 28 days, silk MN wrap significantly inhibited intimal hyperplasia with a 62.1% reduction in neointimal formation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host-plant associations, uncovering the widespread co-option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.

Background: This study aimed to evaluate the early outcomes of Perceval sutureless valves in the Korean population and to introduce a modified technique of guiding suture placement during valve deployment.Methods and Results:From December 2014 to April 2019, 121 patients (mean age: 74.7±6.2 years; 53.7% female) received a Perceval sutureless aortic valve replacement. To prevent conduction system injury, the depth of guiding suture placement (1 mm below the nadir of the annulus) was modified. All patients underwent echocardiographic evaluation at discharge and 6-12 months postoperatively, with a mean follow up of 13.7±11.2 months. Concomitant surgeries, such as coronary artery bypass grafting, and other valvular surgeries, were performed in 45.5% of cases. The mean aortic cross-clamp times for isolated and minimal procedures were 32.8±7.9, and 41.2±8.0 min, respectively. The overall transvalvular mean gradients were 13.1±3.8 mmHg at discharge and 11.5±4.7 mmHg at the last follow up. After modifying the guiding suture placement, permanent pacemaker implantation risk decreased from 9.9% to 2.5%. Cardiac-related mortality was 0.8%, with no patient developing valvular or paravalvular aortic regurgitation, valve thrombosis, or endocarditis., Conclusions: Perceval valve implantation provided a significant cardiac-related survival benefit with excellent early hemodynamic and clinical outcomes. Further research is needed to determine whether adjusting the implantation depth, such as modification of the guiding suture technique, can reduce the risk of permanent pacemaker implantation.

Background: The relationship between functional mitral stenosis (MS) after mitral valve (MV) repair and long-term clinical outcomes is not fully understood. Therefore, we reviewed an institutional series to identify the determinants of functional MS and its effect on long-term clinical outcomes after MV repair for degenerative mitral regurgitation., Methods: Between January 1990 and December 2015, 792 patients who underwent MV repair for degenerative mitral regurgitation were retrospectively enrolled and divided into 2 groups: functional MS (n = 192) (≥5 mm Hg mean diastolic pressure gradient across the MV) and nonfunctional MS (n = 600) (<5 mm Hg mean diastolic pressure gradient). Mean follow-up was 11.6 ± 5.8 years., Results: After propensity-score matching, patients' characteristics were comparable between groups (n = 192/group). At 20 years, the functional MS group had significantly lower rates of freedom from new-onset atrial fibrillation (73.0% ± 5.6% versus 93.2% ± 2.3%; P = .003), overall survival (72.1% ± 4.6% versus 85.6% ± 4.3%; P = .010), and freedom from MV reoperation (82.8% ± 4.1% versus 92.5% ± 4.2%; P = .019) than the nonfunctional group. The functional MS group also had a significantly greater postoperative left atrial volume index and tricuspid regurgitation grade. A small left ventricular end-diastolic dimension (hazard ratio = 0.975; 95% confidence interval, 0.955-0.996; P = .022) and annuloplasty ring (hazard ratio = 0.757; 95% confidence interval, 0.685-0.837; P < .001) were independent risk factors for functional MS., Conclusions: A small left ventricle and annuloplasty ring increased the risk for functional MS after MV repair and was associated with progressive left atrial enlargement and tricuspid regurgitation exacerbation. As a result, functional MS increased the risk for new-onset atrial fibrillation, MV reoperation, and decreased long-term survival., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The Trifecta valve has externally mounted leaflets; it differs from classic internally mounted valves (e.g., Carpentier-Edwards [C-E]). We evaluated post-implantation hemodynamics and clinical outcomes of these bioprostheses in small aortic annuli. From January 2015 to April 2019, 490 patients who underwent aortic valve replacement (AVR) were reviewed retrospectively. Altogether, 183 patients received 19 or 21 mm diameter C-E ( n = 121) or Trifecta ( n = 62) prostheses. To minimize confounding variables, we performed propensity-score matching analysis. The mean transvalvular pressure gradient (TVPG) was significantly lower in the Trifecta than in the C-E group at discharge (12.9 ± 4.8 vs. 15.0 ± 5.3 mmHg, p = 0.044). TVPG change over time was not significantly different between groups ( p = 0.357). Left ventricular mass index decreased postoperatively (reduction: C-E, 28.1%; Trifecta, 30.1%, p = 0.879). No late mortality, severe patient-prosthesis mismatch, moderate-to-severe paravalvular leakage, structural valve degeneration, or valve thromboses were observed. Freedom from valve-related events at 3 years were similar for C-E (97.9% ± 2.1%) and Trifecta (97.7% ± 2.2%) patients (log-rank p = 0.993). Bioprosthesis design for small annuli significantly affected TVPG immediately after AVR. However, hemodynamics over time and clinical outcomes did not differ between the two designs.

