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We examined the safety and efficacy of del Nido cardioplegic solution compared with histidine-tryptophan-ketoglutarate cardioplegic solution in minimally invasive cardiac surgery.Patients who underwent minimally invasive cardiac surgery using del Nido or histidine-tryptophan-ketoglutarate from 2015 to 2019 were enrolled. Various clinical outcomes were compared between the groups. Postoperative laboratory findings including the levels of electrolytes, cardiac enzymes (creatine kinase-MB and troponin I), and serial blood lactate were also measured and compared. Based on 28 baseline covariates, propensity score matching was performed to reduce selection bias.Among 766 patients, del Nido and histidine-tryptophan-ketoglutarate were used in 330 patients (43.1%) and 436 patients (56.9%), respectively. There were no significant intergroup differences in postoperative clinical outcomes and early adverse outcomes among 228 pairs of propensity score-matched patients. Immediate postoperative sodium levels were within the normal range in both groups without a significant difference (P = .50). However, peak creatine kinase-MB (median, 31.9 vs 37.7 ng/mL, P = .026) and troponin I (6.9 vs 9.1 ng/mL, P = .014) levels were significantly lower in the del Nido group. Linear regression analysis revealed a significant association between the peak cardiac enzyme levels and the cardiac ischemic time depending on the cardioplegia type, with lower cardiac isoenzymes for del Nido over histidine-tryptophan-ketoglutarate (P .001) until the crossover point at the cardiac ischemic time over 100 minutes.In comparison with histidine-tryptophan-ketoglutarate solution, del Nido solution seems to have acceptable safety and efficacy with good myocardial protection in minimally invasive cardiac surgery. Further studies focusing on complex surgeries requiring longer cardiac ischemic time are needed.

Background While several randomized trials have shown conflicting results regarding the comparative effectiveness of on- and off-pump coronary arterial bypass grafting (CABG), research on long-term outcomes in large-scale, real-world clinical settings are limited. We sought to examine the comparative effectiveness of on- and off-pump CABG in a real-world clinical setting. Methods Using the nationwide claims database of the Korean National Health Insurance Service, we identified patients who underwent isolated CABG from 2004 to 2013. Propensity-score matching with multivariable adjustment was used to assemble a cohort of patients with similar baseline characteristics. Results Among 23,828 patients, 12,639 in the off-pump (53.0%) and 11,189 in the on-pump (47.0%) groups were enrolled. After matching, 6,483 pairs were included in the final analysis. At 30 days, there was no significant difference in adjusted mortality between the off- and on-pump groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.87-1.16). During long-term follow-up (100% complete; median 5.3yrs, maximum 13.2yrs), however, off-pump CABG was associated with a higher risk of mortality than on-pump CABG (HR, 1.09; 95% CI, 1.03-1.15). The risks of myocardial infarction (MI) (HR, 1.3; 95% CI, 1.16-1.45) and repeat revascularization (HR, 1.50; 95% CI, 1.37-1.63) were also significantly higher in the off-pump CABG group than in the on-pump CABG group, while the stroke risk was similar inter-groups (HR, 0.99; 95% CI, 0.87-1.13). Conclusions In this contemporary, nationwide, clinical practice claim registry, off-pump CABG was associated with higher long-term risks of mortality, MI, and repeat revascularization than on-pump CABG.

The benefit of avoiding lifelong anticoagulation therapy in patients with bioprosthetic heart valve implantation may potentially be offset by atrial fibrillation (AF); however, clinical impact of surgical AF ablation in such patients remains controversial. We enrolled 426 patients (aged 72.0 ± 7.8 years) with AF who underwent left-side valve replacement with bioprostheses between 2001 and 2018. Of these, 297 underwent concomitant surgical ablation (ablation group) and 129 underwent valve replacement alone (non-ablation group). Clinical outcomes were compared, and mortality was considered as a competing risk factor against valve-related complications. Inverse-probability weighting (IPTW) was adopted to reduce selection bias. The ablation group had lower baseline risk profiles than the non-ablation group. In crude analysis, early mortality rates were 3.4% and 7.0% in the ablation and non-ablation groups, respectively (P = 0.104). During follow-up (1521.9 patient-years), the ablation group showed lower AF-recurrence (P0.001) and anticoagulant medication rate (P = 0.021), and lower overall mortality risk (subdistribution hazard ratio [SHR], 0.63; 95% confidence interval [CI], 0.42-0.94), but higher risk of permanent pacemaker implantation (SHR, 4.67; 95% CI, 1.36-16.05). No significant difference in the risk of stroke (SHR, 1.27; 95% CI, 0.55-2.95) was observed between the groups. After baseline IPTW-adjustment, findings of the clinical outcomes were analogous to those from crude analyses. In patients undergoing bioprosthetic valve replacement, the addition of surgical ablation was associated with improved rhythm outcomes and survival but at the expense of a higher risk of pacemaker implantation. The underlying mechanism of improved survival by AF ablation needs further investigation.

Enlarged left atrium (LA) is a risk factor for ablation failure after atrial fibrillation (AF) surgery. It predisposes patients to thromboembolic events, even in successful ablation; therefore, concomitant resection of the LA wall during surgical ablation was introduced. This study examined the clinical impacts of LA reduction in patients undergoing concomitant ablation for AF. This study enrolled 1484 patients with enlarged LA (≥50 mm) who underwent surgical AF ablation during major cardiac surgery between January 2001 and August 2018. Among them, 876 (59%) patients underwent concomitant LA reduction (Reduction group), whereas in the remaining 608 (41%), the LA wall was unresected (Preservation group). The primary outcome of interest was overall stroke. The secondary outcomes were overall mortality, late recurrence of AF, early postoperative complications and postoperative echocardiographic parameters. Outcomes were compared after adjusting baseline characteristics with inverse probability of treatment weighting (IPTW) using propensity score. The median follow-up was 60.1 months. After IPTW adjustment, long-term mortality (P = 0.250) and AF-free rates (P = 0.196) did not significantly differ between groups. However, the Reduction group showed a decreased risk of stroke (hazard ratio 0.54; 95% confidence interval 0.32-0.90; P = 0.018). Early postoperative complications rate such as mortality or reoperation for bleeding, was not significantly different between the 2 groups. The Reduction group showed smaller LA diameter (50.6 ± 8.0 mm vs 53.6 ± 8.9 mm; P0.001) on follow-up echocardiography. LA reduction effectively decreased LA size and appeared to decrease the stroke risk in patients with enlarged LA undergoing ablation for AF.

OBJECTIVES Right mini-thoracotomy approach may enhance the visualization of mitral valve (MV) visualization during redo MV surgery, thereby minimizing the risk of reoperative median sternotomy. We described the clinical outcomes of redo MV surgery by mini-thoracotomy and full-sternotomy approach. METHODS Of 730 consecutive adult patients who underwent redo MV surgery between 2002 and 2018 at our institution, we identified 380 patients (age: 56.0 [14.8] years) after excluding those who underwent concomitant aortic valve or coronary artery surgeries. RESULTS The clinical outcomes in patients who underwent mini-thoracotomy (MINI group; n = 168) and full-sternotomy (STERN group; n = 218) were described. The early and overall mortality in the MINI group was 4.3% (7/162) and 17.3% (28/162), with the rates of early major complications as follows: low cardiac output syndrome, 5.6% (9/162); early stroke, 6.8% (11/162); new-onset dialysis, 6.2% (10/162); prolonged ventilation, 15.4% (25/162); and postoperative bleeding requiring exploration, 7.4% (12/162). In the STERN group, the early mortality was 11.0% (24/218), whereas the risk of low cardiac output syndrome, early stroke, new-onset dialysis, prolonged ventilation, and postoperative bleeding was 12.4% (27/218), 14.2% (31/218), 17.0% (37/218), 33.0% (72/218), and 10.1% (22/218), respectively. The duration of intensive care unit and hospital stay was 2.0 [range 1.0, 3.0] and 8.0 [6.0, 13.0], respectively, in the MINI group and 3.0 [2.0, 7.0] and 14.0 [8.0, 29.0], respectively, in the STERN group. CONCLUSIONS Mini-thoracotomy may be a viable alternative to conventional sternotomy for redo MV surgery.

