Antithrombotic therapy after heart valve surgery, contemporary practice in the United Kingdom.

OBJECTIVES: There is a lack of high-quality data informing the optimal antithrombotic drug strategy following bioprosthetic heart valve replacement or valve repair. Disparity in recommendations from international guidelines reflects this. This study aimed to document current patterns of antithrombotic prescribing after heart valve surgery in the UK. METHODS: All UK consultant cardiac surgeons were e-mailed a custom-designed survey. The use of oral anticoagulant (OAC) and/or antiplatelet drugs following bioprosthetic aortic (AVR) or mitral valve replacement (MVR), or mitral valve repair (MVrep), for patients in sinus rhythm, without additional indications for antithrombotic medication, was assessed. Additionally, we evaluated anticoagulant choice following MVrep in patients with atrial fibrillation (AF). RESULTS: We identified 260 UK consultant cardiac surgeons from 36 units, of whom 103 (40%) responded, with 33 units (92%) having at least one respondent. The greatest consensus was for patients undergoing bioprosthetic AVR, in which 76% of surgeons favour initial antiplatelet therapy and 53% prescribe lifelong treatment. Only 8% recommend initial OAC. After bioprosthetic MVR, 48% of surgeons use an initial OAC strategy (versus 42% antiplatelet), with 66% subsequently prescribing lifelong antiplatelet therapy. After MVrep, recommendations were lifelong antiplatelet agent alone (34%) or following 3 months OAC (20%), no antithrombotic agent (20%), or 3 months OAC (16%). After MVrep for patients with established AF, surgeons recommend warfarin (38%), a direct oral anticoagulant (37%) or have no preference between the two (25%). CONCLUSIONS: There is considerable variation in the use of antithrombotic drugs after heart valve surgery in the UK and a lack of high-quality evidence to guide practice, underscoring the need for randomized studies.

Comparison of storage solutions on saphenous vein endothelial function using immunofluorescence. A pilot study.

BACKGROUND: Our aim was to establish which of the current and novel storage fluids caused the least harm to the endothelium of the saphenous vein. METHODS: Unmanipulated samples of saphenous vein were obtained. This vein was exposed to four fluids, DuraGraft®, Plasma-Lyte, autologous blood and sodium chloride, and a control medium. The expression of endothelial selectin (E-selectin) and endothelial nitric oxide synthase (eNOS) was measured using confocal microscopy. RESULTS: We identified and quantified platelet endothelial cell adhesion molecules, vascular cell adhesion molecules and endothelial nitric oxide synthase 3 on the endothelium. The results were widely variable. The protein expression of endothelial selectin (p = .17) and endothelial nitric oxide synthase 3 (p = .73) showed no statistically significant differences in levels of preservation when the different solutions were compared. CONCLUSIONS: In this study, we could not determine that any of the solutions were superior at preserving saphenous vein endothelium.

Negative pressure wound therapy in patients with diabetes undergoing left internal thoracic artery harvest: A randomized control trial.

BACKGROUND: Patients with diabetes undergoing CABG are at risk of wound infection. Incisional negative pressure wound therapy has been shown to be effective in decreasing incidence of infection in high-risk wounds. Near infrared spectroscopy (NIRS) can be used to assess wound oxygenation and low values can predict infection. OBJECTIVES: To evaluate utility of NIRS to assess wound oxygenation, to assess effect of sternotomy, left internal thoracic artery harvest, and wound dressing type on wound edge oxygenation. METHODS: In this blinded randomized control trial, patients with diabetes undergoing isolated coronary artery bypass grafting with a left internal thoracic artery were randomized to receive either incisional negative pressure wound therapy dressing or a standard dressing. NIRS measurements were made on the left upper arm (control), and left and right parasternal regions on day -1 (preoperative), day 5, and week 6 after surgery. Results were analyzed using repeated measures parametric methods. RESULTS: Eighty patients with diabetes were recruited, 40 to the incisional negative pressure wound therapy group and 40 to the standard dressing group. Adjusted NIRS readings dropped significantly in all patients by day 5 and partially recovered by week 6. In both groups, there was no difference between readings on the left and right. At all time points and on both sides, there was no difference in readings between patients in the 2 groups. CONCLUSIONS: NIRS can be used to assess oxygenation adjacent to a sternotomy wound. Adjusted tissue oxygen levels change with time after sternotomy and left internal thoracic artery harvest in patients with diabetes. Wound dressing type does not influence day 5 wound edge oxygenation.