Background The objectives of the present study were (1) to evaluate the echocardiographic prognostic factors associated with improved left ventricular (LV) systolic function after aortic valve replacement, and (2) to compare the long-term outcomes after aortic valve replacement in chronic aortic regurgitation (AR) patients with or without LV dysfunction. Methods and Results A total of 280 patients who underwent aortic valve replacement because of chronic aortic regurgitation were studied. Patients with reduced LV systolic function (LV ejection fraction [LVEF] <50%; group reduced LVEF [rEF]; N=80) were compared with those with preserved LV systolic function (LVEF ≥50%; group preserved LVEF; N=200). Postoperative clinical outcomes, overall survival, and freedom from cardiac death were compared. Postoperative echocardiographic examinations were reviewed, and changes in echocardiographic parameters were analyzed. The parameters related to LVEF improvement or normalization were evaluated, and risk factors affecting long-term survival were identified. Follow-up was complete in 100% of patients, with a median follow-up of 104.8 months. Overall and cardiac mortality-free survival rates at postoperative 10 years were 80.1% and 92.9% and 87.3% and 97.2% in groups rEF and preserved LVEF, respectively ( P =0.036 and P =0.058, respectively). LVEF tended to decrease in the early postoperative period but improved thereafter in both groups. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio was a parameter of postoperative improvement or normalization of LVEF in all patients (area under the curve, 0.719; P =0.003) and in group rEF patients (area under the curve, 0.726; P =0.011) with a cutoff value of 12.73. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio also was the parameter of overall survival in all patients (hazard ratio [HR], 1.08; P =0.001) and in group rEF patients (HR, 1.08; P =0.005). Conclusions Long-term outcomes and survival after aortic valve replacement were related to preoperative LV function in patients with chronic aortic regurgitation. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio was correlated with the postoperative improvement or normalization of LVEF and long-term survival, especially in group rEF patients.

Background: The extracorporeal ventricular assist device (e-VAD) system is designed for left ventricular support using a permanent life support console. This study aimed to determine the impact of temporary e-VAD implantation bridging on posttransplant outcomes., Methods: We reviewed the clinical records of 6 patients with the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1, awaiting heart transplantation, who were provided with temporary e-VAD from 2018 to 2019. The circuit comprised a single centrifugal pump without an oxygenator. The e-VAD inflow cannula was inserted into the apex of the left ventricle, and the outflow cannula was positioned in the ascending aorta. The median follow-up duration was 8.4±6.9 months., Results: After e-VAD implantation, lactate dehydrogenase levels significantly decreased, and Sequential Organ Failure Assessment scores significantly improved. Bedside rehabilitation was possible in 5 patients. After a mean e-VAD support duration of 14.5±17.3 days, all patients were successfully bridged to transplantation. After transplantation, 5 patients survived for at least 6 months., Conclusion: e-VAD may reverse end-organ dysfunction and improve outcomes in INTERMACS I heart transplant patients.

