How to counteract the lack of donor tissue in cardiac surgery? Initial experiences with a newly established homograft procurement program.

Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support.

Stenting of native right ventricular outflow tract obstructions in symptomatic infants: histological work-up of explanted specimen.

BACKGROUND: Stenting of stenotic right ventricular outflow tract is a palliative measure for severely impaired small babies with Tetralogy of Fallot or similar pathologies. Little is known about the histopathological fate of the stents in the right ventricular outflow tract. METHODS: Eight samples of surgically removed right ventricular outflow tract stents were histologically analysed according to a predefined protocol. RESULTS: The most frequent diagnosis was Tetralogy of Fallot in four patients, pulmonary atresia with ventricular septal defect in two patients, double outlet right ventricle with pulmonary obstruction in one patient, and muscular obstruction of the right ventricular outflow tract in one patient with a syndromic disease with hypertrophic cardiomyopathy. Stents mean implantation duration was 444 days ranging from 105 to 1117 days (median 305.5 days). Histology revealed a variable degree of pseudointima formation consisting of fibromuscular cells surrounded by extracellular matrix. Four of the specimen contained adjacent myocardial tissue fragments, which showed regressive changes. Neither myocardium nor pseudointima tissue or tissue parts locally related to stent struts were infiltrated by inflammatory cells. CONCLUSIONS: Histological analysis after explantation of early-in-life implanted right ventricular outflow tract stents revealed predominantly pronounced neo-intimal proliferation with a visible endothelial layer, no signs of inflammation, and no prolapse of muscular tissue through the stent struts. Thus, implantation of stents in early life seems to interfere little with the hosts' immune system and might help to open up the right ventricular outflow tract by mechanical forces and regressive changes in adjacent muscular tissue.

Chronic SIRT1 supplementation in diabetic mice improves endothelial function by suppressing oxidative stress.

AIMS: Enhancing SIRT1 activity exerts beneficial cardiovascular effects. In diabetes, plasma SIRT1 levels are reduced. We aimed to investigate the therapeutic potential of chronic recombinant murine SIRT1 (rmSIRT1) supplementation to alleviate endothelial and vascular dysfunction in diabetic mice (db/db). METHODS AND RESULTS: Left internal mammary arteries obtained from patients undergoing coronary artery bypass grafting with or without a diagnosis of diabetes were assayed for SIRT1 protein levels. Twelve-week-old male db/db mice and db/+ controls were treated with vehicle or rmSIRT1 intraperitoneally for 4 weeks, after which carotid artery pulse wave velocity (PWV) and energy expenditure/activity were assessed by ultrasound and metabolic cages, respectively. Aorta, carotid, and mesenteric arteries were isolated to determine endothelial and vascular function using the myograph system.Arteries obtained from diabetic patients had significantly lower levels of SIRT1 relative to non-diabetics. In line, aortic SIRT1 levels were reduced in db/db mice compared to db/+ mice, while rmSIRT1 supplementation restored SIRT1 levels. Mice receiving rmSIRT1 supplementation displayed increased physical activity and improved vascular compliance as reflected by reduced PWV and attenuated collagen deposition. Aorta of rmSIRT1-treated mice exhibited increased endothelial nitric oxide (eNOS) activity, while endothelium-dependent contractions of their carotid arteries were significantly decreased, with mesenteric resistance arteries showing preserved hyperpolarization. Ex vivo incubation with reactive oxygen species (ROS) scavenger Tiron and NADPH oxidase inhibitor apocynin revealed that rmSIRT1 leads to preserved vascular function by suppressing NADPH oxidase (NOX)-related ROS synthesis. Chronic rmSIRT1 treatment resulted in reduced expression of both NOX1 and NOX4, in line with a reduction in aortic protein carbonylation and plasma nitrotyrosine levels. CONCLUSIONS: In diabetic conditions, arterial SIRT1 levels are significantly reduced. Chronic rmSIRT1 supplementation improves endothelial function and vascular compliance by enhancing eNOS activity and suppressing NOX-related oxidative stress. Thus, SIRT1 supplementation may represent novel therapeutic strategy to prevent diabetic vascular disease.

