Predictors of Outcome in Patients with Pulmonary Hypertension Undergoing Mitral and Tricuspid Valve Surgery.

Background and Objectives: Pulmonary hypertension (PH) secondary to left-sided valvular heart disease is associated with poor cardiac surgical outcome compared with patients without PH. Our objective was to investigate the prognostic factors of surgical outcome in patients with PH undergoing mitral valve (MV) and tricuspid valve (TV) surgery, in order to risk stratify their management. Materials and Methods: This is a retrospective observational study on patients with PH who underwent MV and TV surgery from 2011 to 2019. The primary outcome was all-cause mortality. The secondary outcomes were post-op respiratory and renal complications, length of intensive care unit stay and length of hospital stay. Results: Seventy-six patients were included in this study. The all-cause mortality was 13% (n = 10), with mean survival of 92.6 months. Among the patients, 9.2% (n = 7) had post-op renal failure requiring renal replacement therapy and 6.6% (n = 5) had post-op respiratory failure requiring intubation. Univariate analysis demonstrated that pre-operative left ventricular ejection fraction (LVEF), peak systolic tissue velocity at the tricuspid annulus (S') and etiology of MV disease were associated with respiratory and renal failure. Tricuspid annular plane systolic excursion (TAPSE) was associated with respiratory failure only. S', type of operation, LVEF, urgency of surgery, and etiology of MV disease were found to be predictive of mortality. After excluding redo mitral surgery, all statistically significant findings remain unchanged, with the addition of right ventricular (RV) size being associated with respiratory failure. In the subgroup analysis of routine cases (n = 56), patients with primary mitral regurgitation who underwent mitral valve repair had better survival outcome. Conclusions: Urgency of surgery, etiology of MV disease, type of operation (replacement or repair), S' and pre-op LVEF are prognostic indicators in this small cohort of patients with PH undergoing MV and TV surgery. A larger prospective study is warranted to validate our findings.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

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.

Hybrid trans-apical atrioventricular valve-in-valve implantation in Fontan circulation.

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.

Modified Single-Puncture Technique for Transcatheter Aortic Valve Implantation in Patients without Peripheral Vascular Access.

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.

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism.

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.

Comparison between D901 Lilliput 1 and Kids D100 neonatal oxygenators: toward bypass circuit miniaturization.

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.

Effects of angiotensin II type 1 receptor antagonist and temperature on prolonged cardioplegic arrest in neonatal rat myocytes.

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 modulation of apoptosis after ischemia and reperfusion. Angiotensin 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 perfusion 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: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic 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 delivery 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-1ß (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants.

Conventional aortic root vs valve-sparing root replacement surgery in aortic dilatation syndromes: a comparison of mortality and postoperative complications.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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 remodeling technique and aortic cusp repair in select patients, may impact in short-term procedural and long-term clinical success with valve-sparing surgery.

Surgical management of the aortic arch in patients with inherited aortopathy.

Surgical management of the aortic root and ascending aorta has seen an evolution over the past 50 years. Despite the widely available guidelines for management of the aortic root and ascending aorta, including in those with connective tissue disease and inherited aortopathies, there are generally no clear guideline indications for when to intervene on the aortic arch in these patients. This perhaps may be related to the fact that whilst the majority of acquired aortopathies, and also in non-syndromic aortopathies such as in bicuspid aortic valve, size criteria are utilized to decide on when to intervene, the use of size criteria may not be appropriate in those with syndromic inherited aortopathies. The aim of the present mini review is to provide a general overview and guidance for the surgical management of patients with inherited aortopathies.

Improving outcomes of surgery in advanced infiltrative thymic tumours: the benefits of multidisciplinary approach.

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.

Complete Surgical Resection of a Giant Invasive Thymoma with Right Pneumonectomy and Graft Reconstruction of the Superior Vena Cava and Left Brachiocephalic Vein: A Case Report.

Background: Complete surgical resection represents one of the most important prognostic factors for thymomas. However, surgery is usually not considered when there is invasion of the pulmonary hilum and mediastinal veins because of technical considerations or potential perioperative morbidity and mortality. Case Presentation. We present the case of a 37-year-old woman with a giant thymoma infiltrating the superior vena cava, left brachiocephalic vein, and most of the right lung. Following 3 cycles of chemotherapy with minimal tumour response, she was hospitalised with COVID-19 and refused further systemic treatment. She subsequently underwent surgery after a thorough preoperative evaluation. Surgical resection of the tumour was performed with concomitant right pneumonectomy and reconstruction of the superior vena cava and left brachiocephalic vein using expanded-polytetrafluoroethylene grafts through a median sternotomy combined with a clamshell incision. Histopathological analysis of the resected specimens demonstrated a type B2, Masaoka-Koga stage IVa thymoma that was completely resected. Following an uneventful course, she was discharged home on the ninth postoperative day with anticoagulation therapy. She has remained free of disease or adverse events after a 12-month follow-up. Conclusions: Complete surgical resection of invasive thymomas with concomitant pneumonectomy and venous graft reconstruction is a feasible and safe procedure. Careful patient selection and adequate postoperative anticoagulation are crucial for successful clinical outcomes.

Anatomy of a Transcatheter Mitral Valve Service.

Transcatheter mitral therapies offer treatment options to selected patients who are unable to undergo open procedures due to prohibitive surgical risk. Data detailing the design and structure of transcatheter mitral services to ensure appropriate patient selection and tailored management strategies is lacking. We report our initial experience of developing and running a purpose-built transcatheter mitral service. The nature and number of referral sources, the multi-disciplinary make-up of the dedicated Mitral Heart Team and the use of integrative imaging assessment with incorporation of computational solutions are discussed. In addition, a summary of the clinical decision-making process is presented. This report sets out a framework from which future clinics can evolve to improve and streamline the delivery of transcatheter mitral therapies.

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients. This review focuses on the prognosis of, preoperative planning for, and management strategies for patients with MAC.

Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

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 <2.0 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 weight <3.0 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.

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

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 mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1ß (-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 inflammatory 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.

Simulation and Measurement of Aerosolisation in Different Chest Drainage Systems.

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.

Multimodality Imaging in Transcatheter Mitral Interventions.

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.

Coagulation derangement and risk factors for valve thrombosis following transcatheter aortic valve implantation.

AIMS: Durability 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 RESULTS: This 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-TAVI CONCLUSION: This 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.

Ten-year improved survival in patients with multi-vessel coronary disease and poor left ventricular function following surgery: A retrospective cohort study.

OBJECTIVE: 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. METHODS: We retrospectively reviewed our data for 321 patients with EF < 30% 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. RESULTS: 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). CONCLUSION: 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.

Impaired angiotensin II-extracellular signal-regulated kinase signaling in failing human ventricular myocytes.

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.