Objective: This study aimed to evaluate the changes in postoperative aortic regurgitation (AR) and determine the predictors of significant AR and root reoperation after ascending aortic replacement (AAR) in patients with acute type A aortic dissection., Methods: From January 1995 to December 2017, 271 consecutive patients underwent valve/root-preserving AAR (n = 225) and root replacement (n = 46). AR grade trend over time was analyzed by the ordinal mixed-effects model. Significant AR was defined as AR grade ≥3+ during the follow-up period. Predischarge and follow-up echocardiograms were obtained in 95.6% and 88.8% of enrolled patients, respectively., Results: At predischarge, postoperative ≥2+ AR was present in 20 (9.3%) and 1 (2.3%) patients in the AAR and root replacement groups, respectively. With increasing time after surgery, the grade of AR increased. At 10 years, 4.6% of patients had developed 3+ or 4+ AR. Considering death as the competing risk, the 10-year cumulative incidence of significant AR was significantly higher in the AAR than in the root replacement group (12.3% vs 2.2%; P = .047). The risk of root reoperation at 10 years was not different between the groups (P = .118). On Cox analysis, preoperative ≥3+ AR (P = .002), postoperative ≥2+ AR (P = .040), and false to true lumen ratio (P = .005) were associated predictors of significant AR., Conclusions: Although valve/root-preserving AAR demonstrated reasonable long-term outcomes when compared with root replacement, preoperative ≥3+ AR, postoperative ≥2+ AR, and high false to true lumen ratio significantly increased the risk of significant AR. Therefore, careful echocardiographic surveillance may be warranted in patients with postoperative ≥2+ AR and small true lumen., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We compared the long-term outcomes and difference in dilatation rates of the ascending aorta after aortic valve (AV) replacement (AVR) between bicuspid and tricuspid AV patients, and evaluated risk factors associated with ascending aorta dilatation and aortic events during the follow-up. Of 1,127 patients who underwent AVR from 1995 to 2015, 259 patients with a dilated ascending aorta (≥40 mm in diameter) were included. The patients were divided into those with bicuspid (group bicuspid aortic valve [BAV], n = 105) and with tricuspid (group tricuspid aortic valve [TAV], n = 154) AV, and a propensity score-matched analysis was performed to match 98 patients in each group. The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. Risk factors for ascending aorta dilatation, mortality, and aortic events were identified. Follow-up was completed in 100% of patients with a median follow-up duration of 106.1 [68.8, 163.0] months. The early clinical outcomes and dilation rate of the ascending aorta were similar between the groups. Overall survivals up to 15 years postoperatively were similar between groups BAV and TAV (p = 0.223). Aortic events occurred in 6 patients (groups BAV vs TAV, 2 vs 4;p = 0.678). Preoperative ascending aorta diameter showed a linear relationship with the dilatation rate of ascending aorta (p <0.001) and was related to progressive aortic dilatation and aortic events (odds ratio: 1.25, p <0.001 and hazard ratio = 1.56, p <0.001, respectively). In conclusion, the long-term outcomes and ascending aorta dilatation rate were similar between the BAV and TAV patients up to 15 years after AVR. Bicuspid AV was not a risk factor of mortality or aortic events., Competing Interests: Conflict of Interests None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The role of a reentry tear in the descending thoracic aorta (DTA) after repair of acute aortic dissection is not well known. We therefore investigated the impact of reentry tear location on late aorta reintervention and the aortic expansion rate after open repair of acute type I aortic dissection., Methods: We analyzed 309 nonsyndromic acute type I aortic dissection patients who were treated with a repair to the proximal aorta between 1994 and 2017. The locations of reentry tears, identified with predischarge computed tomography, were the proximal DTA in 119 patients (38.5%), distal DTA in 78 (25.2%), and abdominal aorta in 129 (41.7%). Patients who had a proximal DTA reentry tear were defined as the PDR group (119 [38.5%]), and the others were defined as the non-PDR group (190 [61.5%])., Results: The 15-year freedom from aorta reintervention was significantly lower in the PDR group (51.5% ± 0.7% vs 90.4% ± 4.4%, P < .001). The aortic expansion rates of the proximal DTA (7.6 ± 16.1 mm/y vs 0.1 ± 2.5 mm/y, P < .001) and distal DTA (6.8 ± 15.5 mm/y vs 0.3 ± 3.1 mm/y, P < .001) were significantly higher in the PDR group. The 15-year freedom from significant aortic expansion was significantly lower in the PDR group (34.6% ± 6.9% vs 83.6% ± 7.9%, P < .001). Multivariate analysis showed that a proximal DTA reentry tear was an independent risk factor for aorta reintervention (hazard ratio, 4.955; 95% confidence interval, 1.691-14.523; P = .004) and significant aortic expansion (HR, 4.214; 95% CI, 1.691-10.498; P = .002)., Conclusions: A proximally located DTA reentry tear was associated with an increased risk of late aorta reintervention and distal aortic dilatation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1084). The authors have no conflicts of interest to declare.