Twenty-five year experience with aortic valve-sparing root replacement in a single teaching center.

Objectives: Aortic valve-sparing root replacement (AVSRR) is a technically demanding procedure. In experienced centers it offers excellent short- and long-term results, making the procedure an attractive alternative for aortic root replacement especially in young patients. The aim of this study was to analyze long-term results of AVSRR using the David operation in our institution over the last 25 years. Methods: This is a single-center retrospective analysis of outcomes of David operations performed in a teaching institution not running a large AVSRR-program. Pre-, intra- and postoperative data were collected from the institutional electronic medical record system. Follow-up data were collected through direct contact of the patients and their cardiologists/primary care physicians. Results: Between 02/1996 and 11/2019, 131 patients underwent David operation in our institution by a total of 17 different surgeons. Median age was 48 (33-59), 18% were female. Elective surgery was performed in 89% of the cases, 11% were operated as emergency in the setting of an acute aortic dissection. Connective tissue disease was present in 24% and 26% had a bicuspid aortic valve. At hospital admission 61% had aortic regurgitation grade ≥3, 12% were in functional NYHA-class ≥III. 30-day mortality was 2%, 97% of the patients were discharged with aortic regurgitation ≤2. In 10-year follow-up, 15 (12%) patients had to be re-operated because of root-related complications. Seven patients (47%) received a transcatheter aortic valve implantation, 8 (53%) required surgical replacement of the aortic valve or a Bentall-De Bono operation. Estimated reoperation-free survival at 5 and 10 years was 93.5% ± 2.4% and 87.0% ± 3.5%, respectively. Subgroup analysis showed no differences in reoperation-free survival for patients presenting with a bicuspid valve or preoperative aortic regurgitation ≥3. However a preoperative left ventricular end diastolic diameter of ≥5.5 cm was associated with worse outcome. Conclusion: David operations can be performed with excellent perioperative and 10-year follow-up outcomes in centers not running large AVSRR-programs.

Long-distance donor heart procurement using an innovative cold static storage system.

The global lack of donor shortage poses a major limitation for heart transplantation. New concepts with expanded donor inclusion criteria comprise extended transport distances and prolonged ischemic times with the aim of reaching a larger number of potential donors. Recent developments in cold storage solutions may allow more donor hearts with prolonged ischemic times to be use for transplantation in the future. We present our experience during a long-distance donor heart procurement with the longest reported transport distance and transport time in the current literature. This was made possible through the use of SherpaPak™, an innovative cold storage system which allows for controlled temperatures during transportation.

Anomalous Origin of Left Circumflex Coronary Artery From Right Pulmonary Artery: An Unusual Cause of Sudden Cardiac Arrest.

Anomalous origin of the left circumflex coronary artery from the right pulmonary artery is an extremely rare coronary anomaly out of the group of anomalous coronary arteries arising from the pulmonary artery. We present the case of a 27-year-old male, in whom the diagnosis of an anomalous left circumflex coronary artery from the pulmonary artery was made after sudden cardiac arrest. The diagnosis was confirmed by multimodal imaging and the patient underwent successful surgical correction. Abnormal origins of a coronary artery may become symptomatic later in life and may occur as an isolated cardiac malformation. Due to a potentially unfavorable clinical course, surgical correction should be considered as soon as a diagnosis is made.

Intracardiac bone cement embolism resulting in ventricular perforation: an unusual cause of sudden chest pain.

Leakage of bone cement is a known complication after percutaneous kyphoplasty. In rare cases, bone cement can reach the venous system and cause life-threatening embolism. We present the case of a 73-year-old male, who was admitted to our hospital with new-onset chest pain and dyspnoea. He had a history of percutaneous kyphoplasty. Multimodal imaging showed intracardiac cement embolism in the right ventricle with penetration of the interventricular septum and perforation of the apex. The bone cement was successfully removed during open cardiac surgery.