OBJECTIVES Complications like complete atrioventricular block (CAVB) and paravalvular leakage (PVL) following rapid deployment aortic valve (AV) replacement (RDAVR) remain unresolved. Selecting an optimal size of the valve might be important to minimize the incidence of these complications. We sought to determine the impact of prosthesis size relative to the anatomic profile of the AV on the occurrence of CAVB or PVL after RDAVR. METHODS Preoperative computed tomographic (CT) images were evaluated in patients receiving RDAVR (INTUITY ELITE) between February 2016 and December 2019. The occurrence of CAVB requiring permanent pacemaker implantation and PVL (≥ mild) was evaluated. The relative size of implants against the cross-sectional dimensions of recipients’ AV annulus and left ventricular outflow tract (LVOT) were calculated. RESULTS Among 187 eligible patients, CAVB and PVL (≥ mild) occurred in 12 (6.4%) and 11 patients (5.9%), respectively. CAVB was associated with oversized RDAVR (RDAVR frame width minus average diameter of LVOT calculated from the cross-sectional area [ΔLVOTarea]: odds ratio, 2.05; 95% confidence interval, 1.28–3.30): this was with an area under the curve of 0.78 (P = 0.005). The projected probability of CAVB was CONCLUSIONS CT parameters of the AV annulus and LVOT are highly reliable in the prediction of CAVB or PVL after RDAVR. Our data might justify CT-based sizing of prosthesis for RDAVR.

The purpose of this study was to evaluate whether bicuspid anatomy affects the discrepancy between CT-derived annular size and intraoperative size. We retrospectively analyzed annular measurements in 667 patients who underwent surgical aortic valve replacement (AVR). Preoperative CT measurements of the aortic annulus were compared to surgically implanted valve sizes. To evaluate whether the bicuspid valve affects the differences between CT annulus diameter and surgical AVR size, patients with diameter larger by > 10% (CT-Lg group) on CT, compared to surgical AVR size, were compared with those having size difference p p p p

Background: In thoracoabdominal aortic aneurysm repair, repairing the visceral and segmental arteries is challenging. Although there is a pre-hand-sewn and multi-branched graft based on the conventional image-based technique, it has shortcomings in precisely positioning and directing the visceral and segmental arteries. Methods: We introduce two new reconstruction techniques using patient-specific 3D-printed graft reconstruction guides: 1) model-based technique that presents the projected aortic graft, visualizing the main aortic body and its major branches and 2) guide-based technique in which the branching vessels in the visualization model are replaced by marking points identifiable by tactile sense. The graft reconstruction guides cover the segmentation, design, fabrication, post-processing, and clinical application of open surgical repair of thoracoabdominal aneurysm, and proved to be efficient for accurately reconstructing customized grafts. Findings: This study is demonstrated to the effectiveness and efficiency by evaluating conventional and new techniques with digital model. The accuracy, reproducibility, and satisfaction of the two new techniques were higher than that of the conventional technique, and the marking time requirement for graft reconstruction was reduced. Interpretation: The two new reconstruction techniques have the potential to improve outcome as they can solve anatomical hurdles for individual anatomical variation and focus on important procedures by reducing the level of fatigue of operating surgeons for lengthy and exhausting surgery. Funding Information: This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI18C2383). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The institutional review board for human investigations at Asan Medical Center approved this study with a waiver of informed consent from patients because of the use of retrospective clinical and imaging data. The data were de-identified, in accordance with the Health Insurance Portability and Accountability Act privacy rule.

BACKGROUND AND AIM OF THE STUDY Although dopamine and norepinephrine are recommended as first-line agents in the treatment of shock, it is unclear which is the optimal vasoactive inotropic agent (VIA) to manage postcardiotomy circulatory shock. This single-center, randomized clinical trial aimed to investigate the efficacy and safety of dopamine versus norepinephrine in postcardiotomy circulatory shock. METHODS We randomly assigned the patients with postcardiotomy circulatory shock to receive either dopamine or norepinephrine. When shock persisted despite the dose of 20 μg/kg/min of dopamine or the dose of 0.2 μg/kg/min of norepinephrine, epinephrine or vasopressin could be added. The primary endpoint was new-onset tachyarrhythmic event during drug infusion. Secondary endpoints included requirement of additional VIAs, postoperative complications, and all-cause mortality within 30 days of drug initiation. RESULTS At the planned interim analysis of 100 patients, the boundary for the benefit of norepinephrine has been crossed, and the study was stopped early. Excluding two patients withdrawing a consent, 48 patients were assigned to dopamine and 50 patients to norepinephrine. New-onset tachyarrhythmic event occurred in 12 (25%) patients in the dopamine and one (2%) patient in the norepinephrine group (p = .009). The requirement for additional VIAs was more common in the dopamine group (p

Background Paravalvular regurgitation (PVR) has been known to be the primary determinant of poor left ventricular (LV) mass regression after transcatheter aortic valve replacement (TAVR). However, the incidence of significant PVR has been reduced considerably as TAVR technology evolved rapidly. This study aimed to investigate the time course and impact of LV mass index (LVMi) regression on long-term clinical outcomes in severe aortic stenosis (AS) patients without significant PVR after TAVR. Methods Of 412 patients who underwent TAVR, 146 who had LV hypertrophy (LVMi ≥115 g/m2 for men and ≥ 95 g/m2 for women) at baseline and were alive at one year after TAVR were enrolled. The primary outcome was cardiovascular deaths and the impact of LVMi regression on clinical outcomes were examined. The patients with significant PVR were excluded. Results During a median follow-up of 40 months (interquartile range, 26–58 months), 9 (6.2%) cardiovascular deaths, 21 (14.4%) all-cause deaths, and 9 (6.2%) hospitalizations occurred. In the multivariable analysis, the percentage change of LVMi was an independent predictor of cardiovascular deaths (adjusted hazard ratio [HR], 1.03; 95% confidential interval [CI], 1.01–1.05; P = 0.010), and composite outcome of cardiovascular deaths and rehospitalization for heart failure (adjusted HR, 1.02; 95% CI, 1.00–1.04; P = 0.022). Baseline LVMi, eccentric hypertrophy, and TAVR-induced left bundle branch block were independently associated with LVMi regression. Conclusions In patients with severe AS who received successful TAVR without significant PVR, the degree of LVMi regression is an independent predictor of postoperative outcomes after TAVR.

Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Among the peroxins, PEX1 defects are the most common mutations in Zellweger syndrome. PEX1 is an AAA-ATPase that regulates the recycling of PEX5, which is essential for importing peroxisome matrix proteins. However, the post-transcriptional regulation of PEX1 is largely unknown. Here, we showed that heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) controls PEX1 expression. In addition, we found that depletion of HNRNPA1 induces autophagic degradation of peroxisome, which is blocked in ATG5-knockout cells. In addition, depletion of HNRNPA1 increased peroxisomal ROS levels. Inhibition of the generation of peroxisomal ROS by treatment with NAC significantly suppressed pexophagy in HNRNPA1-deficient cells. Taken together, our results suggest that depletion of HNRNPA1 increases peroxisomal ROS and pexophagy by downregulating PEX1 expression.

