Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery. Aguiar CM, Gawdat K, Legere S, Marshall J, Hassan A, Kienesberger PC, Pulinilkunnil T, Castonguay M, Brunt KR, Legare JF. J Transl Med. 2019 Dec 10;17(1):413. doi: 10.1186/s12967-019-02162-5.


The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome.


Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry.


A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16-). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio).


Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

Role of branched-chain amino acid-catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis. Biswas D, Duffley L, Pulinilkunnil T. FASEB. 2019 May 14:fj201802842RR. doi: 10.1096/fj.201802842RR.

Beyond their contribution as fundamental building blocks of life, branched-chain amino acids (BCAAs) play a critical role in physiologic and pathologic processes. Importantly, BCAAs are associated with insulin resistance, obesity, cardiovascular disease, and genetic disorders. However, several metabolome-wide studies in recent years could not attribute alterations in systemic BCAAs as the sole driver of endocrine perturbations, suggesting that a snapshot of global BCAA changes does not always reveal the underlying modifications. Because enzymes catabolizing BCAAs have a unique distribution, it is plausible that the tissue-specific roles of BCAA-catabolic enzymes could precipitate changes in systemic BCAA levels, flux, and action. We review the genetic and pharmacological approaches dissecting the role of BCAA-catabolic enzyme dysfunctions. We summarized emerging evidence on BCAA metabolic intermediates, tissue specificity of BCAA-catabolizing enzymes, and crosstalk between different metabolites in driving metabolic maladaptation in health and pathology. This review substantiates the understanding that tissue-specific dysfunction of the BCAA-catabolic enzymes and accumulating intermediary metabolites could act as better surrogates of metabolic imbalances, highlighting the biochemical communication among the nutrient triad of BCAAs, glucose, and fatty acid. Read here

Impact of Obesity on Postoperative Outcomes following cardiac Surgery (The OPOS study): rationale and design of an investigator-initiated prospective study. Aguiar C, MacLeod J, Yip A, Melville S, Légaré JF, Pulinilkunnil T, Kienesberger P, Brunt K, Hassan A. BMJ Open. 2019 Mar 3;9(3):e023418. doi: 10.1136/bmjopen-2018-023418.


Increasing levels of obesity worldwide have led to a rise in the prevalence of obesity-related complications including cardiovascular risk factors such as diabetes, hypertension and dyslipidaemia. Healthcare providers believe that overweight and obese cardiac surgery patients are more likely to experience adverse postoperative outcomes. The body mass index (BMI) is the primary measure of obesity in clinical practice, without accounting for a patient’s level of cardiopulmonary fitness or muscle mass. The objective of this study is to determine whether fitness capacity of obese cardiac surgical patients and biomarkers, alone or in combination, will help identify patients at risk for adverse outcomes when undergoing cardiac surgery.


Patients between the ages of 18 and 75 years undergoing elective cardiac surgery are consented to participate in this prospective observational study. Patients will be invited to participate in measures of obesity, functional capacity and exercise capacity assessments, quality of life questionnaires, and blood and tissue sampling for biomarker analysis. The endpoints evaluated are measures other than BMI that could be predictive of short-term and long-term postoperative outcomes. Clinical outcomes of interest are prolonged ventilation, hospital length of stay, renal failure and all-cause mortality. Biomarkers of interest will largely focus on metabolism (lipids, amino acids) and inflammation (adipokines, cytokines and chemokines).


This study has been approved by the institutional review board at the Horizon Health Network. On completion of the study, the results shall be disseminated through conference presentations and publications in peer-reviewed journals. Additionally, the report shall also be diffused more broadly to the general public and the cardiovascular community.