Artificial vessels capable of long-term patency are essential clinical tools in vascular surgery that involves small vessels. On-going attempts to develop artificial vessels that complements restenosis have not been entirely successful. Here, we report on the fabrication of small-sized artificial vessels using a three-dimensional bio-printer. The fabrication employed biodegradable polycaprolactone and autologous MSCs harvested from the bone-marrow of canines. The MSCs were cultured and differentiated into endothelial-like cells. After confirming differentiation, artificial vessels comprising three-layers were constructed and implanted into the arteries of canines. The autologous MSCs printed on artificial vessels (cell-derived group) maintained a 64.3% patency (9 of 14 grafts) compared with artificial vessels without cells (control group, 54.5% patency (6 of 11 grafts)). The cell-derived vessels (61.9 cells/mm 2 ± 14.3) had more endothelial cells on their inner surfaces than the control vessels (21 cells/mm 2 ± 11.3). Moreover, the control vessels showed acute inflammation on the porous structures of the implanted artificial vessels, whereas the cell-derived vessels exhibited fibrinous clots with little to no inflammation. We concluded that the minimal rejection of these artificial vessels by the immune system was due to the use of autologous MSCs. We anticipate that this study will be of value in the field of tissue-engineering in clinical practice.

Background: Many variables may affect the hemodynamic performance of the aortic valve prosthesis, and suture technique remains an important factor for determining maximum valve performance. The objective of this study was to determine the suture technique that produces better hemodynamic performance for aortic valve replacement (AVR)., Methods: Patients who underwent AVR between January 2015 and September 2018 in our institution were analyzed. We compared the preoperative clinical information and 1-year postoperative hemodynamic data of interrupted pledget mattress sutures (pledgeted group), interrupted nonpledget mattress sutures (nonpledgeted group), and figure-of-8 nonpledget sutures (figure-of-eight group). We compared the incidence of prosthesis-patient mismatch (PPM) and cardiac adverse events among the groups and subanalyzed the PPM rate in a small aortic annulus (18 to 21 mm)., Results: A total of 439 patients underwent AVR (pledgeted, n = 212; nonpledgeted, n = 122; figure-of-eight, n = 105). The groups were similar in age (P = .359), sex (P = .055), underlying disease, and valve pathology. There was no difference in inhospital mortality or cardiac adverse events in each suture group (P = .282). The nonpledgeted suture had significantly lower moderate (P < .01) and severe PPM rates (P = .01) in patients with a small aortic annulus (18 to 21 mm)., Conclusions: The interrupted nonpledget mattress suture offers complete supraannular implantation, which reduces the incidence of PPM and results in better hemodynamic improvement after small-size AVR., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of axillary artery cannulation for early embolic stroke and operative mortality, we retrospectively compared the outcomes between patients with or without axillary artery cannulation during open aortic arch repair with circulatory arrest., Methods: Between January 2004 and December 2017, 468 patients underwent open aortic arch repair with circulatory arrest using antegrade cerebral perfusion and were divided into 2 groups according to the site of arterial cannulation: the axillary artery (axillary group, n = 352) or another site (nonaxillary group, n = 116) groups. Embolic stroke was defined as a physician-diagnosed new postoperative neurologic deficit lasting more than 72 hours, generally confirmed by computed tomography or magnetic resonance imaging., Results: After propensity score matching, the patients' characteristics were comparable between the groups (n = 116 in each). The incidences of acute type A dissection, aortic rupture, shock, or emergency operation were similar between groups. The incidence of early embolic stroke was significantly lower in axillary group (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046). Also, 30-day mortality (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046) and in-hospital mortality (n = 3 [2.6%] vs n = 11 [9.5%]; P = .027) occurred significantly lower in the axillary group., Conclusions: Axillary artery cannulation reduced the