Background Patients presenting with descending aortic aneurysms developing after aortic dissection often undergo continued aortic expansion which may require operative interventions to address the risk of aortic rupture. In light of the current advances in various treatment options, including endovascular approaches, we analyzed our experience with open surgical repair (OSR) of aneurysms of the descending aorta following aortic dissection. Methods Patients who underwent open repair for aneurysmal changes of the descending aorta after chronic dissection were retrospectively studied. The 30-day operative mortality rate, midterm survival, and major complications were analyzed. Patients were divided into two categories; primary chronic type B aortic dissection and remnant repaired type A aortic dissection (RTAAD). Results There were 149 patients with enlargement of the descending thoracic aorta developing after aortic dissection. Of these, 49 patients had medical management, while the remaining 100 patients received OSR. These patients were included in the present analysis. The 30-day mortality and permanent paraplegia rates were 9% and 4%, respectively. The 1-, 3-, and 5-year survival rates were 83%, 80.9%, and 76.1%, respectively. The 1- and 5-year survival rates between the primary chronic type B aortic dissection and remnant RTAAD groups showed no significant between-group differences at 86.7% and 84.3%, and 80% and 71.3%, respectively (P = .289). The overall outcomes of other complications such as renal injury, bleeding reoperation, and extracorporeal membrane oxygenation support showed no significant between-group differences, including an insignificantly higher neurologic complication rate in the remnant RTAAD group. The survival rate in patients with Marfan syndrome was significantly higher than in the patients without Marfan syndrome (P = .033). Conclusions OSR for descending aortic aneurysms developing after chronic aortic dissection showed good early and mid- to long-term outcomes, with acceptably low complication rates. OSR for descending aortic aneurysm after chronic aortic dissection associated with Marfan syndrome also showed good early and mid- to long-term outcomes.

Various staffing models have been applied in intensive care units (ICUs) to improve outcomes. However, there is a lack of evidence regarding the effect of staffing models in cardiac surgery ICUs. Thus, we aimed to evaluate the efficacy of high-intensity staffing in cardiac surgery ICUs.From January 2013 to December 2016, 4676 adult patients were admitted to our cardiac surgery ICU after surgery. Excluding patients undergoing minor surgery or noncardiac-related surgery, 4038 patients were analyzed. Beginning in January 2015, patients were divided into low-intensity group (n = 1784) and high-intensity group (n = 2254) according to the study period. Primary outcomes were ICU and hospital length of stay, rates of transfusion and infection, and readmission to the ICU. Secondary outcomes were 30-day and ICU mortality. To reduce potential confounders, propensity score-matched analysis was performed.In the high-intensity group, ICU and hospital length of stay were significantly shorter (P .001). Incidence of readmission was lower in the high-intensity group (3.1% vs 12.5%; P .05). Infection rate in respiratory tract and bloodstream was lower in the high-intensity group (3.1% vs 5.0%; P .05). Transfusion rate and amount were also significantly lower in the high-intensity group (P .05). However, 30-day (1.9% vs 2.1%; P = .71) and ICU mortality (2.1% vs 2.7%; P = .31) were comparable between the groups.High-intensity staffing model during daytime hours by cardiac surgery intensivists significantly improved ICU-related outcomes. However, high-intensity staffing did not affect early mortality after cardiac surgery.

Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson's disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP

Background Various ECG criteria for left ventricular hypertrophy (LVH) have been proposed, but their association with clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement is unknown. We investigated the prevalence of ECG LVH according to different criteria and its prognostic impact on clinical outcomes after transcatheter aortic valve replacement. Methods and Results In this prospective observational cohort, we evaluated 700 patients who underwent transcatheter aortic valve replacement between March 2010 and December 2019. Baseline preprocedural LVH was defined by 3 ECG criteria—Sokolow‐Lyon, Romhilt‐Estes, and Cornell voltage criteria. The primary outcome was major adverse cardiac or cerebrovascular event (MACCE; composite of death, myocardial infarction, stroke, or rehospitalization from cardiovascular cause); the key secondary outcome was all‐cause and cardiovascular mortality. Among 596 eligible patients, the prevalence of LVH was determined as 56.3% by Sokolow‐Lyon, 31.1% by Romhilt‐Estes, and 48.1% by Cornell criteria. Regardless of the criteria, patients with ECG LVH had more severe aortic stenosis hemodynamics and higher left ventricular mass index. After multivariate adjustment, the presence of LVH by the Cornell criteria was significantly associated with lower risks of MACCE (adjusted hazard ratio [HR], 0.68; 95% CI, 0.51–0.91; P =0.009), all‐cause mortality (adjusted HR, 0.55; 95% CI, 0.34–0.90 [ P =0.017]), and cardiovascular mortality (adjusted HR, 0.40; 95% CI, 0.20–0.79 [ P =0.008]). However, this association was absent with the Sokolow‐Lyon and Romhilt‐Estes criteria. Conclusions ECG LVH by Cornell criteria only was significantly associated with lower risks of MACCE and all‐cause or cardiovascular mortality. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03298178.

ObjectiveThere is limited evidence regarding the effectiveness of left atrial appendage (LAA) closure during surgical ablation of atrial fibrillation (AF) in yielding superior clinical outcomes. This study aimed to evaluate the association of LAA closure versus preservation with the risk of adverse clinical outcomes among patients undergoing surgical ablation during cardiac surgery.MethodsWe evaluated 1640 patients (aged 58.8±11.5 years, 898 women) undergoing surgical ablation during cardiac surgery (including mitral valve (MV), n=1378; non-MV, n=262) between 2001 and 2018. Of these, 804 had LAA preserved, and the remaining 836 underwent LAA closure. Comparative risks of stroke and mortality between the two groups were evaluated after adjustments with inverse-probability-of-treatment weighting (IPTW). Longitudinal echocardiographic data (n=9674, 5.9/patient) on transmitral A-wave and E/A-wave ratio were analysed by random coefficient models.ResultsAdjustment with IPTW yielded patient cohorts well-balanced for baseline profiles. During a median follow-up of 43.5 months (IQR 19.0–87.3 months), stroke and death occurred in 87 and 249 patients, respectively. The adjusted risk of stroke (HR 0.85; 95% CI 0.52–1.39) and mortality (HR 0.80; 95% CI 0.61 to 1.05) did not differ significantly between the two groups. Echocardiographic data demonstrated higher transmitral A-wave velocity (group-year interaction, p=0.066) and lower E/A-wave ratio (group-year interaction, p=0.045) in the preservation group than in the closure group.ConclusionsLAA preservation during surgical AF ablation was not associated with an increased risk of stroke or mortality. Postoperative LA transport functions were more favourable with LAA preservation than with LAA closure.

