Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Extracorporeal Life Support for Refractory Cardiac Arrest from Accidental Hypothermia: A 10-Year Experience in Edinburgh.

BACKGROUND: Cardiac arrest caused by accidental hypothermia is a rare phenomenon with a significant mortality rate if untreated. The consensus is that these patients should be rewarmed with extracorporeal life support (ECLS) with the potential for excellent survival and neurologic outcomes. However, given the lack of robust data and clinical trials, the optimal management of such patients remains elusive. OBJECTIVE: In this single-center study, we looked at the outcomes of all adult patients undergoing salvage ECLS for cardiac arrest caused by accidental hypothermia over a 10-year period from June 2006 to June 2016. METHODS: These data were obtained from the Royal Infirmary of Edinburgh cardiothoracic surgery database. The patients' hard copy case notes, TrakCare (InterSystems Corp, Cambridge, MA), picture archiving and communications system (PACS), and WardWatcher databases were used to cross-check the accuracy of the acquired data. RESULTS: Eleven patients met the inclusion criteria. The etiology of hypothermia was exposure to cold air (64%) and cold water immersion (36%). Two (18%) were treated with extracorporeal membrane oxygenation and the rest with cardiopulmonary bypass. The mean age was 51 years (range 32-73), and the mean core body temperature on admission was 20.6°C (range <18-24°C). The overall survival rate to hospital discharge was 72%, with 75% of survivors having no chronic neurologic impairment. CONCLUSION: Our case series shows the remarkable salvageability of patients suffering prolonged cardiac arrest caused by accidental hypothermia, particularly in the absence of asphyxia, trauma, or severe hyperkalemia. ECLS is a safe and effective rewarming treatment and should be used to aggressively manage this patient group.

Factor XI deficiency: incidental diagnosis post coronary artery bypass graft.

Severe Factor XI (FXI) deficiency is defined when the activated partial thromboplastin time is prolonged and its activation is <1-15 UdL(-1) in plasma. It is inherited as an autosomal recessive trait but can be acquired. In severe deficiency the bleeding diathesis is normally injury related. This particularly occurs during surgical procedures and trauma involving tissues rich in fibrinolytic activators. Cardiopulmonary bypass induces transient abnormalities in haemostasis which can cause a postoperative bleeding diathesis. Once treated, it does not appear to be a contraindication to cardiac procedures. Conversely, acquired deficiencies are more insidious being incidentally diagnosed during routine laboratory investigations and might be triggered by an inhibitory agent. We present a case of an uncomplicated 12-month delayed diagnosis of Factor XI deficiency following coronary artery bypass grafting and sternal rewiring. The potential risks if undiagnosed and the uncharacteristic clinical history of our case are discussed.

Pacemaker lead thrombosis - a rare cause of breathlessness.

As the number of pacemaker insertions increases to manage numerous cardiac arrhythmias, the number of complications is also increasing as a result. More common complications such as infection and lead displacement are routinely discussed with patients before they undergo the procedure. However rare complications such as superior vena cava syndrome are not discussed during the consenting period. But they do occur, as seen in this case of a 69-year-old male. This fit and active man had a right-sided dual-chamber pacemaker inserted due to sinus node disease and presented 5 years later with symptoms suggestive of superior vena cava obstruction (SVCO). Despite anticoagulation and before surgical intervention could be performed, the patient developed a right-sided chylothorax which was drained. An autologous pericardial patch repair of the SVC and a thrombectomy of SVC clots was subsequently performed. This was only partially successful and the SVCO recurred. A low fatty chain diet was initiated to manage the chylothorax, which remains stable. This rare complication has left the patient with a small pleural effusion and chronic pleural thickening. They can still exercise with mild breathlessness. The management of such a complication, which requires the input of many specialists, is challenging and often does not completely resolve all symptoms. For this reason, superior vena cava obstruction should be considered as a risk during the consenting procedure for a pacemaker insertion.

Sex-related Differences among Patients Undergoing Surgical Aortic Valve Replacement - A Propensity Score Matched Study.

OBJECTIVES: We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS: Data from two prospective registries, INDURE and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS: Females had a lower body mass index (BMI; median 27.1 vs 28.0 kg/m2; p = 0.008), fewer bicuspid valves (52% vs 59%; p = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; p < 0.001) and STS score (mean 1.6 vs 0.9%; p < 0.001), were more often in NYHA class III/IV (47% vs 30%; p < 0.001) and angina CCS III/IV (8.2% vs 4.4%; p < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; p = 0.028) compared to males. These differences vanished after PSM, except for EuroSCORE II and STS scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, p < 0.001). There were no differences in the length of hospital stay (median 8 days) or ICU stay (median 24 vs 25 hours) between both sexes. At two years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS: Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis.

