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Conventional aortic root and valve-sparing root replacement surgery are two current surgical treatments for aortic dilatation syndromes. This review article aims to review the current literature surrounding these two established techniques.This review article will address the current indications for valve-sparing root replacement surgery, technical considerations in surgical planning and a comparison of clinical outcomes between these two surgical techniques.Valve-sparing root replacement surgery is a safe and established treatment for aortic syndromes. Valve-sparing surgery procedure avoids the inherent risk of prosthetic valve dysfunction and prosthesis infection by preserving the native aortic valve compared to conventional aortic root surgery. This has been demonstrated in various observational studies and should be considered in clinically and anatomically appropriate patients. Other technical considerations, such as reimplantation versus remodelling technique and aortic cusp repair in select patients, may impact in short-term procedural and long-term clinical success with valve-sparing surgery.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Trans-apical approach has been proved successful in failing surgical bio-prosthesis in both mitral and aortic position in adult patients. Recently, valve-in-valve treatments have been applied even in patients with complex congenital heart disease. Here, we report the case of a 32 years old lady with left atrial isomerism, complete AV septal defect, interrupted inferior vena cava with azygos continuation who underwent Kawashima procedure with atrial Fontan. Severe systemic atrioventricular valve regurgitation necessitated a 33 mm Perimount valve implantation and conversion to lateral tunnel Fontan. After only 4 years there was severe valve stenosis and the patient underwent successful trans-apical transcatheter implantation of a 29 mm Sapien valve.

Background: For stage III or IVa thymic tumours, a multimodality approach is recommended. The role of surgery is to achieve complete resection. Aim: To present the outcomes of patients undergoing surgery for stage III or IVa thymoma. Methods: Retrospective review of patients undergoing open surgery for stage III or IVa thymoma between 2016 and 2020 at a single centre was performed. Preoperative imaging, treatment plan, surgical approach, and postoperative outcomes were analyzed. Results: Forty-seven patients underwent surgery for thymoma. Patients with clinical stage I/II thymoma or minimally invasive thymectomy were excluded. Thirteen patients with clinical stage III or IVa were included. Median sternotomy approach was used in four patients, of which one was redo sternotomy; a hemi-clamshell in four; and a combination of approaches in the remaining five patients. There was no postoperative mortality. Four patients had postoperative complications. Complete resection was achieved in all but two patients. At a median follow-up of 17.9 months, all patients were alive with no evidence of recurrence except one who died 4 months after surgery from coronavirus disease 2019 (COVID-19) pneumonia. Conclusions: Surgery for stage III and IVa thymoma is safe and can be achieved with complete macroscopic resection. To obtain adequate exposure of all structures involved in the tumour, combined surgical approaches can be used with no increased morbidity. The majority of patients, even after extrapleural pneumonectomy, did not receive adjuvant radiotherapy and had no evidence of local relapse.

AimsDurability of transcatheter aortic valve implantation (TAVI) is key to its expansion. We sought to identify incidence of valve thrombosis and predictors of valve thrombosis in our single centre with associated coagulation testing pre-TAVI and post-TAVI.Methods and resultsThis single-centre observational study comprised patients undergoing transfemoral TAVI discussed in the Heart Team meeting . Patients were followed up with echocardiography at 120 days to identify incidence of elevated transvalvular gradient and multivariable analysis was performed to identify factors associated with an increased odds of developing valve thrombosis. In addition, 11 patients underwent baseline, day 1 and day 120 post-TAVI coagulation testing. Between August 2017 and August 2019, 437 consecutive patients underwent transfemoral TAVI. Of these patients, 207/437 (47.4%) had 3-month follow-up echo data available and were analysed. Of these patients, 26/207 (12.6%) had elevated transvalvular gradients. These patients tended to be younger (80±14 vs 83±6 years; p=0.047) with a lower ejection fraction (49±13 vs 54%±11%; p=0.021), with a greater proportion of the population experiencing atrial fibrillation (14/21, 54% vs 68/181, 38%; p=0.067). Following multivariable analysis, there remained a trend towards higher eccentricity index associated with elevated gradients. Baseline (pre-TAVI) elevation of thrombin antithrombin levels (56±63; reference range 1.0–4.1 ng/L) and PF 1+2 (791±632; reference range 69–229 ng/mL) normalised at 120 days post-TAVIConclusionThis study demonstrated that in the cohort of patients undergoing transfemoral TAVI in our centre: younger age, poor ejection fraction, atrial fibrillation and increased baseline eccentricity of the aortic valve annulus were present to a greater extent in patients exhibiting elevated transvalvular gradients at 3-month follow-up. Further work is required to delineate the extent of coagulation derangement and confirm predictors of thrombosis.