Aortic valve calcium scoring by cardiac computed tomographic (CT) has been recommended as an alternative to classify the AS (aortic stenosis) severity, but it is unclear that whether CT findings would have additional value to discriminate significant AS subtypes including high gradient severe AS, classic low-flow, low gradient (LF-LG) AS, paradoxical LF-LG AS, and moderate AS. In this study, we examined the preoperative clinical and cardiac CT findings of different subtypes of AS in patients with surgical aortic valve replacement (AVR) and evaluated the subtype classification as a factor affecting post-surgical outcomes. This study included 511 (66.9 ± 8.8 years, 55% men) consecutive patients with severe AS who underwent surgical AVR. Aortic valve area (AVA) was obtained by echocardiography (AVAecho) and by CT (AVACT) using each modalities measurement of the left ventricular outflow tract. Patients with AS were classified as (1) high-gradient severe (n = 438), (2) classic LF-LG (n = 18), and (3) paradoxical LF-LG (n = 55) based on echocardiography. In all patients, 455 (89.0%) patients were categorized as severe AS according to the AVACT. However, 56 patients were re-classified as moderate AS (43 [9.8%] high-gradient severe AS, 5 [27.8%] classic LF-LG AS, and 8 [14.5%] paradoxical LF-LG AS) by AVACT. The classic LF-LG AS group presented larger AVACT and aortic annulus than those in high-gradient severe AS group and one third of them had AVACT ≥ 1.2 cm2. After multivariable adjustment, old age (hazard ratio [HR], 1.04, P = 0.049), high B-type natriuretic peptide (BNP) (HR, 1.005; P

The long-term prognostic impact of mildly decreased renal function in patients undergoing coronary revascularization is still unknown.The goal of this study was to investigate the long-term prognostic impact of mildly decreased renal function and comparative outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in such a risk group of patients.From the Asan Medical Center-Multivessel Revascularization registry, 10,354 eligible patients who underwent coronary revascularization were classified into 3 groups (stage I [n = 3,735]: normal renal function; stage II [n = 5,122]: mild dysfunction; and stage III [n = 1,497]: moderate dysfunction) according to estimated glomerular filtration rate. The primary outcome was the composite of death, spontaneous myocardial infarction, or stroke. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics.After propensity matching, the risk for primary composite outcome was not different between the stage I and the stage II group (HR: 1.12; 95% CI: 0.97-1.30). However, the risk of the primary outcome was significantly higher in the stage III group than in the stage I group (HR: 1.50; 95% CI: 1.22-1.84). The relative effect of PCI vs CABG for the primary outcome was similar in the matched cohort of each renal function group of stages I, II, and III.In patients with multivessel disease after revascularization by PCI or CABG, the presence of mildly decreased renal function was not significantly associated with an increased risk of the primary composite outcome and mortality. Comparative outcomes after PCI and CABG were similar in the borderline-risk group. (Asan Medical Center-Multivessel Revascularization registry; NCT02039752).

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

ObjectiveLittle information exists about inter-racial differences in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). We investigated whether differences in baseline characteristics between Asian and non-Asian population may contribute to disparities in clinical outcomes after TAVI.MethodsWe performed a registry-based, multinational cohort study of patients with severe AS who underwent TAVI at two centres in the USA and one centre in South Korea. The primary outcome was a composite of death, stroke or rehospitalisation at 1 year.ResultsOf 1412 patients, 581 patients were Asian and 831 were non-Asian (87.5% white, 1.7% black, 6.1% Hispanic or 4.7% others). There were substantial differences in baseline characteristics between two racial groups. The primary composite outcome was significantly lower in the Asian group than in the non-Asian group (26.0% vs 35.0%; HR 0.73; 95% CI 0.59 to 0.89; p=0.003). However, after adjustment of baseline covariates, the risk of primary composite outcome was not significantly different (HR 0.79; 95% CI 0.60 to 1.03; p=0.08). The all-cause mortality at 1 year was significantly lower in the Asian group than the non-Asian group (7.4% vs 12.5%; HR 0.60; 95% CI 0.41 to 0.88; p=0.009). After multivariable adjustment, the risk of all-cause mortality was also similar (HR 1.17; 95% CI 0.73 to 1.88; p=0.52).ConclusionsThere were significant differences in baseline and procedural factors among Asian and non-Asian patients who underwent TAVI. Observed inter-racial differences in clinical outcomes were largely explained by baseline differences in clinical, anatomical and procedural factors.Trial registration numberNCT03826264(https://wwwclinicaltrialsgov).

Because repairing visceral and segmental arteries in open surgical repair for thoracoabdominal aortic aneurysms is essential, two types of patient-specific graft reconstruction guides for reconstruction in the operating room have been developed that are applied clinically. However, designing the patient-specific guides is a time-consuming, laborious task. The aim of this study was to develop an automatic modeling method and to evaluate its accuracy.In 10 patients with thoracoabdominal aortic aneurysms, computer-aided designing was performed with conventional and automatic modeling methods for aortic reconstruction guides as follows: 1) a visualizing guide that presented the accurate shape of the aortic graft, visualizing the main aortic body and major blood vessels; and 2) a marking guide wherein the vessels in the visualizing guide were replaced by the protruding marking regions detectable by tactile sense. The script-based automatic guide modeling program was developed using an application programming interface presented in the 3-matic software with Python. For accuracy, the absolute mean differences of both modeling methods were assessed using Hausdorff distance. The modeling between conventional and automatic modeling methods was compared and evaluated using the Wilcoxon signed-rank test.The absolute mean difference between the conventional and automatic modeling methods were 6.05 ± 4.86 µm for the visualizing guide and 5.51 ± 4.85 µm for the marking guide. For the visualizing guide, the modeling time of the automatic modeling method was reduced by approximately more than thirtyfold than the conventional modeling method (p0.001). The marking guide was reduced about fortyfold (p0.001).Compared to the conventional method, the automatic modeling method was demonstrated to reduce the modeling time with reasonable accuracy, which could lead to a more efficient modeling and clinical application.

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

A mild-to-moderate aortic root aneurysm might be overlooked during the assessment of the donor heart. The use of the Z-score in such cases may be helpful in guiding clinical decision-making. To make a diagnosis of genetic aortopathy, a genetic panel study and matching with clinical criteria such as Ghent nosology are essential. Valve-sparing root reimplantation may be a viable option in cases with aortic root aneurysm developing after heart transplant.

Quality control of peroxisomes is essential for cellular homeostasis. However, the mechanism underlying pexophagy is largely unknown. In this study, we identified HSPA9 as a novel pexophagy regulator. Downregulation of HSPA9 increased macroautophagy/autophagy but decreased the number of peroxisomes in vitro and in vivo. The loss of peroxisomes by HSPA9 depletion was attenuated in SQSTM1-deficient cells. In HSPA9-deficient cells, the level of peroxisomal reactive oxygen species (ROS) increased, while inhibition of ROS blocked pexophagy in HeLa and SH-SY5Y cells. Importantly, reconstitution of HSPA9 mutants found in Parkinson disease failed to rescue the loss of peroxisomes, whereas reconstitution with wild type inhibited pexophagy in HSPA9-depleted cells. Knockdown of Hsc70-5 decreased peroxisomes in Drosophila, and the HSPA9 mutants failed to rescue the loss of peroxisomes in Hsc70-5-depleted flies. Taken together, our findings suggest that the loss of HSPA9 enhances peroxisomal degradation by pexophagy.

Current knowledge of the aortic root geometric anatomy and its surgical implications remain limited. We analyzed multiple predefined parameters of the aortic root to increase our understanding of the geometric changes that occur in normal and aneurysmal transformations. Between November 2003 and September 2015, the aortic roots of 107 healthy subjects (control group) and 105 annuloaortic ectasia (AAE) patients (AAE group) were analyzed using multiplanar reformatted computed tomographic images. The intercommissural distance (ICD), sinus width (SW), and sinus volume (SV) of the left (LCS), right (RCS), and noncoronary sinuses (NCS) of Valsalva were adopted as study parameters. In the control group, all study parameters of the LCS were smaller than those of the RCS and the NCS. In the AAE group, all parameters of the LCS were significantly smaller than those of the RCS or NCS, but the RCS and NCS parameters were similar. Proportionately less LCS enlargement relative to either the RCS or NCS was observed in root aneurysm(AAE group) than in the control group. We observed a distinct aortic root geometric pattern which was characterized by the LCS being smaller than either the RCS or NCS, while the latter were similar. This geometric configuration was significantly accentuated in AAE patients due to the greater disproportionate disparity in the LCS relative to either the RCS or NCS than in the roots of normal control subjects. Clin. Anat. 32:117-123, 2019. © 2019 Wiley Periodicals, Inc.