Antithrombotic therapy after heart valve intervention: review of mechanisms, evidence and current guidance.

As the population ages and treatment options for heart valve disease increase, the number of patients with intracardiac valve prostheses is growing rapidly. Although all devices have the potential to cause thrombus formation, the propensity depends on the type of prosthesis as well as risk of the individual patient. Mechanical valve prostheses carry the highest (and persistent) risk of thromboembolism, and these patients require anticoagulation with vitamin K antagonists (warfarin). Required international normalised ratio levels are dependent on the location of the valve (mitral>aortic), type of valve (ball and cage vs bilealfet vs On-X bilealfet) and rhythm. The risk of tissue (biological) prosthesis is highest soon after surgery and is dependent on individual patient risk including age, valve location (mitral>aortic), history of thromboembolic events and rhythm. In patients with no other indication for anticoagulation, there is uncertainty on the benefits of anticoagulation versus antiplatelet therapy in patients with tissue prostheses or repaired native valves. Patients with an a priori indication for anticoagulation with a direct oral anticoagulant can continue taking this class of drug. Patients with transcatheter aortic valve implantation devices and no additional evidence-based indication for dual antiplatelet therapy or anticoagulation can be maintained on aspirin monotherapy. Patients undergoing transcatheter instrumentation in the mitral valve position should be anticoagulated, although there is currently no published evidence for antithrombotic management in this group of patients. Patients with thrombosed devices (commonly mitral mechanical) should preferably be treated surgically. Patients at high risk of thromboembolism (with mechanical prostheses) should undergo bridging therapy when undergoing surgery.

Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.

BACKGROUND: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described. METHODS AND RESULTS: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions. CONCLUSION: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Portable ultrasound assessment of jugular venous pressure is an accurate method for estimating volaemic status in patients with cardiac disease.

PURPOSE: The objective of this study was to determine whether ultrasound-measured jugular venous pressure (U-JVP) could accurately estimate central venous pressure (CVP). METHODS: This prospective, diagnostic, single-centre study was performed at the Cardiac Intensive Care Unit of the Northern General Hospital, Sheffield, UK. Post-cardiac surgery patients were recruited from January to May 2019. The investigators were blinded to the central venous pressure when measuring the jugular venous pressure. U-JVP and direct CVP were measured simultaneously. Measurements were taken whilst the patient was ventilated and then repeated when the patient was extubated, providing non-ventilated readings. RESULTS: One-hundred and fourteen consecutive participants with a male predominance of 71% and mean age of 65 ± 12 years were included in the analysis. Bland-Altman plots revealed that U-JVP marginally overestimated CVP by 0.91 mmHg (95% limits of agreement were -2.936 to 4.754) in ventilated patients and by 0.11 mmHg (95% limits of agreement between -2.481 and 2.695) in non-ventilated patients. Reasonable sensitivity and specificity of ultrasound-measured jugular venous pressure was achieved for low and high central venous pressure in both ventilated and non-ventilated patients. CONCLUSION: U-JVP accurately estimates cardiac filling pressure and fluid status in patients after cardiac surgery, irrespective of their ventilatory status. Jugular venous pressure measurement by insonation is a reliable technique that can be taught to medical students and other health professionals to non-invasively estimate central venous pressure and may be useful for assessment of volaemic status in patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov public (identifier NCT03815188).

Surgical aortic valve replacement in the era of transcatheter aortic valve implantation: a review of the UK national database.

OBJECTIVES: To date the reported outcomes of surgical aortic valve replacement (SAVR) are mainly in the settings of trials comparing it with evolving transcatheter aortic valve implantation. We set out to examine characteristics and outcomes in people who underwent SAVR reflecting a national cohort and therefore 'real-world' practice. DESIGN: Retrospective analysis of prospectively collected data of consecutive people who underwent SAVR with or without coronary artery bypass graft (CABG) surgery between April 2013 and March 2018 in the UK. This included elective, urgent and emergency operations. Participants' demographics, preoperative risk factors, operative data, in-hospital mortality, postoperative complications and effect of the addition of CABG to SAVR were analysed. SETTING: 27 (90%) tertiary cardiac surgical centres in the UK submitted their data for analysis. PARTICIPANTS: 31 277 people with AVR were identified. 19 670 (62.9%) had only SAVR and 11 607 (37.1%) had AVR+CABG. RESULTS: In-hospital mortality for isolated SAVR was 1.9% (95% CI 1.6% to 2.1%) and was 2.4% for AVR+CABG. Mortality by age category for SAVR only were: <60 years=2.0%, 60-75 years=1.5%, >75 years=2.2%. For SAVR+CABG these were; 2.2%, 1.8% and 3.1%. For different categories of EuroSCORE, mortality for SAVR in low risk people was 1.3%, in intermediate risk 1% and for high risk 3.9%. 74.3% of the operations were elective, 24% urgent and 1.7% emergency/salvage. The incidences of resternotomy for bleeding and stroke were 3.9% and 1.1%, respectively. Multivariable analyses provided no evidence that concomitant CABG influenced outcome. However, urgency of the operation, poor ventricular function, higher EuroSCORE and longer cross clamp and cardiopulmonary bypass times adversely affected outcomes. CONCLUSIONS: Surgical SAVR±CABG has low mortality risk and a low level of complications in the UK in people of all ages and risk factors. These results should inform consideration of treatment options in people with aortic valve disease.