Multimodality imaging is of imperative value for the planning and guidance of transcatheter mitral valve interventions. This review employs the value of different imaging modalities and future implications for clinical practice.

The aim of the study was to assess the degree of aerosolisation in different chest drainage systems according to different air leak volumes, in a simulated environment. This novel simulation model was designed to produce an air leak by passing air through and agitating a fluorescent fluid. The air leak volume and amount of fluorescent fluid were tested in various combinations and aerosolisation was assessed at 10-minute intervals using the ultraviolet light. The following chest drainage systems were compared: (1) single-chamber chest drainage system, (2) 3-compartment wet-dry suction chest drainage system, (3) digital drainage and monitoring system. The impact of suction (−2 and −4 kPa) in generating aerosolised particles was tested as well. A total number of 187 of 10-minute interval measurements were performed. The single-chamber chest drainage system generated the largest number of aerosolised particles at different air leak volumes and drainage output. The 3-compartment wet-dry suction system and the digital drainage and monitoring system did not generate any identifiable aerosolised particles at any of the air leak or drain output volumes considered. Suction applied to the chest drainage systems did not have an effect on aerosolisation. Aerosol generation in the simulated air-leak model demonstrated the potential risk of SARS-CoV-2 spread in the clinical setting. Full personal protective equipment must be used in patients with an air leak. Single-chamber chest drainage system generates the highest rate of aerosolised particles and it should not be used as an open system in patients with an air leak., Graphical Abstract Image, graphical abstract

Patients with multi-vessel coronary artery disease and poor left ventricular (LV) function (ejection fraction [EF] 30%) requiring revascularization are considered 'high-risk'. Limited long-term survival data exists comparing percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) versus surgery for this cohort of patients.We retrospectively reviewed our data for 321 patients with EF30% who underwent multi-vessel revascularization from January 2005 to December 2015 using Cox regression analyses and inverse probability treatment weighted (IPTW) methods. We stratified patients that underwent surgical revascularization into on-pump coronary artery bypass grafting (CABG) and off-pump CABG and analyzed all-cause mortality at 10 years compared to PCI.214 patients underwent CABG (n [on-pump CABG] = 94; n [off-pump CABG] = 120) and 107 patients had PCI with second generation DES. PCI with DES had higher 10-year mortality compared with on-pump CABG (Hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.46-2.42; p 0.001) and off-pump CABG (HR = 2.32, 95% CI = 1.75-3.15; p 0.001). This was confirmed in IPTW analyses. When adjusting for both measured and unmeasured factors using instrumental variable analyses, PCI with DES had higher 10-year mortality compared with on-pump CABG (Δ = 13.5, 95% CI = 3.2-24.5; p = 0.012) and off-pump CABG (Δ = 16.1, 95% CI = 5.9-25.8; p 0.001).Surgical revascularization, preferably off-pump CABG, results in better long-term survival compared with PCI using second generation DES for patients with multi-vessel coronary artery disease and poor left ventricular function. Randomized controlled trials in this patient group should be undertaken.

Double-outlet left ventricle (DOLV) is an extremely rare type of ventriculoarterial connection, mostly reported anecdotally with wide variations in morphology, surgical strategy and clinical outcome. The aim of the present study was to define current morbidity and mortality of biventricular repair and discuss surgical management in infancy. Inclusion criteria were English literature publication; balanced ventricular development and completion of biventricular repair. Institutional experience was also reported. Study end points were survival and freedom from cardiovascular events. Univariate analysis to identify risk factors for complications was performed. During a 45-year interval, 37 cases of DOLV were identified. Median age at repair was 48 months (range 0.3–336); seven patients were infants. Extracardiac repair was performed in 21 (57%) patients, right ventricular outflow patch in seven, pulmonary translocation in six, and intraventricular repair in three. There were three (8%) hospital deaths, due to right heart failure, and seven (21%) patients experienced 10 perioperative complications. Univariate analysis showed year of operation (P = 0.02) and outflow patch technique (P = 0.003) as risk factors for hospital morbidity and mortality. During a median follow-up of 26 months (range 1–192), there was one death and seven reoperations. Ten-year survival and freedom from adverse cardiovascular events were 87 ± 6 and 70 ± 10%, respectively. Although seldom reported in the past, repair of DOLV in infancy does not increase surgical risk. Early and late morbidity are mostly due to right heart complications and more common after right ventricular outflow patch repair. Paucity of follow-up information may underestimate actual late adverse event rate.