Mitochondria are essential for providing the energy necessary for neuronal function. Dysregulation of mitochondrial dynamics has been linked with the pathogenesis of many neurodegenerative diseases. Dynamin related protein 1 (Drp1) participates in fission activity in the mitochondria, and post-translational modifications to Drp1 modulate complex mitochondrial dynamics. However, the regulation of Drp1 at the post-transcriptional level remains poorly understood. In this study, we found that the RNA-binding protein Hu antigen R (HuR) post-transcriptionally regulates Drp1 expression. HuR interacts with Drp1 mRNA at its 3' untranslated region. Depletion of HuR reduces Drp1 expression, which leads to mitochondrial elongation in SH-SY5Y neuroblastoma cells. In contrast, ectopic expression of HuR enhances Drp1 expression, which promotes mitochondrial fragmentation in response to treatment with the mitochondrial complex 1 inhibitor MPP+. In addition, depletion of HuR suppressed the generation of mitochondrial ROS and cytotoxicity in MPP+ treated cells. Taken together, these findings suggest that HuR controls mitochondrial morphology via regulation of Drp1.

Background Surgical management of the mitral valve (MV) in patients with mild-to-moderate mitral dysfunction undergoing aortic valve replacement is still controversial. We investigated the echocardiographic data from patients with mild-to-moderate mitral dysfunction who did not undergo MV surgery. Materials and methods From January 1989 to June 2012, a total of 2731 patients underwent aortic valve replacement. Among these, 560 patients with mild-to-moderate mitral dysfunction were screened. Of these, 292 patients (61.9 ± 13.0 years; 113 females) who had not undergone MV surgery formed our study cohort. Survival, valve-related complication, and echocardiographic data were evaluated. Results There were three early deaths. During the mean follow-up period of 56.9 ± 46.5 months, there were 23 late deaths and 28 valve-related complications. Valve-related event-free survival at 5 years was 85.9% ± 2.4%. In serial postoperative echocardiographic evaluations (mean follow-up duration: 40.8 ± 44.5 months), 21 patients experienced a progression in late mitral dysfunction. At 5 years, 88.8% ± 2.7% of patients did not suffer from late mitral dysfunction. Based on multivariate analysis, rheumatic pathology of MV (Hazard Ratio: 3.88, 95% confidence intervals 1.60–9.39, p = 0.003) was an independent predictor of late mitral dysfunction. Conclusions Conservatively treated patients with mild-to-moderate mitral dysfunction exhibited acceptable clinical outcomes. Rheumatic pathology of MV is associated with a higher risk of progressive native MV dysfunction.

AimsTo evaluate the acute and long-term prognosis of acute aortic syndrome (AAS) according to the disease entity [intramural haematoma (IMH) vs. aortic dissection (AD)] and the anatomical location (type A vs. B).Methods and resultsA total of 1012 patients [672 with AD and 340 with IMH (33.6%)] were enrolled between 1993 and 2015. Compared with AD patients, IMH patients were older and had higher frequency of female sex and distal aorta involvement. The overall crude in-hospital mortality of AAS was 8.6%; type A AD [15.0%; adjusted hazard ratio (aHR) 30.4; 95% confidence interval (CI) 8.62–107.3; P < 0.001], type A IMH (8.0%; aHR 4.85; 95% CI 1.29–18.2; P = 0.019), type B AD (5.0%; aHR 3.51; 95% CI 1.00–12.4; P = 0.051), and type B IMH [1.5%; aHR 1.00 (reference)]. During a median follow-up duration of 8.5 years (interquartile range: 4.0–13.5 years), AD (aHR 2.78; 95% CI 1.87–4.14; P < 0.001) and type A (aHR 2.28; 95% CI 1.45–3.58; P < 0.001) was associated with a higher risk of aortic death. After 90 days, a risk of aortic death was no longer associated with anatomical location (aHR 0.74; 95% CI 0.40–1.36; P = 0.33), but remained associated with disease entity (aHR 1.83; 95% CI 1.10–3.04; P = 0.02).ConclusionThe clinical features, response to treatment strategy, and outcomes of IMH patients were distinct from those of AD patients. Both early and late survival was better for IMH than for AD. In addition to the anatomical location of AAS, the disease entity is an independent factor associated with both acute and long-term mortality in patients with AAS. Further investigation is necessary to confirm the prognostic implication of disease entity in different patient populations.

Background An optimal treatment for aortic regurgitation in Behcet’s disease has not been established. We investigated the effect of operative technique, prosthetic material, and immunomodulation therapy on surgical outcomes. Methods In this study, 23 patients with Behcet’s disease surgically treated for aortic regurgitation were assessed. Significant postoperative events were defined as death, aortic valve or graft-related problem(s), infective endocarditis, disabling stroke, and aortic valve or root reoperation. Surgical procedures were classified as isolated aortic valve replacement, bioprosthetic root replacement, and mechanical root replacement. Allograft root replacements were included in the bioprosthetic root replacement group. Results A total of 40 operations, including 39 aortic valve or root surgeries and 1 orthotopic heart transplantation, were performed on patients confirmed with Behcet’s disease. However, the study only reviewed 35 of the 40 cases (4 cases with inadequately documented medical records and 1 heart transplantation case were excluded). Significant adverse events occurred in 8 of 11 (73%) isolated aortic valve replacement, 9 of 12 (75%) bioprosthetic root replacement (5 xenografts and 7 allografts), and 4 of 12 (33%) mechanical root replacement cases. Multivariate analysis revealed that the 1-month postdischarge C-reactive protein level and operative age were independent predictive factors for postoperative event-free survival. Mechanical root replacement was identified as the most significant predictive factor leading to positive outcomes (hazard ratio, 0.147; 95% confidence interval, 0.028 to 0.766; p = 0.023). Conclusions The findings suggest that mechanical root replacement combined with a low postoperative C-reactive protein level maintained through adjunctive immunomodulation therapy may lead to optimal surgical outcomes in Behcet’s disease associated with severe aortic regurgitation.

Aortic valve (AV) replacement (AVR) is the only effective treatment for severe aortic stenosis (AS). However, survival benefits by performing AVR in asymptomatic AS patients with preserved left ventricular (LV) function remains controversial. This study included 468 patients (aged 64.2 ± 13.0 years, 232 women) with preserved LV function (≥50%) and severe AS (AV area ≤1.0 cm2, peak trans-AV velocity [Vmax] ≥4.0 m/s, or mean AV pressure gradient ≥40 mm Hg) between 2000 and 2015. AVR was performed in 221 (47.2%) patients early (within 3 months; n = 130, 27.8%) or during follow-up (n = 91, 19.4%), whereas the remainder (n = 247) received medical treatment. Time-dependent Cox regression analyses were performed to determine the impact of AVR on long-term survival outcomes. During a median follow-up of 60.9 months (quartile 1 to 3, 29.9 to 107.0 months), 72 (15.4%) patients developed AS-related symptoms and 146 (31.2%) died. On time-dependent Cox models, AVR was associated with a significant risk reduction in all-cause death (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40 to 0.97; p = 0.036) and cardiac death (HR, 0.59; 95% CI, 0.35 to 0.995; p = 0.048) after adjusting for significant contributors to mortality. Survival benefits by performing AVR were manifested in most risk subgroups. In conclusion, AVR in asymptomatic severe AS patients with preserved LV function resulted in significant survival benefits, suggesting that early recruitment for AVR may be warranted before ventricular dysfunction or symptom development.

