Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a very common long-term condition and powerful risk factor for cardiovascular disease (CVD). Low-dose aspirin is of proven benefit in the secondary prevention of myocardial infarction (MI) and stroke in people with pre-existing CVD. However, in people without CVD, the rates of MI and stroke are much lower, and the benefits of aspirin in the primary prevention of CVD are largely balanced by an increased risk of bleeding. People with CKD are at greatly increased risk of CVD and so the absolute benefits of aspirin are likely to be greater than in lower-risk groups, even if the relative benefits are the same. Post hoc evidence suggests the relative benefits may be greater in the CKD population but the risk of bleeding may also be higher. A definitive study of aspirin for primary prevention in this high-risk group, recommended by the National Institute for Health and Care Excellence (NICE) in 2014, has never been conducted. The question has global significance given the rising burden of CKD worldwide and the low cost of aspirin. METHODS: ATTACK is a pragmatic multicentre, prospective, randomised, open-label, blinded endpoint adjudication superiority trial of aspirin 75 mg daily vs. standard care for the primary prevention of CVD in 25,210 people aged 18 years and over with CKD recruited from UK Primary Care. Participants aged 18 years and over with CKD (GFR category G1-G4) will be identified in Primary Care and followed up using routinely collected data and annual questionnaires for an average of 5 years. The primary outcome is the time to first major vascular event (composite of non-fatal MI, non-fatal stroke and cardiovascular death [excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage]). Deaths from other causes (including fatal bleeding) will be treated as competing events. The study will continue until 1827 major vascular events have occurred. The principal safety outcome is major intracranial and extracranial bleeding; this is hypothesised to be increased in those randomised to take aspirin. The key consideration is then whether and to what extent the benefits of aspirin from the expected reduction in CVD events exceed the risks of major bleeding. DISCUSSION: This will be the first definitive trial of aspirin for primary CVD prevention in CKD patients. The research will be of great interest to clinicians, guideline groups and policy-makers, in the UK and globally, particularly given the high and rising prevalence of CKD that is driven by population ageing and epidemics of obesity and diabetes. The low cost of aspirin means that a positive result would be of relevance to low- and middle-income countries and the impact in the developed world less diluted by any inequalities in health care access. TRIAL REGISTRATION: ISRCTN: ISRCTN40920200 . EudraCT: 2018-000644-26 . CLINICALTRIALS: gov: NCT03796156.

Pulsatile sterile abscess in the left breast following transapical transcatheter aortic valve implantation: a case report.

BACKGROUND: Over the last decade, transcatheter treatment of degenerative aortic valve stenosis has been established as an alternative to surgical aortic valve replacement. Late complications of transcatheter treatment of aortic stenosis (AS) are infrequent. CASE SUMMARY: We report an 87-year-old woman treated successfully with 23 mm Sapien 3 transapical transcatheter aortic valve implantation for severe AS. She presented 4 months later with a pulsatile mass in the left breast. After exclusion of other diagnoses, the mass was attributed to a sterile abscess communicating with the pericardial cavity due to post-operative chest infection and pleural effusion. Multimodality imaging helped to define the anatomy of the abscess and the mechanism of the pulsation. DISCUSSION: This is the first report of a pulsatile sterile abscess occurring as a complication of transapical aortic valve implantation. Multimodality imaging confirmed that the pulsation was due to extension of the abscess into the pericardial cavity, excluded direct communication with the left ventricle, and facilitated successful non-surgical management.

Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary.

Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.

Management of Periprosthetic Joint Infection: The More We Learn, the Less We Know.

BACKGROUND: Despite the tremendous and long-standing success of total hip arthroplasty and total knee arthroplasty as treatments for end-stage arthritis, periprosthetic joint infection (PJI) remains a rare but feared complication of these procedures. METHODS: This review highlights some of the difficulties inherent to studying PJI. These include the difficulty in powering studies to capture this relatively uncommon complication, as well as the heterogeneity in clinical presentation and manifestations associated with the diagnosis and treatment of PJI. CONCLUSION: We suggest an algorithm for moving forward with new research in an attempt to answer the challenging questions facing the arthroplasty community regarding PJI.

Impact of call-to-balloon time on 30-day mortality in contemporary practice.