Transcatheter aortic valve implantation (TAVI) is now routinely performed to treat inoperable and high-risk patients with severe aortic stenosis (AS). Transapical or transaortic approaches are alternative routes used when peripheral accesses are unsuitable. Correct placement of the device is achieved with the help of an angiography performed with a pigtail catheter to identify the deployment view. However, in patients with severe vascular disease, placement of a pigtail catheter may not be possible. We report a modified single-puncture technique, whereby a single access point is used to perform both angiography and TAVI by using visible calcification landmarks as reference points.

OBJECTIVE: Children undergoing Ross operation were expected to have longer autograft, but shorter homograft durability compared with adults. In order to define the outcome in the second decade after Ross operation in children, a nationwide review of 23 years of experience was undertaken. METHODS: 305 children underwent Ross operation in 11 paediatric units between 1990 and 2012. Age at surgery was 9.4±5.7 years, indication aortic stenosis in 103 patients, regurgitation in 109 and mixed lesion in 93. 116 (38%) patients had prior procedures. Root replacement was performed in 201 patients, inclusion cylinder in 14, subcoronary grafting in 17 and Ross-Konno in 73. RESULTS: There were 10 (3.3%) hospital and 12 late deaths (median follow-up 8.7 years). Survival was 93±2% and 89±3% and freedom from any reoperation was 76±3% and 67±6% at 10 and 15 years. 34 children had autograft 37 reoperations (25 replacement, 12 repair): three required transplantation after reoperation. Freedom from autograft reoperation was 86±3% and 75±6% at 10 and 15 years. 32 children had right heart redo procedures, and only 25 (78%) conduit replacements (15-year freedom from replacement, 89±4%). Prior operation (p=0.031), subcoronary implant (p=0.025) and concomitant surgical procedure (p=0.004) were risk factors for left heart reoperation, while infant age (p=0.015) was for right heart. The majority (87%) of late survivors were in NYHA class I, 68% free from medication and six women had pregnancies. CONCLUSIONS: Despite low hospital risk and satisfactory late survival, paediatric Ross operation bears substantial valve-related morbidity in the first two decades. Contrary to expectation, autograft reoperation is more common than homograft.

A 21-year-old woman affected by a rare autosomal-dominant disorder called Singleton-Merten syndrome [(1)][1] with symptomatic severe aortic regurgitation in New York Heart Association functional class III was referred for consideration of aortic valve intervention. Her clinical history was

Cardioplegic arrest is a model of ischemia/ reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modula- tion of apoptosis after ischemia and reperfusion. Angio- tensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfu- sion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dul- becco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) car- dioplegic solution (Group 2); cold (4°C) MSTH2 cardiople- gic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia deliv- ery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P < 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1b (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 recep- tor antagonist supplemented with cold MSTH2 signifi- cantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influ- ence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotec- tive effect and cardiac recovery in neonates and infants. Key Words: Neonatal rat myocytes— Cardioplegia—Angiotensin II antagonist—Signal trans- ducers and activators of transcription.