Several studies have shown that dysfunction of macroautophagy/autophagy is associated with many human diseases, including neurodegenerative disease and cancer. To explore the molecular mechanisms of autophagy, we performed a cell-based functional screening with SH-SY5Y cells stably expressing GFP-LC3, using an siRNA library and identified TMED10 (transmembrane p24 trafficking protein 10), previously known as the γ-secretase-modulating protein, as a novel regulator of autophagy. Further investigations revealed that depletion of TMED10 induced the activation of autophagy. Interestingly, protein-protein interaction assays showed that TMED10 directly binds to ATG4B (autophagy related gene 4B cysteine peptidase), and the interaction is diminished under autophagy activation conditions such as rapamycin treatment and serum deprivation. In addition, inhibition of TMED10 significantly enhanced the proteolytic activity of ATG4B for LC3 cleavage. Importantly, the expression of TMED10 in AD (Alzheimer disease) patients was considerably decreased, and downregulation of TMED10 increased amyloid-β (Aβ) production. Treatment with Aβ increased ATG4B proteolytic activity as well as dissociation of TMED10 and ATG4B. Taken together, our results suggest that the AD-associated protein TMED10 negatively regulates autophagy by inhibiting ATG4B activity.Abbreviations: Aβ: amyloid-β; AD: Alzheimer disease; ATG: autophagy related; BECN1: beclin 1; BiFC: bimolecular fluorescence complementation; CD: cytosolic domain; GFP: green fluorescent protein; GLUC: Gaussia luciferase; IP: immunoprecipitation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LD: luminal domain; PD: Parkinson disease; ROS: reactive oxygen species; siRNA: small interfering RNA; SNP: single-nucleotide polymorphisms; TD: transmembrane domain; TMED10: transmembrane p24 trafficking protein 10; VC: C terminus of Venus fluorescent protein; VN: N terminus of Venus fluorescent protein.

Background Data on robotic-assisted surgical atrial fibrillation (AF) ablation in patients undergoing mitral valve (MV) operations are lacking. This study aimed to evaluate early and late outcomes after robotic-assisted ablation of AF combined with MV surgery. Methods Between 2007 and 2017, this study enrolled 94 patients (age: 53.9 ± 12.7 years; 67 men) undergoing AF ablation by using an argon-based flexible cryoablation system during robotic-assisted MV surgical procedures. Persistent (n = 34, 36.2%) or long-standing persistent (n = 38, 40.4%) AF was present in most patients. Primary valve procedures included isolated mitral repair in 58 patients, isolate mitral replacement in 2 patients, and combined mitral and tricuspid repair in 34 patients. Results Sixty patients (63.8%) received left-side-only AF ablation, whereas the others (n = 34, 36.2%) received biatrial ablation. The operation times for cardiopulmonary bypass and aortic cross-clamping were 222.7 ± 57.8 minutes and 134.1 ± 30.4 minutes, respectively. No early death was seen. Major early complications included neurologic injury in 2 patients (2.1%) and low cardiac output syndrome in 2 patients (2.1%). No patients required permanent pacemaker implantation. Early AF occurred in 14 patients (14.9%) during a postablation blanking period (90 days). During a median follow-up of 49.6 months (quartiles 1 to 3: 17.2 to 79.4 months, 95.7% complete), there were two late deaths (0.49% per patient-year) and one stroke (0.25% per patient-year). Five-year survival was greater than 96%, and results from largely electrocardiograms showed a low recurrence of AF (2.2% at 1 year, 6.7% at 5 years). Conclusions Surgical AF ablation with the use of robotic-assistance in the setting of mitral valve surgery showed excellent safety and favorable long-term clinical outcomes.

Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.

Evaluation of left ventricular global longitudinal strain (LVGLS) has allowed better characterization than left ventricular ejection fraction (LVEF) of subtle differences in left ventricular performance. The aim of this study was to determine whether LVGLS has prognostic value in patients with severe aortic stenosis and preserved LVEF undergoing transcatheter aortic valve implantation (TAVI).Among 412 consecutive patients who underwent TAVI, 344 patients (mean age, 78.9 ± 5.0 years; 161 men) with preserved LVEF (≥50%) at baseline were analyzed. Patients with low LVEF (50%) were used as a comparison group in the survival analysis. The primary and secondary end points were all-cause death and a composite of cardiovascular death and heart failure hospitalization, respectively.The mean LVGLS and LVEF were -17.1 ± 2.7% and 63 ± 5%, respectively. Impaired LVGLS was defined as -16%, which was the first LVGLS quartile (cutoff value, -16%). The estimated actuarial 5-year survival rate was 81.7 ± 4.2% in the normal LVGLS group and 66.8 ± 7.5% in the impaired LVGLS group (P = .005). In the multivariable analysis, impaired LVGLS was an independent predictor of all-cause death (adjusted hazard ratio, 2.26; 95% CI, 1.11-4.60) and the composite outcome (adjusted hazard ratio, 3.03; 95% CI, 1.45-6.33). Moreover, the impaired LVGLS group had a poor prognosis, similar to the impaired LVEF group (50%). The addition of the absolute value of LVGLS to the clinical parameters and LVEF led to significant improvement in the prediction of all-cause mortality.In patients with severe aortic stenosis and preserved LVEF undergoing TAVI, subclinical LV dysfunction defined by impaired LVGLS is independently associated with poor clinical outcomes. LVGLS measurement provides incremental prognostic value above the established clinical and echocardiographic parameters.

More evidence is required with respect to the comparative effectiveness of percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DESs) versus coronary artery bypass grafting (CABG) in contemporary clinical practice. This prospective observational registry–based study compared the outcomes of 6,647 patients with multivessel disease who underwent PCI with second-generation DES (n = 3,858) or CABG (n = 2,789) between January 2006 and June 2018 and for whom follow-up data were available for at least 2 to 13 years (median 4.8). The primary outcome was a composite of death, spontaneous myocardial infarction, or stroke. Baseline differences were adjusted using propensity scores and inverse probability weighting. In the overall cohort, there were no significant between-group differences in the adjusted risks for the primary composite outcome (hazard ratio [HR] for PCI vs CABG 1.03, 95% confidence interval [CI] 0.86 to 1.25, p = 0.73) and all-cause mortality (HR 0.95, 95% CI 0.76 to 1.20, p = 0.68). This relative treatment effect on the primary outcome was similar in patients with diabetes (HR 1.15, 95% CI 0.91 to 1.46, p = 0.25) and without diabetes (HR 0.95, 95% CI 0.73 to 1.22, p = 0.67) (p for interaction = 0.24). The adjusted risk of the primary outcome was significantly greater after PCI than after CABG in patients with left main involvement (HR 1.39, 95% CI 1.01 to 1.90, p = 0.044), but not in those without left main involvement (HR 0.94, 95% CI 0.76 to 1.16, p = 0.56) (p = 0.03 for interaction). In this prospective real-world long-term registry, we observed that the risk for the primary composite of death, spontaneous myocardial infarction, or stroke was similar between PCI with contemporary DES and CABG.