Left ventricular blood flow kinetic energy is associated with the six-minute walk test and left ventricular remodelling post valvular intervention in aortic stenosis.

BACKGROUND: Left ventricular (LV) kinetic energy (KE) assessment by four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) may offer incremental value over routine assessment in aortic stenosis (AS). The main objective of this study is to investigate the LV KE in patients with AS before and after the valve intervention. In addition, this study aimed to investigate if LV KE offers incremental value for its association to the six-minute walk test (6MWT) or LV remodelling post-intervention. METHODS: We recruited 18 patients with severe AS. All patients underwent transthoracic echocardiography for mean pressure gradient (mPG), CMR including 4D flow and 6MWT. Patients were invited for post-valve intervention follow-up CMR at 3 months and twelve patients returned for follow-up CMR. KE assessment of LV blood flow and the components (direct, delayed, retained and residual) were carried out for all cases. LV KE parameters were normalised to LV end-diastolic volume (LVEDV). RESULTS: For LV blood flow KE assessment, the metrics including time delay (TD) for peak E-wave from base to mid-ventricle (14±48 vs. 2.5±9.75 ms, P=0.04), direct (4.91±5.07 vs. 1.86±1.72 µJ, P=0.01) and delayed (2.46±3.13 vs. 1.38±1.15 µJ, P=0.03) components of LV blood flow demonstrated a significant change between pre- and post-valve intervention. Only LV KEiEDV (r=-0.53, P<0.01), diastolic KEiEDV (r=-0.53, P<0.01) and Ewave KEiEDV (r=-0.38, P=0.04) demonstrated association to the 6MWT. However, Pre-operative LV KEiEDV (r=0.67, P=0.02) demonstrated association to LV remodelling post valve intervention. CONCLUSIONS: LV blood flow KE is associated with 6MWT and LV remodelling in patients with AS. LV KE assessment provides incremental value over routine LV function and pressure gradient (PG) assessment in AS.

Standard and emerging CMR methods for mitral regurgitation quantification.

BACKGROUND: There are several methods to quantify mitral regurgitation (MR) by cardiovascular magnetic resonance (CMR). The interoperability of these methods and their reproducibility remains undetermined. OBJECTIVE: To determine the agreement and reproducibility of different MR quantification methods by CMR across all aetiologies. METHODS: Thirty-five patients with MR were recruited (primary MR = 12, secondary MR = 10 and MVR = 13). Patients underwent CMR, including cines and four-dimensional flow (4D flow). Four methods were evaluated: MRStandard (left ventricular stroke volume - aortic forward flow by phase contrast), MRLVRV (left ventricular stroke volume - right ventricular stroke volume), MRJet (direct jet quantification by 4D flow) and MRMVAV (mitral forward flow by 4D flow - aortic forward flow by 4D flow). For all cases and MR types, 520 MR volumes were recorded by these 4 methods for intra-/inter-observer tests. RESULTS: In primary MR, MRMVAV and MRLVRV were comparable to MRStandard (P > 0.05). MRJet resulted in significantly higher MR volumes when compared to MRStandard (P < 0.05) In secondary MR and MVR cases, all methods were comparable. In intra-observer tests, MRMVAV demonstrated least bias with best limits of agreement (bias = -0.1 ml, -8 ml to 7.8 ml, P = 0.9) and best concordance correlation coefficient (CCC = 0.96, P < 0.01). In inter-observer tests, for primary MR and MVR, least bias and highest CCC were observed for MRMVAV. For secondary MR, bias was lowest for MRJet (-0.1 ml, PNS). CONCLUSION: CMR methods of MR quantification demonstrate agreement in secondary MR and MVR. In primary MR, this was not observed. Across all types of MR, MRMVAV quantification demonstrated the highest reproducibility and consistency.