Progress in biomaterial technology and improvements in surgical and perfusion strategy ameliorated morbidity and mortality in pediatric cardiac surgery. In this study, we describe our clinical experience comparing performance of two neonatal oxygenators. From January 2002 to March 2011, 159 infants with less than 5 kg body weight underwent heart surgery. Ninety-four patients received a D901 Lilliput 1 oxygenator with standard bypass circuit (group A), while 65 received a D100 Kids with miniaturized bypass circuit (group B). Miniaturization consisted in shortened arterial, venous, cardioplegia, and pump-master lines. Priming composition consisted in Ringer's acetate solution with addition of albumin and blood, with target hematocrit of 24% or greater. In group B cardiopulmonary bypass (CPB) was vacuum-assisted and started with an empty venous line. Modified ultrafiltration and Cell-Saver blood infusion was routinely applied in both groups. Average ± standard deviation (SD) age at repair was 37 ± 38 days in group A and 59 ± 60 days in group B (P = 0.005). Average ± SD weight, height, and body surface area were 3.5 ± 0.7 kg, 52 ± 4 cm, and 0.22 ± 0.03 m(2) , respectively, in group A, and 3.7 ± 1 kg, 53 ± 5 cm, and 0.23 ± 0.02 m(2) , respectively, in group B (P = not significant [NS]). Male sex was predominant (55 vs. 58%, P = NS). Priming volume was 524 ± 67 mL (group A) and 337 ± 53 mL (group B) (P = 0.001). There were no statistical differences in hemoglobin at the start, during, and at the end of CPB, but group A required higher blood volume added to the prime (111 ± 33 vs. 93 ± 31 mL, P = 0.001). In group B, two surgical procedures were completed in total hemodilution. In group B, CPB time and aortic cross-clamp time were shorter than in group A (106 ± 52 vs. 142 ± 78 min and 44 ± 31 vs. 64 ± 31 min, respectively, P = 0.001). There were 16 hospital deaths in group A and 4 in group B (P = 0.04). Durations of mechanical ventilation and intensive care unit stay were 5.3 ± 3.2 vs. 4.1 ± 3.2 days (P = 0.02) and 6.5 ± 4.9 vs. 5.1 ± 3 days (P = 0.03), respectively. There were significant differences in inotropic score (1083 ± 1175 vs. 682 ± 938, P = 0.04) and blood postoperative transfusion (153 ± 226 vs. 90 ± 61 mL, P = 0.04). Twenty-seven patients in group A and 10 in group B presented with major adverse postoperative complications (P = 0.04). Use of neonatal oxygenators with low priming volume, associated with a miniaturized bypass circuit, seems to be a favorable strategy to decrease postoperative morbidity after cardiac surgery in neonates and infants.

Temporary tricuspid valve detachment improves the operative view of certain congenital ventricular septal defects (VSDs), but its long-term effects on tricuspid valve function are still debated.From 2002 through 2012, we performed a prospective study of 68 children (mean age, 1.28 ± 1.01 yr) who underwent transatrial closure of VSDs following temporary tricuspid valve detachment. Sixty patients had conoventricular and 8 had mid-muscular VSDs. All were in sinus rhythm. Seventeen patients had systemic pulmonary artery pressures. Preoperative echocardiograms showed trivial-to-mild tricuspid regurgitation in 62 patients and tricuspid dysplasia with severe regurgitation in 6 patients. Patients were clinically and echocardiographically monitored at 30 postoperative days, 3 months, 6 months, every 6 months thereafter for the first 2 years, and then once a year.No in-hospital or late death was observed at the median follow-up evaluation of 5.9 years. Mean intensive care unit and hospital stays were 1.6 ± 1.1 and 7.3 ± 2.7 days, respectively. Residual small VSDs occurred in 3 patients, and temporary atrioventricular block in one. After VSD repair, 62 patients (91%) had trivial or mild tricuspid regurgitation, and 6 moderate. Five of these last had severe tricuspid regurgitation preoperatively and had undergone additional tricuspid valve repair during the procedure. The grade of residual tricuspid regurgitation remained stable postoperatively, and no tricuspid stenosis was documented. All patients were in New York Heart Association class I at follow-up.Temporary tricuspid valve detachment is a simple and useful method for a complete visualization of certain VSDs without incurring substantial tricuspid dysfunction.

Here reported is an unusual case of pulmonary artery band migration with serendipitous clinical presentation late after neonatal palliation of single ventricle with aortic arch hypoplasia. The diagnostic and therapeutic implications are discussed.

Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mecha- nism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role.To inves- tigate this hypothesis, we examined the effects of angioten- sion II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the down- stream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohy- pertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langen- dorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 car- dioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antago- nist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investi- gated in Western blot studies. Times to arrest after car- dioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfu- sion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a signifi- cant reduction in STAT2 and STAT5 tyrosine phosphory- lation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supple- mented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1b (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflamma- tory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart. Key Words: Rat myocardium— Cardioplegia—Angiotensin II antagonist—Valsartan— Signal transducers and activators of transcription.