Aims This study aimed to assess the impact of valvular/subvalvular calcium burden on procedural and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Methods and results In this prospective observational cohort study, we included patients with AS undergoing TAVR between March 2010 and December 2019. Calcium burden at baseline was quantified using multidetector computed tomography and the patients were classified into tertile groups according to the amount of calcium. Procedural outcomes [paravalvular leakage (PVL) or permanent pacemaker insertion (PPI)] and 12-month clinical outcomes (composite of death, stroke, or rehospitalization, and all-cause mortality) were assessed. A total of 676 patients (age, 79.8 ± 5.4 years) were analysed. The 30-day rates of moderate or severe PVL (P-for-trend = 0.03) and PPI (P-for-trend = 0.002) proportionally increased with the tertile levels of calcium volume. The 12-month rate of primary composite outcomes was 34.2% in low-tertile, 23.9% in middle-tertile, and 25.8% in high-tertile groups (log-rank P = 0.02). After multivariable adjustment, the risk for primary composite outcomes at 12 months was not significantly different between the tertile groups of calcium volume [reference = low-tertile; middle-tertile, hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.54–1.22; P = 0.31; high-tertile, HR 0.93; 95% CI 0.56–1.57; P = 0.80]. A similar pattern was observed for all-cause mortality. Conclusion The rates of PVL and PPI proportionally increased according to the levels of valvular/subvalvular calcium volume, while the adjusted risks for composite outcomes and mortality at 12 months were not significantly different.

The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based screening system was used to identify novel lysophagy modulators. Triamterene (6-phenylpteridine-2,4,7-triamine) was identified as one of the most potent lysophagy inducers from the screening process. We found that triamterene causes lysosomal rupture without affecting other cellular organelles and increases autophagy flux in HepG2 cells. Damaged lysosomes in triamterene-treated cells were removed by autophagy-mediated pathway, which was inhibited by depletion of the autophagy regulator, ATG5 or SQSTM1. In addition, treatment of triamterene decreased the integrity of lysosome and cell viability, which were rescued by removing the triamterene treatment in HepG2 cells. Hence, our data suggest that triamterene is a novel lysophagy inducer through the disruption of lysosomal integrity. Supplementary Information The online version contains supplementary material available at 10.1007/s12272-021-01335-5.

Reconstruction of the visceral and segmental arteries is a challenging part of open surgical repair of extensive thoracoabdominal aortic aneurysm (TAAA). For more efficient reconstruction of these branching vessels, a technique of using pre-hand-sewn multi-branched aortic graft (octopod technique) has been adopted with the aid of 3D-printing-guidance in latest cases. The octopod graft has been employed for the extent II or III TAAA repair, in which the commercially available two 4-branched aortic grafts were interconnected before surgery. Since January 2017, 3D-printed-aortic model has been used to efficiently replicate the projected aorta shape fitted to patient's anatomy. From May 2015 through Oct 2019, 20 patients (median age, 40years; range, 23-65; 5 females) underwent extent II or III TAAA repair using the octopod technique with (n = 9) or without (n=11) 3D-printing-guidance. Thirteen patients (65%) were diagnosed as Marfan syndrome. Eighteen patients (90%) had undergone prior aorta repair including 4 patients (20%) undergoing redo-thoracotomy. Revascularization of segmental arteries was conducted in 19 patients (95%, median, N = 2; range, 1-4). Median pump and entire procedural times were 173.5 minutes (interquartile range [IQR], 136.8-187.8) and 441 minutes (IQR, 392.8-492.3), respectively. There was no operative mortality or stroke, however, permanent paraplegia occurred in one patient (5%). During follow-up (median 35months, range 1-56 months), all of reconstructed branched vessels remained wide patent on CT. The octopod technique for open TAAA repair showed favorable early and mid-term results with high feasibility of procedural efficiency. 3D-printing guidance is expected to improve the flow of surgical procedures especially in challenging anatomy.

Immediate improvement in left ventricular ejection fraction (LVEF) following transcatheter aortic valve implantation (TAVI) is common; however, data on the pattern and prognostic value of this improvement are limited. To evaluate the incidence, predictors, and clinical impact of immediate improvement in LVEF, we studied 694 consecutive patient who had underwent successful TAVI for severe aortic stenosis (AS) between March 2010 and December 2019. We defined immediate improvement of LVEF as an absolute increase of ≥5% in LVEF at post-procedure echocardiogram. The primary outcome was major adverse cardiac or cerebrovascular event (MACCE), defined as a composite of death from cardiovascular cause, myocardial infarction, stroke, or rehospitalization from cardiovascular cause. Among them, 160 patients showed immediate improvement in LVEF. The independent predictors of immediate LVEF improvement were absence of hypertension and baseline significant aortic regurgitation, and greater baseline LV mass index. Immediate improvement in LVEF was significantly associated with a lower risk of MACCE (adjusted hazard ratio, 0.48; 95% confidence interval, 0.28–0.81; p = 0.01). In conclusion, approximately one-fourth of patients with severe AS who underwent TAVI showed immediate improvement in LVEF during index hospitalization. Immediate LVEF recovery was associated with a lower risk of MACCE during follow-up.

Background We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. Methods From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. Results Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR group = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). Conclusion Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group., Graphical Abstract

We report a case of recurrent left atrial (LA) intimal sarcoma invading pulmonary veins (PV) which was treated by a novel surgical approach—resecting LA wall and PVs down to segmental levels, and then creating neo-LA using lung hilum and posterior mediastinal soft tissue without further reconstructive procedures. This surgical approach may be useful in selected cases with primary cardiac malignancy involving LA and PVs in the aim of achieving complete resection of the tumor. Left heart sarcoma is an extremely uncommon but lethal disease which poses challenges to physicians due to its equivocal presentation, limited treatment option and dismal prognosis. Although the mainstay of treatment is a complete resection, it is technically demanding due to a lack of extensive experience in cardiac malignancy surgery and its very location or involvement in vital structures. Therefore, establishing a creative surgical strategy to overcome aforementioned obstacles and to achieve complete resection with tumor-free resection margin is needed. Here in, we report a case of recurrent left atrial sarcoma which was removed by noteworthy surgical technique.

Background Sarcopenia, known as physical frailty, is highly prevalent in older patients and is related to adverse outcomes post-cardiac surgery. However, whether sarcopenia assessment can reclassify an individual patients’ risk, which is estimated by Society of Thoracic Surgeons-predicted risk of mortality scores in patients who undergo surgical aortic valve replacement, is unclear. Methods This retrospective, single center, cohort study comprised 874 patients aged ≥65 years who underwent surgical aortic valve replacement between 2009 and 2016. Total skeletal muscle area was calculated using height-squared and was measured by preoperative computed tomography at the third lumbar vertebra inferior border using machine learning-based analysis. Sex-specific Z-scores were calculated and patients in the lowest Z-score tertile were considered to have sarcopenia. The primary endpoint was 30-day mortality, and secondary endpoints were in-hospital events, 1-year mortality, and long-term mortality. Results Thirty-day mortality, 30-day in-hospital events, and one-year mortality rates were 4.7%, 17.6%, and 8.0%, respectively. As the Z-score decreased, early adverse event odds showed a stepwise increase. Sarcopenia were independently associated with higher 30-day mortality, 30-day in-hospital events, and 1-year mortality. Reclassification analyses showed improvements in the ability to predict early adverse events after adding the Z-scores over and above the Society of Thoracic Surgeons-predicted risk of mortality scores (All, p Conclusions Sarcopenic patients had significantly higher risks of early adverse events and long-term mortality after undergoing surgical aortic valve replacement than non-sarcopenic patients. Sarcopenia determined by preoperative computed tomography can enhance the prediction of postoperative outcome risk.