BACKGROUND: The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. METHODS AND RESULTS: Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001). CONCLUSIONS: Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Post-traumatic Left Ventricular Apical Aneurysm With Endoluminal Thrombus.

Here, we report a case of a 54-year-old man who presented with complications of a left ventricle apical aneurysm, which was the result of a myocardial infarction (MI). Interestingly, he sustained the MI following a cardiac contusion whilst playing rugby 32 years ago. He had another MI 10 years later, despite the presence of normal coronary angiography following the initial event, and presented with two episodes of sustained ventricular tachycardia over six months. The patient proceeded to surgical resection of the aneurysm and went on to make a good recovery.

Comparison of outcomes of trans-subclavian versus trans-apical approaches in transcatheter aortic valve implantation.

BACKGROUND: Many patients are unsuitable for conventional femoral transcatheter aortic valve implantation (TAVI) but there is limited evidence as to which alternative approach has the best outcomes. We compared clinical outcomes in patients undergoing trans-subclavian (TS) or trans-apical (TA) TAVI. METHODS: This was a national retrospective observational study of patients undergoing surgical TAVI in Scotland between January 2013 and March 2020. The pre-operative patient characteristics, intraoperative details and post-operative outcomes were compared between TS and TA cohorts using data from the National Institute of Cardiovascular Outcomes Research (NICOR) registry. RESULTS: Among 1055 patients who underwent TAVI, TS or TA access was used in 50 (4.7%) and 90 (8.5%) patients respectively. Self-expanding Medtronic Evolut R valves were used in 84% of TS procedures, while balloon-expandable Edwards SAPIEN valves were used in all TA procedures. The TS group had a lower mean logistic EuroSCORE than the TA group (27.31 ± 19.44% vs 34.92 ± 19.61% p = 0.029). The TS approach was associated with a higher incidence of moderate postprocedural aortic regurgitation (12.5% vs 2.4%, p = 0.025). There was no significant difference in 30-day, 1-year or overall all-cause mortality. CONCLUSIONS: Both trans-subclavian and trans-apical access are viable approaches for patients requiring non-transfemoral TAVI. Differences in peri-procedural indices reflect the disparate patient populations and factors governing prosthesis choice, and short- and long-term mortality was similar.

Uncovering the treatable burden of severe aortic stenosis in the UK.

OBJECTIVE: To estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK. METHODS: We adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). RESULTS: With a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile; the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management. CONCLUSIONS: These data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus.

BACKGROUND: Bioprosthetic valve thrombosis may have implications for valve function and durability. OBJECTIVES: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves. METHODS: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT. RESULTS: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake. CONCLUSIONS: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875).

Minimally invasive versus conventional sternotomy for Mitral valve repair: protocol for a multicentre randomised controlled trial (UK Mini Mitral).

INTRODUCTION: Numbers of patients undergoing mitral valve repair (MVr) surgery for severe mitral regurgitation have grown and will continue to rise. MVr is routinely performed via median sternotomy; however, there is a move towards less invasive surgical approaches.There is debate within the clinical and National Health Service (NHS) commissioning community about widespread adoption of minimally invasive MVr surgery in the absence of robust research evidence; implementation requires investment in staff and infrastructure.The UK Mini Mitral trial will provide definitive evidence comparing patient, NHS and clinical outcomes in adult patients undergoing MVr surgery. It will establish the best surgical approach for MVr, setting a standard against which emerging percutaneous techniques can be measured. Findings will inform optimisation of cost-effective practice. METHODS AND ANALYSIS: UK Mini Mitral is a multicentre, expertise based randomised controlled trial of minimally invasive thoracoscopically guided right minithoracotomy versus conventional sternotomy for MVr. The trial is taking place in NHS cardiothoracic centres in the UK with established minimally invasive mitral valve surgery programmes. In each centre, consenting and eligible patients are randomised to receive surgery performed by consultant surgeons who meet protocol-defined surgical expertise criteria. Patients are followed for 1 year, and consent to longer term follow-up.Primary outcome is physical functioning 12 weeks following surgery, measured by change in Short Form Health Survey (SF-36v2) physical functioning scale. Early and 1 year echo data will be reported by a core laboratory. Estimates of key clinical and health economic outcomes will be reported up to 5 years.The primary economic outcome is cost effectiveness, measured as incremental cost per quality-adjusted life year gained over 52 weeks following index surgery. ETHICS AND DISSEMINATION: A favourable opinion was given by Wales REC 6 (16/WA/0156). Trial findings will be disseminated to patients, clinicians, commissioning groups and through peer reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN13930454.

Percutaneous Repair of Ventricular Ruptures.

