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.

Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK).

BACKGROUND: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. METHODS: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. RESULTS: Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with  lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. CONCLUSIONS: Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

Inflammation in aortic surgery: postoperative evolution of biomarkers according pathologies and segments of the aorta.

OBJECTIVES: Aortic pathologies often present with elevated inflammatory biomarkers due to the nature of the disease. Open aortic surgery causes significant trauma to the body due to often mandatory ischemic periods, long cardiopulmonary bypass times and polytransfusion. We aim to determine postoperative trends on inflammation biomarkers for different aortic pathologies and type of surgery in different segments of the aorta. METHODS: Retrospective review of prospectively collected data of 193 consecutive patients who underwent aortic surgery in our centre between 2017 and 2021, grouped according to the type of aortic intervention: (1) Type A aortic dissection (AD) repair with ascending aorta/hemiarch replacement, (2) Aortic root replacement (ARR), (3) Aortic arch + Frozen elephant trunk (FET), (4) Descending thoracic aorta (DTA)/Thoraco-Abdominal aortic repair (TAA). Primary outcomes were daily values of white blood cells (WBC) and C-Reactive Protein (CRP) during the first 15 postoperative days. RESULTS: All groups had a similar inflammatory peak in the first 2-4 days (WBC 12-15 × 109 c/L). AD and FET groups show similar trends with WBC and CRP peaks on days 2 and 10. The ARR group didn't experience the 2nd peak as most patients were already discharged. DTA/TAA patients experienced a more prolonged inflammatory response, reaching a plateau by day 5-10. AD group shows the highest WBC levels and the DTA/TAAA group the highest CRP levels. CRP levels remain elevated (100-200 mg/L) in all groups after 15 postoperative days. CONCLUSIONS: Inflammatory biomarkers show different postoperative trends depending on the clinical presentation and complexity of the aortic procedure performed. Further understanding of the inflammatory response to different aortic pathologies and surgical procedures will permit reduction on the liberal use of antibiotics that this cohort of patients are usually exposed to. An earlier version of the data included in this manuscript was presented as Oral Abstract in the UK Society of Cardiothoracic Surgery Annual meeting in 2021.