early embolic stroke and early mortality after open arch repair with circulatory arrest. Axillary artery cannulation as the arterial cannulation site during open arch repair with circulatory arrest may be helpful in preventing embolic stroke and reducing early mortality., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: There seem to be modifiable components of diabetes in terms of glycemic control to improve surgical outcome. The aim of the study was to evaluate impact of preoperative glycated hemoglobin (HbA1c) level in patients with diabetes mellitus undergoing off-pump coronary bypass (OPCAB) on perioperative glycemic variability and short-term outcome., Methods: Medical records of 703 patients with diabetes mellitus who underwent OPCAB from 2005 to 2017 were reviewed. The perioperative goal of glycemic control was <180 mg/dL. Patients were divided into 2 groups according to HbA1c level (<7.0% or ≥7.0%). Glycemic variability during surgery and up to 24 hours after surgery was assessed by coefficient of variation (CV). Primary outcome was defined as composite of postoperative permanent stroke, prolonged ventilation, deep sternal wound infection, renal failure, reoperation, and 30-day mortality., Results: Incidence of composite of postoperative morbidity and mortality endpoints was greater in patients with HbA1c ≥7.0% (21% vs 15%, P = .041). Perioperative time-weighted average glucose concentration was also greater in patients with HbA1c ≥7.0%, whereas the CV did not show any difference. Multivariable logistic regression analysis revealed that congestive heart failure, chronic kidney disease, moderate mitral regurgitation or greater, preoperative hemoglobin level, and preoperative HbA1c ≥7.0% were independently associated with composite of postoperative morbidity and mortality, but perioperative CV and time-weighted average glucose ≥200 mg/dL were not., Conclusions: Increased preoperative HbA1c (≥7.0%) level reflecting long-term glycemic control seems to exert an adverse influence on outcome, whereas the influence of perioperative glycemic variables appear to be abrogated using a target glucose level of <180 mg/dL in patients with diabetes mellitus undergoing OPCAB., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Long-term outcomes of mitral valve replacement (MVR) recipients with pulmonary hypertension (PH) remain unclear. We determined the effect of concomitant PH on the clinical outcomes and late-onset progression of tricuspid regurgitation (TR) after MVR for rheumatic mitral stenosis., Methods: We retrospectively reviewed 394 patients who underwent MVR between January 2000 and December 2013. PH was defined as systolic pulmonary arterial pressure (sPAP) >50 mm Hg. Changes in echocardiographic parameters (preoperative to postoperative), TR progression (grade ≥ II), and long-term survival were evaluated according to the presence of PH at MVR (non-PH, n = 322; PH, n = 72)., Results: The 10-year overall survival rate was significantly lower in the PH group (79.7% vs 90.7%, P = .04), whereas the rate of freedom from TR progression was similar between groups (76.9% vs 80.5%, P = .373). High preoperative sPAP and right ventricular systolic pressure (RVSP) did not affect TR progression. However, substantial postoperative reductions in sPAP and RVSP protected against TR progression (hazard ratio [95% confidence interval], 0.966 [0.942-0.991], P = .008, and 0.973 [0.960-0.986], P < .001, respectively). The 10-year rate of freedom from TR progression was significantly higher in patients with substantial sPAP and RVSP reductions (sPAP, 84.2% vs 70.6%, P = .003; RVSP, 84.9% vs 71.0%, P < .001)., Conclusions: Although concomitant PH at MVR is associated with poor long-term survival, adequate sPAP and RVSP reduction can prevent TR progression even in patients with severe PH preoperatively. Therefore, we suggest careful monitoring of PAP and RVSP after MVR and should make an effort to reduce postoperative PAP., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The long-term outcomes of aortic wrapping in patients with ascending aortic aneurysms, which are rare, but can be fatal, remain poorly understood. This retrospective study analyzed the outcomes of aortic diameter, including aortic root, ascending aorta, and proximal arch diameters, after aortic wrapping during aortic valve replacement surgery., Materials and Methods: Ninety-six patients with ascending aortic dilation of 40-55 mm who underwent aortic wrapping during aortic