Outpatient management of heart valve disease following the COVID-19 pandemic: implications for present and future care.

The established processes for ensuring safe outpatient surveillance of patients with known heart valve disease (HVD), echocardiography for patients referred with new murmurs and timely delivery of surgical or transcatheter treatment for patients with severe disease have all been significantly impacted by the novel coronavirus pandemic. This has created a large backlog of work and upstaging of disease with consequent increases in risk and cost of treatment and potential for worse long-term outcomes. As countries emerge from lockdown but with COVID-19 endemic in society, precautions remain that restrict 'normal' practice. In this article, we propose a methodology for restructuring services for patients with HVD and provide recommendations pertaining to frequency of follow-up and use of echocardiography at present. It will be almost impossible to practice exactly as we did prior to the pandemic; thus, it is essential to prioritise patients with the greatest clinical need, such as those with symptomatic severe HVD. Local procedural waiting times will need to be considered, in addition to usual clinical characteristics in determining whether patients requiring intervention would be better suited having surgical or transcatheter treatment. We present guidance on the identification of stable patients with HVD that could have follow-up deferred safely and suggest certain patients that could be discharged from follow-up if waiting lists are triaged with appropriate clinical input. Finally, we propose that novel models of working enforced by the pandemic-such as increased use of virtual clinics-should be further developed and evaluated.

Validation of four-dimensional flow cardiovascular magnetic resonance for aortic stenosis assessment.

The management of patients with aortic stenosis (AS) crucially depends on accurate diagnosis. The main aim of this study were to validate the four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) methods for AS assessment. Eighteen patients with clinically severe AS were recruited. All patients had pre-valve intervention 6MWT, echocardiography and CMR with 4D flow. Of these, ten patients had a surgical valve replacement, and eight patients had successful transcatheter aortic valve implantation (TAVI). TAVI patients had invasive pressure gradient assessments. A repeat assessment was performed at 3-4 months to assess the remodelling response. The peak pressure gradient by 4D flow was comparable to an invasive pressure gradient (54 ± 26 mmHG vs 50 ± 34 mmHg, P = 0.67). However, Doppler yielded significantly higher pressure gradient compared to invasive assessment (61 ± 32 mmHG vs 50 ± 34 mmHg, P = 0.0002). 6MWT was associated with 4D flow CMR derived pressure gradient (r = -0.45, P = 0.01) and EOA (r = 0.54, P < 0.01) but only with Doppler EOA (r = 0.45, P = 0.01). Left ventricular mass regression was better associated with 4D flow derived pressure gradient change (r = 0.64, P = 0.04). 4D flow CMR offers an alternative method for non-invasive assessment of AS. In addition, 4D flow derived valve metrics have a superior association to prognostically relevant 6MWT and LV mass regression than echocardiography.

Offset of ticagrelor prior to coronary artery bypass graft surgery for acute coronary syndromes: effects on platelet function and cellular adenosine uptake.

Ticagrelor is an antagonist of both platelet adenosine diphosphate (ADP) receptor P2Y12 and equilibrative nucleoside transporter-1. Optimal timing of ticagrelor cessation prior to coronary artery bypass grafting (CABG) remains unclear. We characterized the offset of ticagrelor's effects on platelets and cellular adenosine uptake in ticagrelor-treated patients (n = 13) awaiting CABG. Blood was drawn prior to CABG at multiple timepoints 2 to 120 (h) after the last dose of ticagrelor. Platelet function (n = 13) was assessed with multiple electrode aggregometry (MEA), expressed as arbitrary units (U) derived from area-under-the-curve (AUC) in response to ADP, and inhibition of adenosine uptake by high-performance liquid chromatography (n = 7). Mean±SD AUC was 20.3 ± 8.2 U (2 h post-ticagrelor), 33.0 ± 18.3U (24 h), 56.6 ± 30.6U (48 h), 61.4 ± 20.2U (72 h), 82.8 ± 24.2U (96 h) and 96.0 ± 15.3U (120 h). There was a significant difference between 72 h and 120 h (p = .007), but not between 96 h and 120 h (p > .99). By 96 h, all patients had AUC >31U, an accepted cutoff below which surgical bleeding risk is increased. Adenosine uptake showed no significant differences between the timepoints. These data suggest it takes 4 days for platelet reactivity to recover sufficiently after cessation of ticagrelor to avoid the excess risk of CABG-related bleeding. Discontinuing ticagrelor had no measurable effect on cellular adenosine uptake.

