Safety Time and Optimal Temperature of Unilateral Antegrade Cerebral Perfusion in Acute Type A Aortic Dissection: A Single-Center 15-Year Experience.

Background: The optimal level of hypothermia and safe time of unilateral antegrade cerebral perfusion (uACP) in acute type A aortic dissection (ATAAD) repair remain controversial. Objectives: To analyze the association of uACP time and circulatory arrest temperature with surgical outcomes of ATAAD. Methods: We retrospectively analyzed 263 patients who had undergone ATAAD repair between 2006 and 2020 using uACP. The patients were stratified by three chronologically equivalent periods (period 1, 2006 to 2010; period 2, 2011 to 2015; period 3, 2016 to 2020) to demonstrate the decade-long evolution of surgical strategy and outcomes. Results: The mean age of the patients was 59.4 ± 12.5 years, and 68.8% were male. The hospital mortality rates were 15.1%, 12.9%, and 11.0% from period 1 to 3 (p = 0.740). The median circulatory arrest temperatures were 20, 23, and 25 °C (p < 0.001), respectively, and the median uACP times were 72, 59, and 41 minutes (p < 0.001). The incidence rates of postoperative permanent neurologic deficits were 13.2%, 10.9%, and 18.3% (p = 0.312), and those of transient neurologic deficits were 9.4%, 10.9%, and 11.9% (p = 0.936), respectively. Multivariate logistic regression analysis showed that uACP time ≥ 60 minutes was an independent predictor of hospital mortality rather than postoperative stroke. ROC curve analysis estimated an optimal cutoff value of 52 minutes of uACP time when the circulatory arrest temperature was ≥ 25 °C to predict hospital mortality (area under the curve: 0.72). Conclusions: Unilateral antegrade cerebral perfusion time was associated with hospital mortality after ATAAD surgery. A safe threshold of 50 to 60 minutes of uACP should be considered.

Post-Coronary Artery Bypass Medications in Dialysis Patients: Do We Need to Change Strategies?

BACKGROUND: Coronary artery bypass grafting (CABG) is frequently performed in patients with end-stage renal disease (ESRD) together with severe coronary artery disease, after which, patients with ESRD have higher surgical risk and poorer long-term outcomes. We report our experience in patients with ESRD who survived in CABG and identify predictors of long-term outcomes. METHODS: We retrospectively investigated 93 consecutive patients with ESRD who survived to discharge after isolated CABG between January 2005 and December 2016 at our institution. Long-term outcomes, including all-cause mortality after discharge, readmission due to major adverse cardiac events, and reintervention, were evaluated. Predictors affecting long-term outcomes were also analyzed. RESULTS: The rates of freedom from all-cause mortality after discharge in 1, 3, 5, and 10 years were 92.1, 81.3, 71.9, and 34.9%, respectively. The rates of freedom from readmission due to major adverse cardiac events in 1, 3, 5, and 10 years were 90.7, 79.1, 69.9, and 55.6%, respectively. The rates of freedom from reintervention in 1, 3, 5, and 10 years were 95.3, 86.5, 79.0, and 66.6%, respectively. Postoperative ß-blocker and statin use significantly improved overall long-term survival (ß-blocker, p = 0.013; statin, p = 0.009). After case-control matching, patients who received statins showed better long-term survival than those without statins. The comparison of long-term survival between patients with and without ß-blockers showed no significant difference after matching. CONCLUSIONS: After CABG, dialysis patients who survived to discharge had acceptable long-term overall survival. Post-CABG statin use in dialysis patients is a predictor of better long-term survival.

Circulating cells contribute to cardiomyocyte regeneration after injury.