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates

The association between truncus arteriosus and total anomalous pulmonary venous return is exceedingly rare. Here described is a neonate presenting with a common arterial trunk and a previously unreported "scimitar-like" mixed total pulmonary venous return who underwent a successful one-stage repair. The unprecedented anatomic pattern of the systemic and pulmonary venous connection and the original surgical strategy are discussed.

Angiotensin II was reported to induce insulin-like growth factor-I and endothelin-1 gene expression and peptide release by ventricular cardiomyocytes. However, the progression from cardiac hypertrophy to failure in humans is characterized by a reduced myocyte expression of insulin-like growth factor-I and endothelin-1, notwithstanding the enhanced cardiac generation of angiotensin II. In the present study we investigated the functional status of the signaling pathways responsible for angiotensin II-induced endothelin-1 and insulin-like growth factor-I formation in human ventricular myocytes isolated from patients with dilated (n = 19) or ischemic (n = 14) cardiomyopathy and nonfailing donor hearts (n = 6).In human nonfailing ventricular myocytes, angiotensin II (100 nmol/l) induced insulin-like growth factor-I and endothelin-1 gene expression, and peptide release was mediated by extracellular signal-regulated kinase activation and inhibited by extracellular signal-regulated kinase antagonism (PD98059, 30 micromol/l), endothelin-1 formation being partially reduced also by c-Jun N-terminal kinase inhibition (SP600125, 10 micromol/l); insulin-like growth factor-I and endothelin-1 formations were unaffected by the inhibition of p38 mitogen-activated protein kinase (SB203580, 10 micromol/l) and Janus tyrosine kinase 2 (AG490, 10 micromol/l). In failing myocytes, angiotensin II failed to induce insulin-like growth factor-I and endothelin-1 formation; angiotensin II-induced extracellular signal-regulated kinase activation was significantly impaired (-88% vs. controls) although c-Jun NH2-terminal kinase activation was preserved. The impaired extracellular signal-regulated kinase phosphorylation in failing myocytes was associated with increased myocyte levels of mitogen-activated protein kinase phosphatases.Therefore, the altered growth factor production in failing myocytes is associated with a significant derangement in intracellular signaling.

Hyperglycemia was reported to enhance angiotensin (Ang) II generation in rat cardiomyocytes, and Ang II inhibition reduces cardiovascular morbidity and mortality in diabetic patients. In diabetic patients, the enhanced activation of intracellular pathways related with myocyte hypertrophy and gene expression might enhance the progression of cardiac damage. Therefore, we investigated the effects of glucose on Ang II–mediated activation of Janus-activated kinase (JAK)-2, a tyrosine kinase related with myocyte hypertrophy and cytokine and fibrogenetic growth factor overexpression, in ventricular myocytes isolated from nonfailing human hearts (n = 5) and failing human hearts (n = 8). In nonfailing myocytes, JAK2 phosphorylation was enhanced by Ang II only in the presence of high glucose (25 mmol/l) via Ang II type I (AT1) receptors (+79% vs. normal glucose, P < 0.05). JAK2 activation was prevented by inhibitors of reactive oxygen species (ROS) generation (diphenyleneiodonium [DPI], tiron, and apocynin). In myocytes isolated from failing hearts, JAK2 phosphorylation was enhanced by high glucose alone (+107%, P < 0.05). High glucose–induced JAK2 activation was blunted by both ACE inhibition (100 nmol/l ramipril) and AT1 antagonism (1 μmol/l valsartan), thus revealing that the effects are mediated by autocrine Ang II production. Inhibition of ROS generation also prevented high glucose–induced JAK2 phosphorylation. In conclusion, in human nonfailing myocytes, high glucose allows Ang II to activate JAK2 signaling, whereas in failing myocytes, hyperglycemia alone is able to induce Ang II generation, which in turn activates JAK2 via enhanced oxidative stress.

Cardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment.

