Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy.

Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiology-specific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immune-mediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy.

Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers.

Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), ß2-microglobulin (ß2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), ß2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and ß2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this 'HAM-like' profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.

Infective endocarditis complicating transcatheter aortic valve implantation.

Infective endocarditis complicating transcatheter aortic valve implantation (TAVI-IE) is a relatively rare condition with an incidence of 0.2%-3.1% at 1 year post implant. It is frequently caused by Enterococci, Staphylococcus aureus and coagulase negative staphylococci While the incidence currently appears to be falling, the absolute number of cases is likely to rise substantially as TAVI expands into low risk populations following the publication of the PARTNER 3 and Evolut Low Risk trials. Important risk factors for the development of TAVI-IE include a younger age at implant and significant residual aortic regurgitation. The echocardiographic diagnosis of TAVI-IE can be challenging, and the role of supplementary imaging techniques including multislice computed tomography (MSCT) and positron emission tomography (18FDG PET) is still emerging. Treatment largely parallels that of conventional prosthetic valve endocarditis (PVE), with prolonged intravenous antibiotic therapy and consideration of surgical intervention forming the cornerstones of management. The precise role and timing of cardiac surgery in TAVI-IE is yet to be defined, with a lack of clear evidence to help identify which patients should be offered surgical intervention. Minimising unnecessary healthcare interventions (both during and after TAVI) and utilising appropriate antibiotic prophylaxis may have a role in preventing TAVI-IE, but robust evidence for specific preventative strategies is lacking. Further research is required to better select patients for advanced hybrid imaging, to guide surgical management and to inform prevention in this challenging patient cohort.

A Randomised Controlled Trial Comparing Three Different Radiofrequency Technologies: Short-Term Results of the 3-RF Trial.

OBJECTIVE: To date there has been no comparison of outcomes of endovenous radiofrequency (RF) devices. The 3-RF trial is the first randomised controlled trial of three commercially available RF ablation technologies. METHODS: Patients were recruited [182/302 patients with great saphenous vein (GSV) incompetence] into a prospective double blind randomised trial of Venefit, radiofrequency induced thermal therapy (RFITT), and endovenous radiofrequency (EVRF). The primary outcome measure was GSV closure (total/partial/failed) at six months. Secondary outcome measures included ablation times, complications, pain scores, analgesia requirements, and quality of life (QoL) scores to 12 months. RESULTS: Patients treated [180: Venefit (57), RFITT (64), EVRF (59)] were matched for age, sex, and vein characteristics. At six months, complete GSV closure was significantly better after Venefit and RFITT treatment (100% and 98%, respectively) compared with EVRF treatment (79%, p < .001). Mean treatment time was significantly faster for RFITT than for Venefit and EVRF (p < .0001). Euroqol 5D (EQ5D) visual analogue score (VAS) did not differ between groups at any time point. The only difference between groups in EQ5D domain scores was for the pain/discomfort domain at two weeks when significantly fewer EVRF patients reported no problems compared with Venefit and RFITT. This difference had disappeared at six and 12 months. The Aberdeen Varicose Vein Questionnaire (AVVQ) improved for all groups at six and 12 months compared with pre-treatment levels; however, there was no significant difference between groups. CONCLUSION: Compared with Venefit and RFITT, EVRF was associated with significant failure of truncal ablation at six months; however, clinical outcomes did not differ significantly at 12 months. clinicaltrials.gov identifier: NCT02441881, NHS Health Research Authority (Hampstead Research Ethics Committee) number: 14/LO/1232.

Advanced imaging improves the diagnosis of infective endocarditis.

Infective endocarditis is a heterogeneous condition whose incidence is rising. Despite advances in surgery and diagnostic methods, one-year mortality has not changed and it remains at 30%. Patients with prosthetic valve and intra-cardiac device-related endocarditis are being seen more frequently and this condition is difficult to diagnose with conventional microbiological and imaging techniques. The modified Duke criteria lack sensitivity in this group and should be supplemented with newer imaging techniques, including 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and single-photon emission computed tomography (SPECT). In this article, we discuss these techniques and their role in the diagnosis of infective endocarditis.

Poor adherence of randomised trials in surgery to CONSORT guidelines for non-pharmacological treatments (NPT): a cross-sectional study.

OBJECTIVE: To systematically assess adherence of randomised trials in surgery to Consolidated Standards of Reporting Trials (CONSORT) guidelines for non-pharmacological treatments (NPT). Surgical trials are considered more difficult to design and execute than pharmacological trials. Furthermore, the original CONSORT statement does not address some aspects that are vital to the transparent reporting of surgical trials. The CONSORT-NPT extension was designed to address these issues but adherence in medical and surgical journals has not been assessed. DESIGN: Cross-sectional study. SAMPLE: We identified eight general medical and eight surgical journals, indexed in PubMed and published in 2011, with the highest impact factors in their respective categories. MAIN OUTCOMES: Adherence to CONSORT statement and CONSORT-NPT extension items. RESULTS: We identified 54 surgical trials (22 published in medical journals and 32 in surgical journals). There were eight items for which there was less than 30% overall compliance (seven were specific to the CONSORT-NPT extension). These seven items are related to: a full description of the care providers, centres and blinding status in the abstract (n=7/54, 13%), eligibility criteria for centres performing the interventions (n=13/54, 24%), how adherence of care providers with the protocol was assessed or enhanced (n=7/54, 13%), how clustering by care providers or centres was addressed as it relates to sample size (n=3/54, 6%), how care providers were allocated to each group (n=9/54, 17%), how clustering by care providers or centres was addressed as it relates to statistical methods (n=2/54, 4%), a description of care providers (case volume, qualification, expertise, etc) and centres (volume) in each group (n=0/54, 0%). CONCLUSIONS: Adherence of surgical trials to CONSORT-NPT extension items is much poorer than to the standard CONSORT statement. Adherence also appears to be superior in general medical journals compared with surgical journals. Raising awareness and conducting qualitative research to identify areas for specific intervention will be important going forward.