Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

Fetal Doppler monitoring during maternal open-heart surgery: Case report and key aspects of a multidisciplinary challenge.

CASE REPORT: Herein we present the case of a 33-year nulliparous woman at 21 weeks of gestation with mitral valve vegetation resulting from infective endocarditis. Due to the mother's critical condition caused by consecutive thromboembolic events, surgery with cardiopulmonary bypass was indicated. During surgery the fetus was monitored by a specialized obstetrician who repetitively measured the Doppler indices of the umbilical artery, Ductus venosus and uterine artery. Right after CO2 was insufflated into the operating area, the Doppler monitoring showed an increased Pulsatility Index of the Umbilical artery right before fetal distress with bradycardia occurred. A subsequent maternal arterial blood gas analysis showed an acidosis with hypercapnia. Consequently, the CO2 insufflation was stopped and the gas flow on the Heart Lung Machine increased. After regaining homeostasis of acidosis, the Doppler Indices and fetal heart rate recovered. The remaining surgery and postoperative course were uneventful. At the 37 weeks of gestation a healthy boy was delivered by Cesarean section and at the age of two years, the neurodevelopment was assessed, which indicated normal development in mental cognition, language and motoric. This report presents a periodic Doppler examination of the maternal and fetal circulation during surgery on CPB while also discussing the possible impact of fetal monitoring in managing open cardiac surgery in pregnancy.

Manufacturing flexible vascular models for cardiovascular surgery planning and endovascular procedure simulations: An approach to segmentation and post-processing with open-source software and end-user 3D printers.

306Three-dimensional (3D)-printed vascular models for cardiovascular surgery planning and endovascular procedure simulations often lack realistic biological tissues mimicking material properties, including flexibility or transparency, or both. Transparent silicone or silicone-like vascular models were not available for end-user 3D printers and had to be fabricated using complex and cost-intensive workarounds. This limitation has now been overcome by novel liquid resins with biological tissue properties. These new materials enable simple and low-cost fabrication of transparent and flexible vascular models using end-user stereolithography 3D printers and are promising technological advances toward more realistic patient-specific, radiation-free procedure simulations and planning in cardiovascular surgery and interventional radiology. This paper presents our patient-specific manufacturing process of fabricating transparent and flexible vascular models using freely available open-source software for segmentation and 3D post-processing, aiming to facilitate the integration of 3D printing into clinical care.

Comparison of bicuspidization and Ross procedure in the treatment of unicuspid aortic valve disease in adults - Insight from the AVIATOR registry.

Background: Unicuspid aortic valve (UAV) is the second most common underlying cause of aortic valve dysfunction in young adults after the bicuspid valve. The valve may be replaced (for example by pulmonary autograft) or repaired using the bicuspidization technique. The aim of our study was to compare short- and mid-term outcomes of Ross procedure with bicuspidization in patients with severe UAV dysfunction. Methods: This was a multi-center retrospective observational cohort study comparing data from two dedicated Ross centers in the Czech Republic with bicuspidization outcomes provided by AVIATOR registry. As for the Ross group, only the patients with UAV were included. Primary endpoint was mid-term freedom from reintervention. Secondary endpoints were mid-term freedom from major adverse events, endocarditis and pacemaker implantation. Results: Throughout the study period, 114 patients underwent the Ross procedure (years 2009-2020) and 126 patients underwent bicuspidization (years 2006-2019). The bicuspidization group was significantly younger and presented with a higher degree of dyspnea, a lower degree of aortic valve stenosis and more often with pure regurgitation. The primary endpoint occurred more frequently in the bicuspidization group than in the Ross group - 77.9 vs. 97.9 % at 5 years and 68.4 vs. 75.2 % at 10 years (p < 0.001). There was no difference in secondary endpoints. Conclusion: Ross procedure might offer a significantly lower mid-term risk of reintervention than bicuspidization in patients with UAV. Both procedures have comparable survival and risk of other short- and mid-term complications postoperatively.

Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function.

We have recently shown that minor subclinical creatinine dynamic changes enable the excellent detection of acute kidney injury (AKI) within 6-12 h after cardiac surgery. The aim of the present study was to examine a combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine were determined after the induction of general anesthesia, at the termination of the cardiopulmonary bypass and 2 h thereafter. Out of 119 enrolled patients, 51 (43%) developed AKI. A model utilizing an NGAL, CysC and creatinine triple biomarker panel including sequential relative changes provides a better prediction of cardiac surgery-associated acute kidney injury than any biomarker alone already 2 h after the termination of the cardiopulmonary bypass. The area under the receiver-operator curve was 0.77, sensitivity 77% and specificity 68%.

Depth of cervical plexus block and phrenic nerve blockade: a randomized trial.