OBJECTIVES: Plasma concentration of procalcitonin (PCT) and its value in the diagnosis of infection in paediatric patients treated with extracorporeal membrane oxygenation (ECMO) are undefined. This study aimed to define the levels of PCT and C-reactive protein (CRP) in paediatric cardiac ECMO patients and to determine their role in predicting infection, severity of organ dysfunction and clinical outcome. METHODS: PCT and CRP plasma concentrations were measured daily in 20 consecutive infants and young children treated with venoarterial ECMO. Each patient was examined daily for signs of infection and multiple organ dysfunction syndrome (MODS). A total of 139 patient days were classified for infection and MODS. RESULTS: The median PCT and CRP plasma concentrations were not increased during infection: 2.4 vs 8.8 ng/ml and 223.8 vs 240.6 mg/l, in patients with vs without infection, respectively. PCT, but not CRP, was significantly elevated during MODS (10.9 vs 1.85 ng/ml) (P= 0.001). The area under the receiver operating characteristic (ROC) curve was 0.984 for PCT (95% confidence interval [CI], 0.962– 1.000) compared with 0.347 for CRP (95% CI, 0.211–0.484) (P= 0.001). Only PCT differed significantly in patients weaned from ECMO who survived (2.6 ng/ml) vs patients not weaned from ECMO (10.5 ng/ml) (P= 0.001). The area under the ROC curve was 0.871 (95% CI, 0.786–0.956) compared with 0.261 for CRP (95% CI, 0.145–0.377) (P= 0.001). CONCLUSIONS: Neither PCT nor CRP are reliable markers of infection in paediatric cardiac ECMO patients. However, high levels of PCT are associated with MODS. PCT may be used as a prognostic indicator of clinical outcome in this high-risk population.

OBJECTIVE Autograft valve and root pathology is the leading cause of Ross procedure failure. To define risk and outcome of autograft valve/root repair at reoperation, a 17-year experience was analysed. METHODS One hundred and thirty-two consecutive late survivors underwent cross-sectional clinical and echocardiographic examination on average 10.8 ± 14.7 years (range 0.4-17) after Ross procedure. Study endpoints were hospital and late morbidity, freedom from autograft reoperation, freedom from root/valve replacement and functional outcome after valve/root repair. RESULTS Twenty-seven (20%) patients underwent 33 cardiac reoperations, the first on average 7.7 ± 4.5 years (range 0.08-16.2) after Ross operation. Nineteen had undergone root replacement, 5 inclusion cylinder and 3 subcoronary grafting. Indication was root pathology in 17 (63%) patients and isolated valve in 10. Surgery consisted in valve repair/sparing in 17 patients and valve/root replacement in 10, with no hospital mortality. Freedom from any autograft valve/root reoperation was 74 ± 5% at 15 years. No patient with valve/root replacement required second reoperation. Instead, 6/17 (35%) patients having autograft valve repair/sparing and followed for 4.2 ± 2.9 years (range 0.3-10.8) required re-repair/AVR, while 11 present mild AI or less. Freedom from autograft valve/root replacement was 83 ± 5% at 15 years. At multivariate analysis, predictors of reoperation were age at Ross (P = 0.002) and use of root technique (P = 0.049). Failure of autograft valve repair/sparing was associated with isolated valve pathology (P = 0.014) and earlier reoperation (P = 0.002). Pre-repair autograft insufficiency was significant at univariate analysis only (P = 0.01). CONCLUSIONS Autograft reoperation carries negligible hospital risk. Pulmonary valve sparing or repair is feasible in half of patients with Ross failure. Concomitant root remodelling and absence of preoperative severe valve dysfunction predict successful and durable repair.

Background Repair of congenital aortic valve (CAV) lesions may be achieved by creation of either tricuspid or bicuspid valve morphology. To define feasibility and outcome of CAV repair by bicuspidization a 10-year experience was reviewed. Methods Between January 2002 and December 2011, 147 consecutive patients underwent operation for CAV insufficiency; 58 had valve or root repair (group 1) and 89 had valve or root replacement (group 2). Patients having repair were younger (42.9 vs 51.3 years, p = 0.001), with lesser prevalence of severe insufficiency (72% vs 90%, p = 0.002). In patients having repair, morphology of CAV was bicuspid in 51, monocuspid in 4, and quadricuspid in 3, whereas in the replacement group it was bicuspid in 87 and quadricuspid in 2 ( p = 0.04). Surgery consisted of an isolated aortic valve procedure in 20 versus 45 patients, associated with aortic root or ascending aortic repair in 38 versus 44 patients, in group 1 versus 2 ( p = 0.04). Results There were no hospital and 3 late deaths during a mean follow-up of 3.8 ± 2.5 years (range 0.2 to 10.0). Eight-year survival (89% ± 10% vs 97% ± 2% [ p = 0.7]), freedom from valve-related events (84% ± 10% vs 89% ± 4% [ p = 0.8]), and freedom from aortic valve reoperation (95% ± 3% vs 93% ± 3% [ p = 0.6]) were comparable. Risk factors for reoperation at univariate analysis were isolated valve surgery ( p = 0.001), Ross operation ( p = 0.001), and endocarditis ( p = 0.002). Follow-up echocardiography of repair patients showed mild or less aortic insufficiency in 51 (88%) and mild or less stenosis in 57 (98%). Conclusions Valve repair by preservation or creation of bicuspid morphology is feasible in almost half of all comers with CAV insufficiency, with satisfactory and stable midterm functional outcome. Rates of valve-related adverse events and reoperation are similar to those of patients having replacement.