Acquired ventricular wall ruptures can be life-threatening. Depending on the pathological features and anatomy, surgical repair can be technically challenging and may be associated with high morbidity and mortality. We present 3 successful percutaneous repairs of different ruptures that used a variety of techniques. (Level of Difficulty: Advanced.).

Benefits of rapid deployment aortic valve replacement with a mini upper sternotomy.

BACKGROUND: Surgical aortic valve replacement (AVR) is currently deemed the gold standard of care for patients with severe aortic stenosis. Currently, most AVRs are safely performed through a full median sternotomy approach. With an increasingly elderly and high-risk patient population, major advances in valve technology and surgical technique have been introduced to reduce perioperative risk and post-operative complications associated with the full sternotomy approach, in order to ensure surgical AVR remains the gold standard. For example, minimally invasive approaches (most commonly via mini sternotomy) have been developed to improve patient outcomes. The advent of rapid deployment valve technology has also been shown to improve morbidity and mortality by reducing cardiopulmonary bypass and aortic cross-clamp times, as well as facilitating the use of minimal access approaches. Rapid deployment valves were introduced into our department at the Royal Infirmary of Edinburgh in 2014. The aim of this study is to investigate if utilising the combination of rapid deployment valves and a mini sternotomy minimally invasive approach resulted in improved outcomes in various patient subgroups. METHODS: Over a 3-year period, we identified 714 patients who underwent isolated AVR in our centre. They were divided into two groups: 61 patients (8.5%) were identified who received rapid deployment AVR via J-shaped mini upper sternotomy (MIRDAVR group), whilst 653 patients (91.5%) were identified who received either a full sternotomy (using a conventional prosthesis or rapid deployment valve) or minimally invasive approach using a conventional valve (CONVAVR group). We retrospectively analysed data from our cardiac surgery database, including pre-operative demographics, intraoperative times and postoperative outcomes. Outcomes were also compared in two different subgroups: octogenarians and high-risk patients. RESULTS: Pre-operative demographics showed that there were significantly more female and elderly patients in the MIRDAVR group. The MIRDAVR group had significantly reduced cardiopulmonary bypass (63.7 min vs. 104 min, p = 0.0001) and aortic cross-clamp times (47.3 min vs. 80.1 min, p = 0.0001) compared to the CONVAVR group. These results were particularly significant in the octogenarian population, who also had a reduced length of ICU stay (30.9 h vs. 65.6 h, p = 0.049). In high-risk patients (i.e. logistic EuroSCORE I > 10%), minimally invasive-rapid deployment aortic valve replacement is still beneficial and is also characterized by significantly shorter cardiopulmonary bypass time (69.1 min vs. 96.1 min, p = 0.03). However, post-operative correlations, such as length of ICU stay, become no more significant, likely due to serious co-morbidities in this patient group. CONCLUSION: We have demonstrated that minimally invasive rapid deployment aortic valve replacement is associated with significantly reduced cardiopulmonary bypass and aortic cross-clamp times. This correlation is much stronger in the octogenarian population, who were also found to have significantly reduced length of ICU stay. Our study raises the suggestion that this approach should be utilised more frequently in clinical practice, particularly in octogenarian patients.

Durability of bioprosthetic aortic valves in patients under the age of 60 years - rationale and design of the international INDURE registry.

BACKGROUND: There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. METHODS: The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20-22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life. DISCUSSION: INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018).

Inter-valvular fibrosa pseudo-aneurysm as a late complication after aortic valve surgery.

We describe the incidental finding of an inter-valvular fibrosa pseudo-aneurysm in the absence of infective endocarditis 12 years after a re-do operation for aortic valve replacement in a patient whose initial pathology was bicuspid aortic valve stenosis.

Detection and Prediction of Bioprosthetic Aortic Valve Degeneration.

