Monocyte subsets in atrial fibrillation with preserved left ventricular function

Shahid, Farhan (2021). Monocyte subsets in atrial fibrillation with preserved left ventricular function. University of Birmingham. Ph.D.

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Abstract

Introduction: Atrial fibrillation is the commonest arrhythmia in the cardiovascular system. It can have debilitating effects, including life changing thromboembolic stroke. Monocytes and their subsets have proven to be both beneficial and detrimental in heart failure and coronary artery disease. Less is known regarding their role in atrial fibrillation. The aims of this thesis were to study the following parameters in patients with atrial fibrillation and preserved left ventricular function: 1) monocyte subset numbers, 2) monocyte subset expression of surface receptors for inflammation, 3) crosstalk between monocytes and platelets in the formation of monocyte-platelet aggregates (MPAs), 4) markers of cardiac fibrosis, 5) utility of Spironolactone to aid in improved exercise capacity in this cohort of patients.

Methods: Monocyte subsets were analysed by flow cytometry on venous blood samples in 250 patients with permanent atrial fibrillation and preserved left ventricular function who were double blindly allocated to spironolactone or placebo and followed up in clinic at specified time intervals. The subsets were analysed at 12 and 24 months from the treatment allocation. Plasma levels of cardiac markers of fibrosis were analysed by ELISA at baseline, 12 months and 24 months. The patients underwent cardiopulmonary exercise testing, 6-minute walk test and quality of life assessment at set time intervals during the 2-year study period to assess their relationship to monocyte subsets.

Results: CD16 expression on Mon3 subset was associated with a higher Peak VO2 and CD42 expression on MPA associated with Mon3 with a reduced exercise capacity (p value of 0.001 and 0.026 respectively). Quality of life and hospitalisations were unaffected by monocyte subsets. Spironolactone did not impact on primary and secondary outcomes of the study and monocyte characteristics. The markers of cardiac fibrosis did not explain the mechanistic role by which Mon3 influences exercise capacity in this patient population.

Conclusion: Differences in monocyte cell surface marker expression influence exercise capacity and functional status in patients with atrial fibrillation and preserved left ventricular function. Spironolactone, however, does not affect such study parameters when compared to placebo. Further studies are required to decipher the mechanisms by which monocyte cell surface markers influence exercise capacity.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):