RATIONALE: The contribution of bone marrow-borne hematopoietic cells to the ischemic myocardium has been documented. However, a pivotal study reported no evidence of myocardial regeneration from hematopoietic-derived cells. The study did not take into account the possible effect of early injury-induced signaling as the test mice were parabiotically paired to partners immediately after surgery-induced myocardial injury when cross-circulation has not yet developed. OBJECTIVE: To re-evaluate the role of circulating cells in the injured myocardium. METHODS AND RESULTS: By combining pulse-chase labeling and parabiosis model, we show that circulating cells derived from the parabiont expressed cardiac-specific markers in the injured myocardium. Genetic fate mapping also revealed that circulating hematopoietic cells acquired cardiac cell fate by means of cell fusion and transdifferentiation. CONCLUSIONS: These results suggest that circulating cells participate in cardiomyocyte regeneration in a mouse model of parabiosis when the circulatory system is fully developed before surgery-induced heart injury.

Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing.

BACKGROUND: Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. MATERIALS AND METHODS: Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0.5 µg/kg/d, i.p.) for 2 wk. The final-to-initial wound area ratio was measured for 14 d. Levels of superoxide anions and proinflammatory cytokines in the wound were determined. Angiogenesis was assessed using the Matrigel assay. Expression levels of proangiogenic factors and extracellular matrix proteins were measured. RESULTS: Ex4 restored wound closure in diabetic rats and significantly suppressed the generation of superoxide anions and interleukin-6 in wounds. The number of circulating endothelial progenitor (CD34+/KDR+) cells increased significantly in Ex4-treated diabetic rats, which also showed increased capillary tube formation. Protein levels of vascular endothelial growth factor receptor-2, phosphorylated endothelial nitric oxide synthase, matrix metalloproteinase-2, and transforming growth factor-ß were increased in diabetic rats receiving Ex4 therapy. Ex4-enhanced vascularity, dermal regeneration, and epidermal regeneration, while it decreased hemorrhaging and increased the number of proliferative cells in the dermis. CONCLUSIONS: Ex4 accelerated excisional wound healing in subjects with diabetes. Glp-1R activation attenuates inflammatory response and enhances angiogenesis during the early proliferation phase of wound healing in diabetic subjects, while it enhances transforming growth factor-ß/matrix metalloproteinase-mediated regeneration during the maturation phase. These results suggest that Ex4 could be used as a standard hypoglycemic agent in diabetic patients with wound injury.

High-dose calcineurin inhibitor-free everolimus as a maintenance regimen for heart transplantation may be a risk factor for Pneumocystis pneumonia.

BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients. METHODS: We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal impairment, or a history of malignancy-were switched from tacrolimus to everolimus. The Control group consisted of 19 patients who remained on the standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The primary outcome was survival, and the secondary outcomes were bacterial, viral, fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and rejection (≥2R). RESULTS: During a 53.3±25.6-month follow-up, the survival rate, rejection rate, and number of infections, except for PJP, were not significantly different between the two groups. In the Study group, 6 patients were diagnosed with PJP 33±18.2 months after switching. None of the Control group patients were diagnosed with PJP during follow-up. CONCLUSIONS: A high-dose CNI-free everolimus maintenance regimen might yield a higher incidence of post-transplantation PJP.

Role of Left Atrial Reservoir Strain Rate in Left Atrial Remodeling in Severe Mitral Regurgitation.

BACKGROUND: Impaired left atrial (LA) reservoir deformation has been found to be associated with poor functional capacity and outcomes in severe chronic mitral regurgitation (MR). Among patients with primary MR (valve incompetence due to mitral valve pathology), we focus on Carpentier II classification (prolapse or flail mitral valve) and aim to investigate determinants for decreased LA reservoir deformation and its impact on LA remodeling in severe MR. METHODS: Among 159 consecutive patients with severe chronic Carpentier II MR (left ventricular ejection fraction ≥ 60%), 55 underwent follow-up echocardiography, which was compared with their baseline study. We used the change of LA volume index as the rapidity of LA remodeling, LA eccentricity index as LA sphericity, and peak LA reservoir strain as well as reservoir strain rate (LASRR) derived from two-dimensional speckle-tracking echocardiography as LA reservoir function. RESULTS: Older age, elongated left atrium, increased LA volume index, as well as reduced left ventricular global longitudinal strain and LA ejection fraction all linked to a poor baseline LASRR (all p < 0.001). A second echocardiography during a mean follow-up of 15.3 ± 8.3 months revealed an enlarged left atrium (increased interval change of LA volume index; p < 0.001). In multivariate analysis, only the difference between the baseline and follow-up LASRR values (Δ: LASRR; odds ratio (OR) 0.037, 95% confidence interval (CI) 0.003-0.496, p = 0.013) predicted accelerated LA remodeling. A poor baseline LASRR was significantly associated with its profound deterioration during the follow-up period (ß: = -0.424, p = 0.002). CONCLUSION: In severe chronic Carpentier II MR, a reduced follow-up LASRR predicted future accelerated LA remodeling. Patients with a poor baseline LASRR are at a higher risk of its deterioration.