BACKGROUND: Bioprosthetic aortic valve degeneration is increasingly common, often unheralded, and can have catastrophic consequences. OBJECTIVES: The authors sought to assess whether 18F-fluoride positron emission tomography (PET)-computed tomography (CT) can detect bioprosthetic aortic valve degeneration and predict valve dysfunction. METHODS: Explanted degenerate bioprosthetic valves were examined ex vivo. Patients with bioprosthetic aortic valves were recruited into 2 cohorts with and without prosthetic valve dysfunction and underwent in vivo contrast-enhanced CT angiography, 18F-fluoride PET, and serial echocardiography during 2 years of follow-up. RESULTS: All ex vivo, degenerate bioprosthetic valves displayed 18F-fluoride PET uptake that colocalized with tissue degeneration on histology. In 71 patients without known bioprosthesis dysfunction, 14 had abnormal leaflet pathology on CT, and 24 demonstrated 18F-fluoride PET uptake (target-to-background ratio 1.55 [interquartile range (IQR): 1.44 to 1.88]). Patients with increased 18F-fluoride uptake exhibited more rapid deterioration in valve function compared with those without (annualized change in peak transvalvular velocity 0.30 [IQR: 0.13 to 0.61] vs. 0.01 [IQR: -0.05 to 0.16] ms-1/year; p < 0.001). Indeed 18F-fluoride uptake correlated with deterioration in all the conventional echocardiographic measures of valve function assessed (e.g., change in peak velocity, r = 0.72; p < 0.001). Each of the 10 patients who developed new overt bioprosthesis dysfunction during follow-up had evidence of 18F-fluoride uptake at baseline (target-to-background ratio 1.89 [IQR: 1.46 to 2.59]). On multivariable analysis, 18F-fluoride uptake was the only independent predictor of future bioprosthetic dysfunction. CONCLUSIONS: 18F-fluoride PET-CT identifies subclinical bioprosthetic valve degeneration, providing powerful prediction of subsequent valvular dysfunction and highlighting patients at risk of valve failure. This technique holds major promise in the diagnosis of valvular degeneration and the surveillance of patients with bioprosthetic valves. (18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome [18F-FAABULOUS]; NCT02304276).

A 59-year-old woman with visible precordial pulsations.

CLINICAL INTRODUCTION: A retired 59-year-old woman presented to the cardiology clinic concerned with cardiac pulsations that were visible on her chest wall. These were not associated with dyspnoea, syncope or chest discomfort.Of note, 8 years previously, she complained of recurrent nocturnal diaphoresis and 5 kg weight loss. Blood sampling at that time revealed a microcytic anaemia, reactive thrombocytosis and raised inflammatory markers (erythrocyte sedimentation rate 99 mm/hour, C-reactive protein 161 mg/L). Following an episode of transient diplopia, ophthalmoscopy demonstrated a cotton wool spot in the left inferotemporal retinal arcade. She commenced a 2-year tapering course of 1 mg/kg prednisolone.On examination, she had a lean physique with a supine blood pressure of 162/60 mm Hg and palpable Corrigan's pulse. She had a prominent apical pulsation and a loud early diastolic murmur was present at the left sternal edge radiating to the apex. Echocardiography showed severe central aortic regurgitation and a dilated aortic root (see online supplementary figure 1). Cardiac CT was performed to clarify the diagnosis (figure 1).DC1SP110.1136/heartjnl-2017-312193.supp1Supplementary file 1 heartjnl;104/3/273/F1F1F1Figure 1Contrast-enhanced CT of the thorax at index presentation (A) and 6 months (B). Prospective ECG-gated cardiac CT angiogram (75% R-R interval) performed at 8 years from index presentation (C) with a stretched multiplanar reconstruction of the aortic annulus, aortic root and thoracic aorta (D). QUESTION: Which of the following diagnoses best explains this presentation?Ankylosing spondylitisTakayasu arteritisSalmonellosisIgG4-related aortitisGiant cell aortitis.

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

BACKGROUND: Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction. METHODS: We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and cardiac magnetic resonance imaging (CMR) using both late gadolinium enhancement (LGE) and ultrasmall superparamagnetic particles of iron oxide (USPIO). RESULTS: Systemic humoral inflammatory biomarkers (myeloperoxidase, interleukin-6, interleukin-8 and c-reactive protein) increased in the post-operative period with C-reactive protein concentrations plateauing by 48 h (median area under the curve (AUC) 7530 [interquartile range (IQR) 6088 to 9027] mg/L/48 h). USPIO-defined cellular myocardial inflammation ranged from normal to those associated with type 1 myocardial infarction (median 80.2 [IQR 67.4 to 104.8] /s). Plasma hs-cTnI concentrations rose by ≥50-fold from baseline and exceeded 10-fold the upper limit of normal in all patients. Two distinct patterns of peak cTnI release were observed at 6 and 24 h. After CABG surgery, new LGE was seen in 20% (n = 18) of patients although clinical peri-operative type 5 myocardial infarction was diagnosed in only 9% (n = 8). LGE was associated with the delayed 24-h peak in hs-cTnI and its magnitude correlated with AUC plasma hs-cTnI concentrations (r = 0.33, p < 0.01) but not systemic inflammation, myocardial inflammation or bypass time. CONCLUSION: Patients undergoing CABG surgery invariably have plasma hs-cTnI concentrations >10-fold the 99th centile upper limit of normal that is not attributable to inflammatory or ischemic injury alone. Peri-operative type 5 myocardial infarction is often unrecognised and is associated with a delayed 24-h peak in plasma hs-cTnI concentrations.

Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction.

OBJECTIVES: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI. METHODS: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues. RESULTS: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01). CONCLUSION: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions. TRIAL REGISTRATION NUMBER: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2).