OBJECTIVES With the goal of evaluating the impact of experiences at our centre on comparative outcomes between total arch and hemiarch repairs, we reviewed our 21 years of experience with operations for acute type I aortic dissection. METHODS Between 1999 and 2019, a total of 365 patients (177 women; 56.8 ± 12.9 years) with acute type I aortic dissection who had a hemiarch (n = 248) or a total arch replacement (n = 117) were evaluated, and the trends in comparative outcomes were analysed. RESULTS Over time, deep hypothermic circulatory arrest and retrograde cerebral perfusion were replaced by moderate hypothermia and antegrade cerebral perfusion with the introduction of dedicated aortic surgeons. Overall, operative deaths decreased from 11.0% in time quartile 1 to 2.2% in time quartile 4 (P = 0.090). After adjustment with the use of inverse probability weighting, the total arch group compared with the hemiarch group was at a similar risk of mortality [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.22–2.43; P = 0.71] but at a greater risk of neurological deficit (OR 3.28, 95% CI 1.23–8.98; P = 0.017) in the earlier half period (1999–2009). In the later period (2009–2019), however, both the risks of mortality (OR 0.32, 95% CI 0.03–1.59; P = 0.23) and of neurological injuries (OR 0.42, 95% CI 0.12–1.18; P = 0.13) were comparable between the 2 groups (P for interaction in terms of neurological deficit = 0.007). The multivariable logistic regression model revealed that dedicated aortic surgeons independently contributed to decreased risk of death (OR 0.30, 95% CI 0.09–0.84; P = 0.036). CONCLUSIONS These findings indicate that accumulating institutional experiences, along with resultant improvements in surgical strategies and outcomes, may neutralize the surgical risk gap between total arch and hemiarch repair in acute type I aortic dissection.

There is limited data regarding the association between sarcopenia and clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI). From the prospective ASAN-TAVI registry, we evaluated a total of 522 patients with severe aortic stenosis who underwent TAVI between March 2010 and November 2018. Routine pre-TAVI computed tomography scan was used to calculate the skeletal muscle index (SMI), which was defined as skeletal muscle area at the L3 level divided by height squared; subject patients were classified into the gender-specific tertile groups of SMI. The patients' mean age was 79 years and 49% were men. Mean SMI values were 41.3 ± 6.7 cm2/m2 in men and 34.1 ± 6.5 cm2/m2 in women. The Kaplan-Meier estimates of all-cause mortality at 12 months were higher in the low-tertile group than in the mid- and high-tertile groups (15.5%, 7.1%, and 6.2%, respectively; p = 0.036). In multivariate analysis, low-tertile of SMI was an independent predictor of mortality (vs high-tertile of SMI, hazard ratio 2.69; 95% confidence interval, 1.18 to 6.12; p = 0.019). The all-cause mortality was substantially higher in the groups with high-surgical risk plus low SMI tertile. The risk assessment with addition of SMI on conventional STS-PROM score was significantly improved by statistical measures of model reclassification and discrimination. In patients who underwent TAVI, sarcopenia measured by SMI was significantly associated with an increased risk of 1-year mortality. The prognostic impact of SMI-measured sarcopenia was more prominent in patients with high surgical risks.

Background We aimed to evaluate the effect of limited volume of hydroxyethyl starch (HES) administration on postoperative renal function in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Methods One thousand six hundred fifty-seven patients undergoing cardiac surgery under CPB over two years were included. The patients were divided according to the amount of HES administrated during the first 2 days post-surgery; moderate dose HES (≥20 ml/kg) versus low dose HES ( Results Incidence of acute kidney injury (AKI) was higher in the moderate HES group (p = .02). However, new renal replacement therapy (RRT) (P = .30) and early mortality (p = .97) was similar between the groups. When adjusted, the moderate HES use was associated with AKI (OR, 1.66; 95% CI, 1.12–2.44; p = .01), but did not increase the risk of new RRT (OR, 1.27; 95% CI, 0.71–2.18; p = .40) or early mortality (HR, 0.73; 95% CI, 0.29–1.81; p = .50). Conclusions The moderate dose administration of HES (≥20 ml/kg) in the postoperative period following cardiac surgery might be associated with the risk of AKI. However, it was not associated with serious adverse outcomes such as new RRT or mortality. Further randomized controlled studies are needed to validate study results.

ObjectivesAlthough the incidence of patients with isolated tricuspid regurgitation (TR) is increasing, data regarding the clinical outcomes of isolated TR surgery are limited. This study sought to investigate the prognostic implications according to procedural types, and to identify preoperative predictors of clinical outcomes after isolated TR surgery.MethodsAmong consecutive 2610 patients receiving tricuspid valve (TV) procedure, we analysed 238 patients (age, 59.6 years; 143 females) who underwent stand-alone TV surgery (repair, 132; replacement, 106) for severe TR. Primary outcome was the composite of all-cause mortality and heart transplantation. Clinical outcomes between the repair and the replacement groups were compared after adjusting with the inverse probability of treatment weighting (IPTW) method.ResultsDuring follow-up (median, 4.1 years), 53 patients died and 4 received heart transplantation. Multivariable analysis revealed that age (p=0.001), haemoglobin level (p=0.003), total bilirubin (p=0.040), TR jet area (p=0.005) and right atrial (RA) pressure (p=0.022) were independent predictors of the primary outcome. After IPTW adjustment, there were no significant intergroup differences in the risk of primary outcome (HR 1.01; 95% CI 0.55 to 1.87). In the subgroup analysis, tricuspid annular diameter was identified as a significant effect modifier (p=0.012) in the comparison between repair versus replacement, showing a trend favouring replacement in patients with annular diameter >44 mm.ConclusionsThe outcomes of stand-alone severe TR surgery were independently associated with the severity of TR and RA pressure. In selected patients with severe annular dilation >44 mm, replacement may become a feasible option.

Obesity and overweight have been associated with better clinical outcomes in different populations with a diverse spectrum of cardiovascular disease (obesity paradox). However, conflicting data exist about the relation between body mass index (BMI) and outcomes after transcatheter aortic valve implantation (TAVI). The aim of this study is to evaluate the association of body mass index with clinical outcomes in patients with severe aortic stenosis (AS) who underwent TAVI. The study cohort included 379 consecutive patients with symptomatic severe AS who underwent TAVI between March 2010 and February 2017 in 3 centers in East Asia. Patients were grouped into tertiles of baseline BMI (first tertile: ≤22.3 kg/m2, second tertile: 22.4 to 24.8 kg/m2, and third tertile: ≥24.9 kg/m2). The primary outcome was a composite of death from any causes or stroke at 1 year. The median (interquartile range) BMI was 23.5 (21.8 to 26.1) kg/m2. During the median follow-up of 18.4 months, there were 69 deaths and 23 strokes. At 1 year, the primary outcome occurred in 21.9% in the first tertile, 18.7% in the second tertile, and 7.8% in the third tertile, respectively (p = 0.009). After adjustment for confounding variables, an inverse relation was observed between BMI and primary outcome: with the third BMI tertile as the reference category, the adjusted hazard ratios were 2.51 (95% confidence interval, 1.20 to 5.26) for the second BMI tertile and 2.61 (95% confidence interval, 1.20 to 5.66) for the first BMI tertile. In conclusion, in patients with severe AS who underwent TAVI, an inverse association between BMI and the risk of death or stroke was observed.