Right Ventricular Pacing-Induced Heart Failure after Mitral Valve Replacement.

UNLABELLED: It is an unfortunate fact that pacing-induced heart failure after cardiac surgery is frequently ignored by medical professionals. A 60-year-old woman with chronic atrial fibrillation with a single-lead right ventricular permanent pacemaker for a prolonged ventricular pause underwent mitral valve replacement 6 months later for severe stenosis (NYHA functional class III). The patient's pacing rate was increased from the preoperative level of 60 beats per minute (bpm) to 70 bpm in order to facilitate weaning from the cardiopulmonary bypass. However, her postoperative low cardiac output continued to progress, despite the presence of inotropes. The patient's cold limbs and oliguria persisted until she underwent echocardiographic imaging, which showed dyssynchronous ventricular contraction 29 days post-surgery but which improved after the pacing rate was reduced below her spontaneous rate. Ultimately, clinicians should exercise caution when increasing right ventricular pacing for postoperative stunned myocardium. Due to the problems that can arise from an increased pacing rate, postoperative pacing strategy in patients complicated with low cardiac output after mitral valve replacement merits further discussion. KEY WORDS: Dyssynchrony; Mitral valve replacement; Right ventricular pacing; Stunned myocardium.

Mobilization of Endothelial Progenitor Cells Following Creation of Arteriovenous Access in Patients with End-Stage Renal Disease.

BACKGROUND: A patent arteriovenous (AV) fistula induces activation of regional vascular endothelium and vascular shear force. Shear stress is an important physiological force in mobilizing endothelial progenitor cells (EPCs). This study aimed to explore the perioperative changes of circulating EPC levels for patients who require hemodialysis and underwent radiocephalic fistula operation. METHODS: This prospective cohort study included patients who received a radiocephalic fistula surgery when they were between 25 and 65 years of age. The subjects were followed for 90 days postoperatively for any stenotic events or immaturity of the fistula. Blood samples were obtained on the day before surgery and at postoperation day (POD) 3 and 30. CD133+/KDR+ cells, defined as EPCs, were analyzed using flow cytometry. Blood flow of the fistula was followed on POD 3 and 30. RESULTS: A total of 30 patients were enrolled in the study from July 2009 to December 2011. One patient dropped out of the study and seven patients developed a stenotic (or immature) AV fistula (7/29, 24.1%). There were positive linear relationships between EPC numbers and shear rate postoperatively, which were more significant on POD 30. In addition, postoperative mobilization of EPCs was significantly higher in patients who developed a stenotic fistula than those without. CONCLUSIONS: The mobilization of circulating EPCs correlated with a compromised arteriovenous fistula. The biological significance of increased EPC numbers need to be determined in future studies. KEY WORDS: Arteriovenous fistula; Endothelial progenitor cells.

Mycotic aneurysms in the abdominal aorta and iliac arteries: CT-based grading and correlation with surgical outcomes.