MitraClip® procedure as bridge to left ventricular assist device: Enable extracorporeal membrane oxygenation weaning and reduce perioperative risk.

Secondary mitral valve regurgitation is a frequent consequence of left ventricular dysfunction in patients with severe heart failure. The management of this disease can be challenging since it often culminates in refractory pulmonary edema and multi-organ failure. We present the case of a 50-year-old male who was admitted in cardiogenic shock following myocardial infarction. After successful revascularization, percutaneous mitral valve repair using the MitraClip® device enabled weaning from extracorporeal membrane oxygenation followed by the implantation of a left ventricular assist device as bridge to transplant.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes.

AIMS: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44-10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19-3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04-3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62-19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19-5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: -4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59-0.86; P = 0.0031). CONCLUSION: Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. CLINICAL TRIAL REGISTRATION: NCT01000701.

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection.

OBJECTIVES: Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD). METHODS: This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation. RESULTS: Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99). CONCLUSIONS: Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.

Routine early postoperative computed tomography angiography after coronary artery bypass surgery: clinical value and management implications.

OBJECTIVES: Computed tomography angiography (CTA) is broadly used for long-term follow-up of graft patency after coronary artery bypass graft surgery (CABG). However, its clinical value in the early postoperative setting has not been established yet. We evaluated the benefit of adding CTA to the routine clinical work-up after CABG on patient management. METHODS: A total of 305 consecutive patients (269 males, median age 68 years) underwent CABG and postoperative CTA with a median of 6 days after surgery. Graft patency and additional imaging findings were assessed and their influence on diagnosis and clinical management was evaluated. RESULTS: Graft occlusion or high-grade stenosis was found in 15% of the patients. Additional findings were reported in 44% of the patients, including pericardial (2%) and pleural effusion (27%), large pneumothorax (11%), pulmonary infection (4%), cardiac or vascular thrombus (2%), pulmonary embolism (2%), sternal dehiscence (1%) and additional incidental findings requiring follow-up (6%). CT findings initiated new diagnostic and/or therapeutic measures in 15% of the patients, 47% of those with diseased grafts and 19% of patients with non-graft-related findings. No adverse events related to CTA were documented. CONCLUSIONS: Early routine postoperative assessment of CABG with CTA reveals both cardiac and non-cardiac findings with a high frequency, affecting clinical management in a substantial proportion of patients.

What does an explanted PASCAL device look like?

We report the case of a 78-year-old female patient who had a PASCAL device implanted for severe degenerative mitral regurgitation. Intraprocedural echocardiography revealed persistent severe mitral regurgitation due to device dislocation. Implanting another device was not possible. After 8 days, the device was explanted, and the valve was replaced with a biological prosthesis. The PASCAL device and resected mitral valve leaflets were sent for histopathological workup.

Transcatheter mitral valve repair using the Cardioband® system: Histopathological insights in device ingrowth and biocompatibility.

Surgical implantation of a complete or incomplete ring to reduce the valve annulus and improve leaflet coaptation is the mainstay of mitral valve surgery. The Cardioband® system (Edwards Lifesciences) was designed to address the pathophysiological mechanism of annular dilatation through a catheter-based approach. We present the histopathological workup of a Cardioband® device, which had been implanted 21 months earlier in a 34-year-old male with ischemic cardiomyopathy. Device examination demonstrate a well-positioned and securely anchored device. The described tissue reactions may have an impact on choice of device and timing in case of re-do surgery.

Resilience of the Internal Mammary Artery to Atherogenesis: Shifting From Risk to Resistance to Address Unmet Needs.