valve replacement were selected for this study. Aortic diameter was measured at three levels perioperatively and at follow-up (median time of 9.1±4.2 years). A linear mixed-effects model was used to analyze aortic diameter expansion., Results: Freedom from adverse aortic events (aortic dissection or rupture, reoperation, or sudden death) at 10 years was 97.9%. No significant dilation at the level of the sinuses of Valsalva (0.069 mm/year, p =0.524) or ascending aorta (0.152 mm/year, p =0.124) was observed. Significant dilation occurred at the proximal aortic arch (0.343 mm/year, p =0.006). Subgroup analysis with a multivariable linear mixed model identified initial ascending aortic diameter to be a significant predictor of proximal arch dilation ( p =0.032). Receiver operating characteristic curve analysis revealed that the cut-off for the prediction of proximal arch redilation was an initial mid-ascending aortic diameter of 47.0 mm (area under the curve 0.747, 90% confidence interval 0.613-0.881, p =0.023)., Conclusion: Aortic wrapping could be considered as a safe and long-term therapeutic option. Redilation of the proximal arch should be carefully observed during long-term follow-up., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Objective: Although hybrid arch repair has gained widespread application as an alternative option for high-risk patients, concerns about its long-term durability remain an important issue. The aim of this study was to investigate late complications after hybrid arch repair., Methods: From January 2002 to December 2017, hybrid arch repair was performed in 65 patients with aortic arch disease (median age, 66.1 years; range, 41-86 years). Hybrid arch repair was defined as debranching involving at least one supra-aortic vessel bypass and simultaneous or staged endovascular thoracic stent grafting. We retrospectively analyzed late complications including reintervention, open conversion, and aortic-related death. The median follow-up period was 60.1 months (range, 1-170 months)., Results: The in-hospital mortality rate was 6% (4/65). Except for early death (n = 4) and early open conversion (n = 2), late complications were observed in 25 patients (25/59 [42%]). The median time interval between the initial procedure and late complication was 36.6 months (range, 1-92 months). Late complications included delayed type I endoleak (n = 8), distal stent-induced new entry (n = 3), stent migration (n = 3), retrograde type A dissection (n = 2), aortopulmonary fistula (n = 2), aortoesophageal fistula (n = 1), stent fracture (n = 1), infection (n = 1), and sudden death (n = 4). Six of these patients (10%) underwent late open conversion. The overall survival rates at 3 years and 6 years were 71.1 ± 7.4% and 57.2 ± 11.3%, respectively. The aortic event-free rates at 3 years and 6 years were 52.1 ± 7.3% and 39.4 ± 10.3%, respectively., Conclusions: Late complications in hybrid arch repair occurred in a substantial proportion of patients during midterm follow-up. Regardless of zone type, the incidence of late complications was relatively high. This study suggests that timely reintervention and open conversion are important for rescuing patients, but repeated reinterventions and conservative strategies are not recommended. Aggressive management and life-long surveillance after hybrid arch repair are mandatory for better outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of the study was to examine the effects of statin treatment on calcification in commercially available bioprosthetic heart valves., Methods: Twenty Sprague-Dawley rats were fed a high-fat diet to induce hypercholesterolemia during 4 weeks. They were randomly divided into 2 groups according to statin intake (control, n = 10: high-fat diet/statin; n = 10: high-fat diet with statin). Four commercially available tissue valve (Magna Perimount, Carpentier-Edwards, Irvine, Calif; Hancock, Medtronic, Minneapolis, Minn; Mitroflow, LivaNova, London, England; and Trifecta, St Jude Medical, St Paul, Minn) cusp samples (total 320) were implanted in rat dorsal subcutis at 4 weeks. After implantation, rosuvastatin was administered daily to the statin group. The cusps were explanted at 12 weeks, and calcium levels were determined by atomic absorption spectroscopy. Western blotting, histologic, and immunohistochemical analyses were conducted to identify the anticalcification mechanism of the statin., Results: The mean calcium level in the control group was significantly