BACKGROUND: Computed tomography (CT) is the modality of choice in the diagnosis of mycotic aneurysms. The present study aimed to classify the CT findings of mycotic aneurysms, and to assess their predictive value based on the correlation of a CT-based grading system with prognostic factors and outcomes. METHODS: Over the past 21 years, 40 consecutive patients underwent open surgery for mycotic aneurysms of the abdominal aorta and iliac arteries in our hospital. The CT appearances of mycotic aneurysms were categorized into four grades: grade 1, periarterial changes without destruction of the arterial wall; grade 2, presence of saccular outpouching; grade 3, extensive retroperitoneal infection; and grade 4, massive perianeurysmal hemorrhage. Clinical data were recorded for analysis. RESULTS: The surgical mortality and overall aneurysm-related mortality rates were 17.5 and 25%, respectively. The poor prognostic predictors were shock, rupture, and concomitant gastrointestinal procedures. The increasing proportions of shock and rupture status corresponded to mycotic aneurysms of higher grades in the CT-based grading. In addition, one patient in grades 1 and 2, versus five in grades 3 and 4 (P = 0.02), required concomitant gastrointestinal procedures. The CT-based grading exhibited a strong association with surgical mortality (Cramer's V coefficient = 0.65; P = 0.002) and a relatively strong association with overall aneurysm-related mortality (Cramer's V coefficient = 0.53; P = 0.01). CONCLUSIONS: For patients surgically treated for abdominal mycotic aneurysms, the CT-based grading is correlated with clinical severity, surgical complexity, and outcomes, and thus it may serve as a simple scale for risk classification.

Surgical Treatment of Pseudoaneurysm of Innominate Artery Infected with Burkholderia Pseudomallei.

UNLABELLED: The management of melioidosis, caused by Burkholderia pseudomallei, presenting as an infected pseudoaneurysm requires radical debridement and prolonged antibiotics because the pathogen is resistant to host immunity. An extra-anatomical bypass might be a better treatment choice than in situ graft interposition or other methods.We report on a 76-year-oldman with an infected pseudoaneurysmlocated in the innominate artery and a method of extra-anatomical bypass that has not yet been reported in the literature. The patient recovered well without recurrence of infection after the surgical procedure. KEY WORDS: Burkholderia pseudomallei; Extra-anatomical bypass; Innominate artery; Melioidosis; Pseudoaneurysm.

Aortic root remodeling after surgical repair of acute type A aortic dissection using different anastomosis techniques.

Background: After surgical repair of acute type A aortic dissection (aTAAD), remodeling of the residual aortic segments is the key outcome parameter associated with late reoperation or aorta-related adverse events. In this study, we analyzed the surgical outcomes of aTAAD using either a telescopic or continuous anastomosis technique, focusing on their impact on aortic root remodeling during the longitudinal follow-up. Methods: Between 2012 and 2018, 112 surgical repairs of aTAAD with ascending aorta replacement and without aortic arch or aortic root replacement were performed. The medical records were reviewed retrospectively, and early and late outcomes were compared between the telescopic and continuous anastomosis techniques. The generalized estimating equation method was used to analyze the effects of different anastomosis techniques on serial aortic root remodeling. Results: The telescopic anastomosis technique was used in 46 cases (41.1%), and the conventional continuous anastomosis technique was used in 66 cases (58.9%). There were no differences in in-hospital mortality or the incidence of major complications between the groups. The telescopic anastomosis group demonstrated stable postoperative regression of the aortic root diameter during follow-up. In contrast, the continuous anastomosis group showed a progressive dilatation of the aortic root. There was a trend toward better aortic root adverse event-free survival rates in the telescopic anastomosis group (P = .081). Conclusions: The telescopic anastomosis technique is a safe alternative to the continuous anastomosis technique in the surgical repair of aTAAD, with comparable early results. In addition, telescopic anastomosis was associated with beneficial aortic root remodeling in the medium term compared with continuous anastomosis.

Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction.

Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function-especially when strained-and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.

Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs.

BACKGROUND: Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. METHODS AND RESULTS: A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10(8) isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and -dP/dt (1214.5±91.9 and -1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and -1809.6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm(2) in MI+MNCs and 229.4±41.4 cells/mm(2) in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. CONCLUSIONS: We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

Outcomes of acute type A aortic dissection operations performed by early-career cardiovascular surgeons.