Fueled by the global surge in aging, atherosclerotic cardiovascular disease reached pandemic dimensions putting affected individuals at enhanced risk of myocardial infarction, stroke, and premature death. Atherosclerosis is a systemic disease driven by a wide spectrum of factors, including cholesterol, pressure, and disturbed flow. Although all arterial beds encounter a similar atherogenic milieu, the development of atheromatous lesions occurs discontinuously across the vascular system. Indeed, the internal mammary artery possesses unique biological properties that confer protection to intimal growth and atherosclerotic plaque formation, thus making it a conduit of choice for coronary artery bypass grafting. Its endothelium abundantly expresses nitric oxide synthase and shows accentuated nitric oxide release, while its vascular smooth muscle cells exhibit reduced tissue factor expression, high tPA (tissue-type plasminogen activator) production and blunted migration and proliferation, which may collectively mitigate intimal thickening and ultimately the evolution of atheromatous plaques. We aim here to provide insights into the anatomy, physiology, cellular, and molecular aspects of the internal mammary artery thereby elucidating its remarkable resistance to atherogenesis. We propose a change in perspective from risk to resilience to decipher mechanisms of atheroresistance and eventually identification of novel therapeutic targets presently not addressed by currently available remedies.

Initiation of an inter-hospital extracorporeal membrane oxygenation transfer programme for critically ill patients with coronavirus disease 2019: bringing extracorporeal membrane oxygenation support to peripheral hospitals.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a resource-intensive, highly specialized and expensive therapy that is often reserved for high-volume centres. In recent years, we established an inter-hospital ECMO transfer programme that enables ECMO implants in peripheral hospitals. During the pandemic, the programme was expanded to include ECMO support in selected critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective single-centre study reports the technical details and challenges encountered during our initial experience with ECMO implants in peripheral hospitals for patients with COVID-19. RESULTS: During March and April 2020, our team at the University Hospital of Zurich performed 3 out-of-centre ECMO implants at different peripheral hospitals. The implants were performed without any complications. The patients were transported by ambulance or helicopter. Good preparation and selection of the required supplies are the keys to success. The implant should be performed by a well-trained, seasoned ECMO team, because options are limited in most peripheral hospitals. CONCLUSIONS: Out-of-centre ECMO implants in well-selected patients with COVID-19 is feasible and safe if a well-established organization is available and if the implantation is done by an experienced and regularly trained team.

An innovative cold storage system for donor heart transportation-lessons learned from the first experience in Switzerland.

BACKGROUND: The current standard for donor heart preservation consists of cold organ storage in three sequential plastic bags. This technique can cause freezing injuries of the donor heart as the temperature inside the transport box is not monitored routinely. The SherpaPak™ Cardiac Transport System (CTS) (Paragonix Technologies, Cambridge, MA, USA) aims to resolve this problem by maintaining a controlled preservation temperature between 4 and 8 °C. This study reports the first single-centre experience in Switzerland with this innovative single-use disposable device. METHODS: Between May and December 2020, four heart procurements using SherpaPak™ CTS were performed at our heart centre. Donor heart preservation fluid and ambient temperature were monitored using the InTempConnect® application (Onset Computer Corporation, Bourne, MA, USA). All patient data were collected retrospectively from the local hospital patient data capture system. RESULTS: Four recipients of a donor heart preserved with SherpaPak™ CTS were included in this study (3 male, 1 female). Mean transport distance was 86 km (range, 45-276 km). Mean storage time in the cooler was 73.5±19.33 minutes. Mean cold ischemic time was 199.25±11.67 minutes. The device kept the average organ temperature between 5.2 and 8.8 °C and hereby reached the recommended temperature range of 5-10 °C. Modifications of the procurement and storage process provided an optimization of the temperature course in the transportation box. There were no incidents during the transport. Organs transported with this novel storage system showed normal function after transplantation. CONCLUSIONS: The SherpaPak™ CTS provides constant organ temperatures during transportation, prevents freezing injury and ensures mechanical protection of the graft. KEYWORDS: Heart transplantation; organ procurement; cold storage; hypothermic injury; graft transport.