BACKGROUND AND OBJECTIVES: Cervical plexus blocks are commonly used to facilitate carotid endarterectomy (CEA) in the awake patient. These blocks can be divided into superficial, intermediate, and deep blocks by their relation to the fasciae of the neck. We hypothesized that the depth of block would have a significant impact on phrenic nerve blockade and consequently hemi-diaphragmatic motion. METHODS: We enrolled 45 patients in an observer blinded randomized controlled trial, scheduled for elective, awake CEA. Patients received either deep, intermediate, or superficial cervical plexus blocks, using 20 mL of 0.5% ropivacaine mixed with an MRI contrast agent. Before and after placement of the block, transabdominal ultrasound measurements of diaphragmatic movement were performed. Patients underwent MRI of the neck to evaluate spread of the injectate, as well as lung function measurements. The primary outcome was ipsilateral difference of hemi-diaphragmatic motion during forced inspiration between study groups. RESULTS: Postoperatively, forced inspiration movement of the ipsilateral diaphragm (4.34±1.06, 3.86±1.24, 2.04±1.20 (mean in cm±SD for superficial, intermediate and deep, respectively)) was statistically different between block groups (p<0.001). Differences were also seen during normal inspiration. Lung function, oxygen saturation, complication rates, and patient satisfaction did not differ. MRI studies indicated pronounced permeation across the superficial fascia, but nevertheless easily distinguishable spread of injectate within the targeted compartments. CONCLUSIONS: We studied the characteristics and side effects of cervical plexus blocks by depth of injection. Diaphragmatic dysfunction was most pronounced in the deep cervical plexus block group. TRIAL REGISTRATION NUMBER: EudraCT 2017-001300-30.

Aortic Root Pressurizing Device: Aortic Valve Evaluation During Cardioplegic Arrest.

PURPOSE: The aortic root pressurizing device was developed for aortic valve repair surgery. It allows echocardiographic evaluation of the aortic valve during cardioplegic arrest by mimicking diastolic afterload. DESCRIPTION: This polyoxymethylene or polyether ether ketone-based device consists of a sealing cap nut, a sealing ring, a plug screw, and both a filling and a ventilation line. It can be easily connected to any size of aortic Dacron grafts. EVALUATION: The device was tested in 15 porcine hearts using a beating heart biosimulator including hemodynamic and echocardiographic monitoring. Valve competence was analyzed on both the beating and resting heart at 60 and 45 mm Hg root pressure. Aortic insufficiency was surgically induced by leaflet manipulation. Native aortic valves showed either none or trivial aortic insufficiency. After leaflet manipulation echocardiographic proof of valve insufficiency was possible in all specimen. Jet direction was identic in all cases at 60 mm Hg and 93% at 45 mm Hg root pressure. CONCLUSIONS: The aortic root pressurizing device shows highly comparable results of echocardiographic aortic valve evaluation between static and dynamic settings under experimental conditions.

Successful long-term antibiotic suppressive therapy in a case of prosthetic valve endocarditis and a case of extensive aortic and subclavian graft infection.

INTRODUCTION: The indication for surgical valve replacement in cases of infective endocarditis is well defined in current guidelines. However, some patients are not fit or willing to undergo major surgical procedures. Interestingly, to the best of our knowledge, there is scarce information in the literature on how to deal with such cases and what might be the outcome. CASE REPORT: We present two complicated cases of prosthetic infective endocarditis with definite indication for replacement of involved foreign material, who were treated successfully with long-term suppressive antibiotic therapy. CONCLUSION: These two cases demonstrate that individualized long-term antibiotic suppressive therapy might be effective in selected patients with complicated PVE unfit or unwilling to undergo high-risk cardiothoracic surgical interventions.

Comparison of the conventional frozen elephant trunk implantation technique with a modified implantation technique in zone 1.

OBJECTIVES: The aim of the study was to compare the conventional frozen elephant trunk implantation technique with a modified implantation technique with an aortic anastomosis in zone 1 and extra-anatomic revascularization of the left subclavian artery during reperfusion. METHODS: Between May 2014 and March 2018, 40 patients (26 male; mean age 60.2 ± 11.2 years) underwent complete aortic arch replacement with the Thoraflex Hybrid prosthesis™ (Vascutek, Inchinnan, Scotland) at our institution. Seventeen patients underwent conventional arch replacement (group 1) and 23 patients the modified procedure (group 2). Indication for arch replacement included all types of acute and chronic diseases. RESULTS: Cardiopulmonary bypass time (213.1 ± 53.5 vs 243.8 ± 67.0 min, P = 0.13) and aortic cross-clamp time (114.4 ± 40.7 vs 117.3 ± 56.6 min, P = 0.86) did not differ significantly between group 1 and 2. There was a trend towards a shorter circulatory arrest time (50.72 ± 9.6 vs 44.7 ± 15.5 min; P = 0.20) in group 2. Perioperative mortality was 10% (5.9% vs 13%; P = 0.62). Stroke occurred in 10% (5.9% vs 13%; P = 0.62) of patients. Spinal cord injury occurred in 7.5% of patients (11.8% vs 4.3% P = 0.57). Due to the a proximal aortic anastomosis, there was a significantly shorter coverage of the descending aorta with the prosthesis ending at vertebral level Th7.5 (6.75-8) in group 1 versus Th6.0 (5.0-6.0) in group 2 (P-value = 0.004). CONCLUSIONS: Implantation of the frozen elephant trunk prosthesis in zone 1 allows for a more proximal aortic anastomosis that could make the procedure more feasible especially in patients with difficult anatomies or in an acute setting.