Objective: Surgical outcomes of acute type A aortic dissection have been recognized to be associated with the surgical volume of individual hospitals and surgeons. In this study, we aimed to investigate the results and learning curves of acute type A aortic dissection operations performed by early-career cardiovascular surgeons. Methods: A total of 248 surgical repairs of acute type A aortic dissections were conducted at a tertiary medical center between 2010 and 2018. By using the cumulative sum test, cardiovascular surgeons in their early career were identified, and their performances were assessed. The outcomes of patients who were operated by early-career cardiovascular surgeons were compared with those by experienced or senior surgeons. Results: During the study period, 202 (81.5%) of the 248 acute type A aortic dissection operations were performed primarily by the 4 newly appointed attending cardiovascular surgeons. In cumulative sum curves, all surgeons exhibited a steady performance throughout the study period. On the basis of our institutional result of acute type A aortic dissection operation, early career was defined as performing fewer than 32 acute type A aortic dissection operations. The 30-day mortality rates of acute type A aortic dissection operations performed by early-career surgeons were equivalent to those performed by experienced/senior surgeons (10.9% vs 12.5%, P = .844). There was also no difference in mid-term overall survival and aortic event-free survival between the 2 groups (P = .638 and P = .574, respectively). Conclusions: In a center with a well-established program, cardiovascular surgeons could accomplish surgical repair of acute type A aortic dissection with adequate early- and mid-term results from the initiation of their careers.

Simultaneous Thrombolysis and Extracorporeal Membrane Oxygenation for Acute Massive Pulmonary Emboli.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used in patients with circulatory collapse or extremely unstable hemodynamics caused by acute massive pulmonary embolism (PE). The effectiveness of simultaneous thrombolytic therapy has been rarely investigated in these patients after being stabilized with ECMO. METHODS: From January 2008 to December 2018 consecutive patients with acute massive PE requiring ECMO supported in a tertiary medical center were included for retrospective analysis. RESULTS: Thirteen patients with PE underwent ECMO implantation and received subsequent thrombolytic therapy as a definite treatment for PE. All patients survived their ECMO courses to a successful decannulation, with a mean ECMO support duration of 6.23 ± 4.69 days. Eleven patients (84.62%) survived to hospital discharge. All survivors were alive during follow-up, although 2 patients (18.2%) had permanent dysfunctional neurologic complications. Major bleeding complications occurred in 4 patients (30.77%), whereas no patient had intracranial hemorrhage. Systemic thrombolysis showed comparable outcomes of catheter-directed thrombolysis in our patients who underwent ECMO. CONCLUSIONS: Thrombolysis-based therapeutic strategy under ECMO could be a relatively safe and effective definitive treatment for patients with acute massive PE, even for those who were resuscitated. Bleeding complications remain a major concern and should be monitored and managed immediately.

The efficacy of aortic stent grafts in the management of mycotic abdominal aortic aneurysm-institute case management with systemic literature comparison.

BACKGROUND: Conventional surgery (CS) for treatment of mycotic aortic aneurysm has rather high surgical morbidity and mortality rates. The use of endovascular aortic repair (EVAR) might simplify the procedure and provide a good alternative for this critical condition, but this remains to be proved. We analyzed all mycotic abdominal aortic aneurysm (AAA) cases treated by CS or EVAR in our institute and the reported cases treated by EVAR from the literature to determine the risk factors for aneurysm-related mortality and morbidity and to clarify the efficacy of the EVAR technique. METHODS AND RESULTS: All relevant literature reports of EVAR management of mycotic AAA and all cases treated in our institute, 41 cases, were included and analyzed. Of the 20 cases treated by EVAR, one had early mortality (1/20, 5%); of the remaining 21 cases that received CS, the early mortality rate was 4.8% (1/21). Patients in the CS group had a higher late mortality rate than those in the EVAR group (45% vs. 10.5%, p<0.05). However, the 24-month actual survival rate and actuarial aneurysm-related event-free rate were 83.9+/-8.6% and 78.3+/-9.7%, respectively, for the EVAR group and did not significantly differ from the CS group (70.4+/-10.2% and 80.1+/-8.9%). The significant predictors for aneurysm-related mortality and morbidity were age, Salmonella species infection, and leukocytosis, and possibly aortoenteric fistula and shock, but not the EVAR or CS procedures themselves. CONCLUSION: Compared with CS, EVAR might be an alternative strategy for managing mycotic AAAs.