OBJECTIVE: Studies reporting an association between treatment delay and outcome for patients with ST segment elevation myocardial infarction (STEMI) have generally not included patients treated by a primary percutaneous coronary intervention (PPCI) service that systematically delivers reperfusion therapy to all eligible patients. We set out to determine the association of call-to-balloon (CTB) time with 30-day mortality after PPCI in a contemporary series of patients treated within a national reperfusion service. METHODS: We analysed data on 16 907 consecutive patients with STEMI treated by PPCI in England and Wales in 2011 with CTB time of ≤6 hours. RESULTS: The median CTB and door-to-balloon times were 111 and 41 min, respectively, with 80.9% of patients treated within 150 min of the call for help. An out-of-hours call time (58.2% of patients) was associated with a 10 min increase in CTB time, whereas inter-hospital transfer for PPCI (18.5% of patients) was associated with a 49 min increase in CTB time. CTB time was independently associated with 30-day mortality (p<0.0001) with a HR of 1.95 (95% CI 1.54 to 2.47) for a CTB time of >180-240 min compared with ≤90 min. The relationship between CTB time and 30-day mortality was influenced by patient risk profile with a greater absolute impact of increasing CTB time on mortality in high-risk patients. CONCLUSION: CTB time is a useful metric to assess the overall performance of a PPCI service. Delays to reperfusion remain important even in the era of organised national PPCI services with rapid treatment times and efforts should continue to minimise treatment delays.

Transcatheter Closure of Iatrogenic VSDs after Aortic Valve Replacement Surgery: 2 Case Reports and a Literature Review.

We report 2 new cases of transcatheter closure of iatrogenic ventricular septal defects after aortic valve replacement surgery, together with our finding, in a literature review, of 9 additional patients who had undergone this procedure from 2004 through 2013. In all 11 cases, transcatheter device closure was indicated for a substantial intracardiac shunt with symptomatic heart failure, and such a device was successfully deployed across the iatrogenic ventricular septal defect, with clinical improvement. Our review suggests that transcatheter closure of iatrogenic ventricular septal defects in patients with previous aortic valve replacement surgery is a safe and effective treatment option, providing anatomic defect closure and relief of symptoms in the short-to-medium term.

Fracture of an uncemented tantalum patellar component.

A 62-year-old man presented with the acute, atraumatic onset of pain 3 years after uncemented right total knee arthroplasty. He complained of new mechanical locking with the knee held in extension on examination and unable to flex the knee. On the plain radiographs, the patellar component peg was fractured and the plate was dislocated. The knee was immobilized, and revision to a cemented 3-peg component was performed. Fracture of a single-peg, tantalum-backed uncemented patellar component has not been described. Clinical suspicion for this should be given in the setting of acute locking. We recommend revision with a cemented polyethylene component.

10-Year Mortality Outcome of a Routine Invasive Strategy Versus a Selective Invasive Strategy in Non-ST-Segment Elevation Acute Coronary Syndrome: The British Heart Foundation RITA-3 Randomized Trial.

BACKGROUND: The RITA-3 (Third Randomised Intervention Treatment of Angina) trial compared outcomes of a routine early invasive strategy (coronary arteriography and myocardial revascularization, as clinically indicated) to those of a selective invasive strategy (coronary arteriography for recurrent ischemia only) in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). At a median of 5 years' follow-up, the routine invasive strategy was associated with a 24% reduction in the odds of all-cause mortality. OBJECTIVES: This study reports 10-year follow-up outcomes of the randomized cohort to determine the impact of a routine invasive strategy on longer-term mortality. METHODS: We randomized 1,810 patients with NSTEACS to receive routine invasive or selective invasive strategies. All randomized patients had annual follow-up visits up to 5 years, and mortality was documented thereafter using data from the Office of National Statistics. RESULTS: Over 10 years, there were no differences in mortality between the 2 groups (all-cause deaths in 225 [25.1%] vs. 232 patients [25.4%]: p = 0.94; and cardiovascular deaths in 135 [15.1%] vs. 147 patients [16.1%]: p = 0.65 in the routine invasive and selective invasive groups, respectively). Multivariate analysis identified several independent predictors of 10-year mortality: age, previous myocardial infarction, heart failure, smoking status, diabetes, heart rate, and ST-segment depression. A modified post-discharge Global Registry of Acute Coronary Events (GRACE) score was used to calculate an individual risk score for each patient and to form low-risk, medium-risk, and high-risk groups. Risk of death within 10 years varied markedly from 14.4 % in the low-risk group to 56.2% in the high-risk group. This mortality trend did not depend on the assigned treatment strategy. CONCLUSIONS: The advantage of reduced mortality of routine early invasive strategy seen at 5 years was attenuated during later follow-up, with no evidence of a difference in outcome at 10 years. Further trials of contemporary intervention strategies in patients with NSTEACS are warranted. (Third Randomised Intervention Treatment of Angina trial [RITA-3]; ISRCTN07752711).