higher than in the statin group (P < .01) for all tissue valves (Magna Perimount: 2.67 ± 0.26 mg/g vs 1.31 ± 0.40 mg/g; Hancock: 2.70 ± 0.57 mg/g vs 1.53 ± 0.34 mg/g; Mitroflow: 2.39 ± 0.71 mg/g vs 1.26 ± 0.38 mg/g; Trifecta: 2.54 ± 0.42 mg/g vs 1.63 ± 0.72 mg/g). Inflammatory cell infiltration and interleukin-6 and bone morphogenetic protein 2 expressions were significantly reduced in the statin group., Conclusions: Statin treatment significantly attenuated bioprosthetic heart valve calcification associated with decreasing the levels of interleukin-6 and bone morphogenetic protein 2. Thus, statin treatment might be helpful for the longevity of bioprosthetic heart valves., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: With the increasing use of endovascular aortic repair, open repair after aortic stent grafting is of increasing interest. We retrospectively reviewed cases of late open conversion for complications after thoracic endovascular aortic repair (TEVAR)., Methods: TEVAR due to aortic aneurysm and dissection was performed in 538 patients between 1994 and 2017. A total of 33 patients, including 4 patients referred from other centers, required late conversion to open repair; 14 (42.4%) patients required circulatory arrest for aortic arch involvement. The mean interval to open conversion after TEVAR was 33.9 months (range, 1-123 months). Demographics of the patients, reason for conversion, surgical techniques, surgical outcomes, and survival were reviewed., Results: Indications for late open conversion included type I endoleak (14), stent graft-induced new entry intimal tear (6), retrograde type A dissection (4), stent migration and fracture (3), stent graft infection (3), sac enlargement without endoleak (1), aortopulmonary fistula (1), and stent implantation failure (1). Hospital mortality was 9.1% (3/33). All occurred in the patients with arch involvement. The patients had several major morbidities; six patients (18.1%) had pulmonary complications, two (6.1%) suffered a stroke, one (3.0%) experienced paraplegia, and one (3.0%) had renal failure. Overall survival rates at 1 year, 5 years, and 10 years were 84.5% ± 6.4%, 74.5% ± 8.7%, and 67.1% ± 10.1%, respectively. The arch involvement group (48.1% ± 15.7%) had significantly worse 10-year survival than the no arch involvement group (86.1% ± 9.4%; P = .048)., Conclusions: Despite the complexity of TEVAR, open conversion due to late complications can be performed successfully with acceptable results. However, cases involving the aortic arch have relatively worse outcomes. Lifelong surveillance is mandatory, and early decision-making about open conversion before the development of a complicated aortic arch lesion is suggested to achieve better outcomes., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Severe aortic atherosclerosis is a risk factor for stroke during coronary artery bypass grafting (CABG). The purpose of this study was to evaluate the incidence of postoperative neurologic complications after off-pump CABG (OPCAB) with a proximal seal system (Heartstring).From January 2011 to December 2014, 729 patients underwent isolated OPCAB. The cohort was divided into two groups (Heartstring [HS] and aortic no-touch [NT]). The severity of aortic atherosclerosis (Katz grade) was evaluated by intraoperative epiaortic ultrasonography (EUS). The primary endpoints were postoperative neurologic complications (early stroke and minor events (delirium, transient ischemic attack, and syncope) ), and the secondary endpoints were late major adverse cardiac and cerebrovascular events (MACCEs) and death.The mean age of all patients was 65.1 ± 9.5 years, and a severe Katz grade (IV or V) was demonstrated to be an independent risk factor of long-term mortality (HR 3.53; 95% CI 1.06-11.75; P = 0.04) and MACCEs (HR 2.41; 95% CI 1.19-4.92; P = 0.02), but no significant differences were found for early stroke (0.9% versus 1.7%; P = 0.53) and minor neurologic complications (14.6% versus 9.9%; P = 0.05) between the groups regardless of the Katz grade. The 5-year overall survival rate did not differ significantly between the groups (90.9% versus 87.6%; P = 0.61).Although a higher Katz grade was identified as an independent risk factor of death and MACCEs, the HS group was not inferior in terms of neurologic complications regardless of the Katz grade. Therefore, the Heartstring system might be safely and efficiently used with EUS to decrease the incidence of neurologic complications.