A Systematic Review of 4D-Flow MRI Derived Mitral Regurgitation Quantification Methods.

Background: Four-dimensional flow cardiac magnetic resonance (4D flow CMR) is an emerging non-invasive imaging technology that can be used to quantify mitral regurgitation (MR) volume. Current methods of quantification have demonstrated limitations in accurate analysis, particularly in difficult cases such as complex congenital heart disease. 4D flow CMR methods aim to circumvent these limitations and allow accurate quantification of MR volume even in complex cases. This systematic review aims to summarize the available literature on 4D flow CMR MR quantification methods and examine their ability to accurately classify MR severity. Methods: Structured searches were carried out on Medline and EMBASE in December 2018 to identify suitable research outcome studies. The titles and abstracts were screened for relevance, with a third adjudicator utilized when study suitability was uncertain. Results: Seven studies met the eligibility criteria and were included in the systematic review. The most widely used 4D flow MRI method was retrospective valve tracking (RVT) which was examined in five papers. The key finding of these papers was that RVT is a reliable and accurate method of regurgitant volume quantification. Conclusions: MR quantification through 4D flow MRI is both feasible and accurate. The evidence gathered suggests that for MR assessment, 4D flow MRI is potentially as accurate and reliable to echocardiography and may be complementary to this technique. Further work on MR quantification 4D flow image analysis is needed to determine the most accurate analysis technique and to demonstrate 4D flow MRI as a predictor of clinical outcome. PROSPERO Registration Number: CRD42019122837, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019122837.

Sutureless aortic valve prostheses.

Conventional surgical aortic valve replacement (AVR) is the 'gold standard' for treatment of severe or symptomatic aortic valve stenosis. The increasing age of patients and increasing comorbidities has led to the development of procedures to minimise operative time and reduce risks of surgery. One method of reducing operative times is the use of sutureless aortic valves (SU-AVR). We examine the current literature surrounding the use of SU-AVR. Alternatives to AVR are SU-AVR, sometimes referred to as rapid deployment valves, or transcatheter aortic valve implantation (TAVI). TAVI has been demonstrated to be superior over medical therapy in patients deemed inoperable and non-inferior in high and intermediate-risk patients compared with surgical AVR. However, the lack of excision of the calcified aortic valve and annulus raises concerns regarding long-term durability and possibly thromboembolic complications. TAVI patients have increased rates of paravalvular leaks, major vascular complications and pacemaker implantation when compared with conventional AVR. SU-AVR minimises the need for suturing, leading to reduced operative times, while enabling complete removal of the calcified valve. The increase in use of SU-AVR has been mostly driven by minimally invasive surgery. Other indications include patients with a small and/or calcified aortic root, as well as patients requiring AVR and concomitant surgery. SU-AVR is associated with decreased operative times and possibly improved haemodynamics when compared with conventional AVR. However, this has to be weighed against the increased risk of paravalvular leak and pacemaker implantation when deciding which prosthesis to use for AVR.

Results of mechanical versus tissue AVR: caution in young patients with tissue AVR.

The first aortic valve prosthesis, implanted more than 50 years ago, was a mechanical prosthesis (ball-and-cage design). Over the ensuing decades, tissue prostheses and new mechanical designs were introduced to mitigate the need for anticoagulation with its associated side effects. Tissue and mechanical heart valve prostheses were compared in two head-to-head randomised control trials. Both of these confirmed that mechanical prostheses were durable but patients suffered anticoagulant-related bleeds. Patients who received a tissue prosthesis were more likely to suffer prosthetic dysfunction and require reoperation. This trend was stronger in younger patients. Since the publication of those two trials, several large retrospective studies using data from meta-analyses of published papers or registries have failed to show a survival advantage of either prostheses when implanted in the aortic position in younger patients. This equipoise has been reflected in the heart valve disease guidelines published by European and US societies. In recent years, the primacy of patient choice, the rapid increase in life expectancy of populations, the increased incidence of atrial fibrillation with requirement for anticoagulation, the advent of transcatheter techniques to treat degenerating tissue valves as well as advances in anticoagulant therapy and in new tissue and to a lesser extent mechanical prosthetic design continue to influence choice of aortic valve prosthesis in younger patients undergoing aortic valve replacement.