Fractional flow reserve versus angiography in guiding management to optimize outcomes in non-ST-elevation myocardial infarction (FAMOUS-NSTEMI): rationale and design of a randomized controlled clinical trial.

BACKGROUND: In patients with acute non-ST-elevation myocardial infarction (NSTEMI), coronary arteriography is usually recommended; but visual interpretation of the angiogram is subjective. We hypothesized that functional assessment of coronary stenosis severity with a pressure-sensitive guide wire (fractional flow reserve [FFR]) would have additive diagnostic, clinical, and health economic utility as compared with angiography-guided standard care. METHODS AND DESIGN: A prospective multicenter parallel-group 1:1 randomized controlled superiority trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement) will be conducted. Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group. All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity including culprit and nonculprit lesions. Fractional flow reserve will be disclosed to guide treatment in the FFR-guided group but not disclosed in the "angiography-guided" group. In the FFR-guided group, an FFR ≤0.80 will be an indication for revascularization by percutaneous coronary intervention or coronary artery bypass surgery, as appropriate. The primary outcome is the between-group difference in the proportion of patients allocated to medical management only compared with revascularization. Secondary outcomes include the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure, quality of life, and health care costs. The minimum and average follow-up periods for the primary analysis are 6 and 18 months, respectively. CONCLUSIONS: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes.

Patient-specific instruments for total knee arthroplasty.

The use of patient-specific instruments for total knee arthroplasty shifts computer navigation for bone landmark registration and implant positioning from the intraoperative to the preoperative setting. Each system requires preoperative MRI or CT, with specifications determined by the instrument manufacturer. The marketed advantages of patient-specific instruments include greater accuracy in coronal alignment with fewer outliers, no need for instrumentation of the intramedullary canal, reduced surgical time, lower hospital costs, and improved clinical outcomes. The few published results of these instruments suggest minimal gains obtained in hospital logistics variables and minimal evidence of improvement in either alignment or patient outcomes. Disadvantages of patient-specific instruments include increased costs for imaging and instrument fabrication as well as increased preoperative time required for surgical planning and reviewing the instrument plans, and the learning curve for the surgeon to work with the engineers and use these instruments intraoperatively. It is also necessary to have a set of standard instruments available in case the patient-specific instruments do not work properly. Additional data are required before deciding whether these instruments should be recommended.

Can tantalum cones provide fixation in complex revision knee arthroplasty?

BACKGROUND: The best method for managing large bone defects during revision knee arthroplasty is unknown. Metaphyseal fixation using porous tantalum cones has been proposed for severe bone loss. Whether this approach achieves osseointegration with low complication rates is unclear. QUESTIONS/PURPOSES: We therefore asked: (1) What is the risk of infection in revision knee arthroplasty with large bone defects reconstructed with porous tantalum cones? (2) What is the rate of osseointegration with these cones? (3) What is the rate of loosening and reoperation? (4) Is knee function restored? METHODS: We retrospectively reviewed 27 patients who had 33 tantalum cones (nine femoral, 24 tibial) implanted during 27 revision knee arthroplasties. There were 14 women and 13 men with a mean age of 64.6 years. Preoperative diagnosis was reimplantation for infection in 13 knees, aseptic loosening in 10, and wear-osteolysis in four. Patients were evaluated clinically and radiographically using the score systems of the Knee Society and followed for a minimum of 2 years (mean, 3.3 years; range, 2-5.7 years). RESULTS: One knee with two cones was removed for infection. All but one cone showed osseointegration. One knee was revised for femoral cone and component loosening. There was one reoperation for femoral shaft fracture and one for superficial dehiscence. The mean Knee Society pain score improved from 40 points preoperatively to 79 points postoperatively. The mean function score improved from 19 points to 47 points. CONCLUSIONS: Our observations suggest metaphyseal fixation with tantalum cones can be achieved. Longer-term followup is required to determine whether the fixation is durable.

Pseudoaneurysm of the left ventricle following apical approach TAVI.

Symptomatic severe aortic stenosis carries a two year survival of only 50%. However many patients are unsuitable for conventional aortic valve replacement as they are considered too high risk due to significant co-morbidities. Transcatheter Aortic Valve Implantation (TAVI) offers a viable alternative for this high risk patient group, either by the femoral or apical route. This article reports a case of a pseudoaneurysm of the left ventricle following an apical approach TAVI in an elderly lady with severe aortic stenosis. To our knowledge pseduoaneuryms of the left ventricle have been reported infrequently in the literature and has yet to be established as a recognised complication of TAVI.