Evidence-based Surgery of Aortic Regurgitation: Results of a Questionnaire in German-speaking Countries.

BACKGROUND: evidence-based medicine (EBM) approaches have reached broad acceptance, both in conservative and surgical disciplines. The aim of this study is to clarify the role of EBM in a rare condition of aortic regurgitation (AR) with surgical indication. METHODS: A purpose-built Internet-based questionnaire was sent to 607 cardiovascular surgeons in Germany, Austria, and Switzerland. A virtual 64-year-old patient's medical history was presented, including two ultrasound images and one computed tomography scan, showing a 58-mm aortic root aneurysm and a severe trileaflet regurgitant aortic valve. Participants had to choose their preferred therapeutic strategy from a list. Additionally, demographics including nationality, the center size, and the frequency of similar types of patients referred to their departments were collected. RESULTS: Of 607 questionnaires, 100 were returned (16%). One participant was excluded due to conflicting answers. Most surgeons (n = 84; 84%) chose a valve-sparing root replacement (VSRR). A Bentall procedure was preferred by 13 surgeons (13%). Two surgeons voted for aortic valve replacement combined with partial root resection. The decision-making process was not significantly influenced by center size, nationality, or frequency of patients. CONCLUSION: Applying the current guidelines to our virtual study patient, 84% of participants acted accordingly choosing VSRR. Remarkably, 14% of these surgeons see less than 10 and 43% see not more than 20 comparable patients per year. Since the guidelines reserve VSRR for competent centers, those numbers as well as the guidelines themselves should be further discussed.

Clinical experience with the freedom SOLO stentless aortic valve in 277 consecutive patients.

BACKGROUND: The Sorin Freedom SOLO (FS) bovine pericardial stentless valve prosthesis is designed for supraannular, subcoronary implantation. We report our experience and results with 277 consecutively implanted FS bioprostheses. METHODS: 277 patients (mean age, 74.2 ± 7.3 years; 139 (50.2%) female) underwent aortic valve replacement (AVR) with the FS stentless bioprosthesis. The hemodynamic performance was investigated with transthoracic echocardiography at discharge, 6 months later, and yearly thereafter. Follow-up was 100% complete, with an average observation time of 2.6 ± 1.7 years and a total of 697.3 patient-years. RESULTS: The overall 30-day mortality was 4.3%. The mortalities for isolated AVR and combined procedures were 1.9% and 7.3%, respectively. No causes of death were valve-related. Preoperative peak (74.2 ± 23.0 mm Hg) and mean (48.6 ± 16.3 mm Hg) gradients decreased to 15.6 ± 5.4 mm Hg and 8.8 ± 3.0 mm Hg postoperatively and remained unchanged for as long as 5 years. The postoperative mean effective orifice area (EOA) for valve sizes 19, 21, 23, 25, and 27 were 1.49 ± 0.32 cm(2), 1.67 ± 0.40 cm(2), 1.92 ± 0.38 cm(2), 2.01 ± 0.42 cm(2), and 2.13 ± 0.36 cm(2), respectively. Severe prosthesis-patient mismach (PPM) was completely absent, and moderate PPM occurred in 17 patients (6.1%). In isolated AVR, 0.8% of patients with preoperative sinus rhythm required a permanent pacemaker before hospital discharge. There was 100% freedom from structural valve deterioration, 99.6 % freedom from endocarditis and reoperation, and 97.3% freedom from thromboembolism at 5 years. CONCLUSIONS: The FS stentless aortic valve is safe to implant, and it shows excellent hemodynamic performance and early and midterm results. Owing to the favorable EOA, the valve appears particularly attractive for patients at risk for PPM.

Retroesophageal right subclavian artery (lusoria) as origin of traumatic aortic rupture.

A retroesophageal right subclavian artery (lusoria) is unusual for the surgeon, yet common regarding pathological findings (0.5-2%). Complications arising from it are rare (dysphagia). We report a case of traumatic descending aortic tear originating from a lusoria. The patient had experienced chest trauma due to a skiing accident. CT scan revealed an intramural haematoma of the proximal descending aorta. As a coincidence finding, a retroesophageal right subclavian artery was diagnosed. The patient was first treated conservatively. After an initial period--of stable patient conditions--repeated CT scan revealed a haematoma enlargement and surgery was scheduled: A localized aortic tear was suspected through CT scan, yet no aortic tear or flap was visible. During a two-staged surgical procedure, transpositioning of the lusoria into the right common carotid artery was performed, followed by replacement of the distal aortic arch during a second session using a single-branched Dacron tube graft. The left subclavian artery was then reinserted into the side-branched graft after reuptake of extracorporeal circulation. Extracorporeal circulation was applied via the femoral vessels and circulatory arrest in combination with deep hypothermia. After surgery, the patient was stable, having no signs of neurocognitive dysfunction or dysphagia.