Background: It is unclear at present whether conventional open repair or a hybrid technique is preferential in the treatment of aortic arch diseases. Our intent was to compare early and long-term outcomes of both therapeutic strategies., Methods: Between January 2002 and December 2017, 238 patients eligible for total arch replacement (TAR; 174) or hybrid arch repair (HAR; 64) qualified for study. A retrospective analysis of clinical outcomes was undertaken, with propensity matching (48 pairs). Mean follow-up duration was 60.2 months., Results: In-hospital mortality rates were 4.6% (8 of 174 patients) and 6.3% (4 of 64 patients) in the TAR and HAR groups, respectively (p = 0.739). The TAR group displayed a lower incidence of permanent stroke (2.9%, 5 of 174 patients) by comparison (HAR: 12.5%, 8 of 64 patients; p = 0.004). Overall survival rates at 5 and 10 years differed significantly by group (TAR: 87.0% ± 5.5% and 81.9% ± 4.8%, respectively; HAR: 69.5% ± 7.4% and 40.8% ± 11.1%, respectively; p = 0.003). After propensity matching, in-hospital mortality (4.2% versus 4.2%, p > 0.99) and patient morbidities showed no statistically significant group differences. For patients undergoing HAR, a tendency for permanent stroke (14.5% versus 2.1%, p = 0.070) was evident. In the TAR (versus HAR) group, 10-year overall survival (74.7% versus 42.6%, p = 0.043) and reintervention-free (93.2% versus 34.0%, p < 0.001) rates were significantly better., Conclusions: In the treatment of aortic arch diseases, HAR showed equivalent short-term outcomes compared with TAR but was limited regarding long-term outcomes beyond 5 years after the procedure. Conventional TAR remains the gold standard of therapy, and our findings suggest that the hybrid approach should be reserved for strictly selected patients with significant comorbidities., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is no consensus as to whether a median approach or a lateral approach is better for distal aortic arch aneurysms with distal extensions. The aim of this study was to compare clinical outcomes of these two approaches for distal aortic arch aneurysms with distal extensions., Methods: From January 2001 to December 2017, 212 consecutive patients with distal aortic arch aneurysms with distal extensions underwent surgery using different approaches: hemiarch and descending thoracic aneurysm replacement through thoracotomy (group 1, n = 91); and total arch and descending thoracic aneurysm replacement through sternotomy (group 2, n = 121). Early and late outcomes were compared using scores and inverse probability of treatment adjustments to reduce treatment selection bias., Results: The in-hospital mortality was 9.89% (9 of 91) in the thoracotomy group and 2.48% (3 of 121) in the sternotomy group (p = 0.02). The sternotomy group had a lower incidence of permanent stroke (2.48%, 3 of 121) compared with the thoracotomy group (10.99%, 10 of 91, p = 0.01). After adjustment, patients who underwent thoracotomy were at a greater risk of hospital mortality (odds ratio 5.0, p = 0.01), permanent stroke (odds ratio 6.83, p < 0.01), and pneumonia (odds ratio 2.99, p = 0.04), compared with patients who underwent sternotomy. The overall survival at 10 years was 69.8% ± 7.0% for the thoracotomy group and 83.0% ± 5.0% for the sternotomy group (unadjusted p = 0.049, adjusted p = 0.034)., Conclusions: The sternotomy approach showed better outcomes in terms of operative mortality, stroke, and pneumonia, as well as long-term survival compared with the thoracotomy approach. These results suggested that the sternotomy approach was more appropriate for patients with distal aortic arch aneurysms with distal extensions., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Various treatment methods for tracheal defects have been attempted, such as artificial implants, allografts, autogenous grafts, and tissue engineering; however, no perfect method has been established. We attempted to create an effective artificial trachea via a tissue engineering method using 3D bio-printing. A multi-layered scaffold was fabricated using a 3D printer. Polycaprolactone (PCL) and hydrogel were used with nasal epithelial and auricular cartilage cells in the printing process. An artificial trachea was transplanted into 15 rabbits and a PCL scaffold without the addition of cells was transplanted into 6 rabbits (controls). All animals were followed up with radiography, CT, and endoscopy at 3, 6, and 12 months. In the control group, 3 out of 6 rabbits died from respiratory symptoms. Surviving rabbits in control group had narrowed tracheas due to the formation of granulation tissue and absence of epithelium regeneration. In the experimental group, 13 of 15 animals survived, and the histologic examination confirmed the regeneration of epithelial cells. Neonatal cartilage was also confirmed at 6 and 12 months. Our artificial trachea was effective in the regeneration of respiratory epithelium, but not in cartilage regeneration. Additional studies are needed to promote cartilage regeneration and improve implant stability.