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates2.0 kg). A cardioplegia delivery system was inserted into the aortic root. Under moderate hypothermia, ascending and descending aorta were cross-clamped, and "beating heart and brain" aortic arch repair was performed. Arch repair was composed of patch augmentation in five, end-to-side anastomosis in three, and replacement in two patients. Average cardiopulmonary bypass time was 163 ± 68 min (71-310). In two patients only (one HLHS, one complex single ventricle), a period of cardiac arrest was required to complete intracardiac repair. In such cases, antegrade blood cardioplegia was delivered directly via the same catheter used for selective myocardial perfusion. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 39 ± 18 min (17-69). Weaning from cardiopulmonary bypass was achieved without inotropic support in three and with low dose in seven patients. One patient required veno-arterial extracorporeal membrane oxygenation. Four patients, body weight3.0 kg, needed delayed sternal closure. No neurologic dysfunction was noted. Renal function proved satisfactory in all, while liver function was adequate in all but one. The present experience suggests that selective and independent cerebro-myocardial perfusion is feasible in patients with complex or recurrent aortic arch disease, starting from premature newborn less than 2.0 kg of body weight to adults. The technique is as safe as previously reported methods of cerebro-myocardial perfusion and possibly more versatile.

An altered thyroid hormone profile has been reported in patients with congestive heart failure. However, information regarding the status of thyroid hormone receptors in human failing cardiomyocytes is lacking. Therefore the expression of thyroid hormone and beta-adrenergic receptors was investigated in human ventricular cardiomyocytes isolated from patients with end-stage heart failure (FM, n=12), or from tentative donors (C, n=4). The expression of thyroid (TRalpha1, and TRbeta1) and beta-adrenergic receptors (ARB1 and ARB2) was measured at both the gene, and at the protein level. In FM the reduced mRNA expression of ARB1 (p

Although angiotensin (Ang)II-induced Janus-activated kinase (JAK)2 phosphorylation was reported to be enhanced in failing human cardiomyocytes, the downstream balance between cardio-protective (signal transducer and activator of transcription-STAT3) and the pro-inflammatory (STAT2 and STAT5) response remains unexplored. Therefore STATs phosphorylation and putative genes overexpression following JAK2 activation were investigated in isolated cardiomyocytes obtained from failing human hearts (n = 16), and from non-failing(NF) hearts of humans (putative donors, n = 6) or adult rats. In NF myocytes Ang II-induced JAK2 activation was followed by STAT3 phosphorylation (186 ± 45% at 30 min), with no STAT2 or STAT5 response. The associated B cell lymphoma (Bcl)-xL overexpression (1.05 ± 0.39 fold) was abolished by both JAK2 and extracellular signal-regulated kinase (ERK)1/2 inhibitors (AG490, 10 μM, and PD98059, 30 μM, respectively), whereas Fas ligand (Fas-L) response (0.91 ± 0.21 fold) was inhibited only by p38MAPK antagonism (SB203580, 10 μM). In failing myocytes Ang II-induced JAK2 activation was followed by STAT2 (237 ± 38%) and STAT5 (222 ± 31%) phosphorylation, with no STAT3 response. No changes in Bcl-xL expression were observed, and the associated Fas-L gene overexpression (1.14 ± 0.27 fold) being abolished by p38 mitogen-activated protein kinase (MAPK) antagonism. The altered JAK2 induced STATs response in human failing cardiomyocytes may be of relevance for the progression of cardiac dysfunction in heart failure.