Mechanisms of Cardiovascular Disease

High risk coronary plaque
A multimodality approach combining CT, OCT, IVUS, PET and histology with information on inflammation and shear stress has identified “high risk” coronary plaques that are at risk for rupture. Current efforts focus on whether this high risk CT phenotype can identify the patients at greatest risk for cardiovascular events.

Napkin Ring Sign (NRS) on coronary CT (left panels) with histologic correlation (right panel). NRS is a high risk plaque
feature associated with cardiovascular events.

Maurovich-Horvat P et al. Comprehensive plaque assessment by coronary CT angiography. Nat Rev Cardiol 2014;11(7):390-402.

Puchner SB et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol 2014;64(7):684-92.

Amygdalar, arterial, and bone-marrow uptake of F-FDG in individuals with and without subsequent cardiovascular disease events.


Axial views of amygdala (upper left and right), coronal views of aorta (middle left and right), and coronal views of bone marrow (lower left and right) are shown. .⁸F-FDG uptake was increased in the amygdala, bone marrow, and arterial wall (aorta), in a patient who experienced an ischemic stroke during the follow-up period (right) compared with a patient who did not (left). .⁸F-FDG=.⁸F fluorodeoxyglucose. SUV=standardised uptake value. TBR=target-to-background ratio. Tawakol et al Lancet 2017.

In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings.

Tawakol A et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet 2017.

Coronary plaque and arterial inflammation in HIV
Multi-modal, multi-tissue imaging provides a unique opportunity to evaluate pathological disorders that involve multiple tissues and organs. One recent example of such imaging is in the evaluation of mechanisms linking HIV infection to atherosclerosis. Studies from our group demonstrated that the increased risk of cardiovascular events in HIV may be due to increased arterial inflammation on PET and coronary plaque on CT. Several on-going RCTs are assessing the impact of complementary therapies on arterial inflammation on PET and atherosclerotic plaque structure on CT in HIV.

Subramanian S et al. Arterial inflammation in patients with HIV. JAMA 2012;308(4):379-86.

Zanni MV et al. Effects of antiretroviral therapy on immune function and arterial inflammation in treatment-naive patients with human immunodeficiency virus infection. JAMA Cardiol 2016;1(4):474-80.

The figure shows positron emission tomography,
computed tomography images of the carotid arteries
following left carotid field radiotherapy. The patient had
a TIA from a critical left common carotid stenosis and
angiographic pre- and post-intervention are also shown.

Carotid plaque and the risk of stroke after radiation therapy
There is an increased risk of stroke after radiation therapy for head and neck cancer. The mechanisms for the increased risk of stroke are unclear but data suggest a pathway from an increase in inflammation leading to accelerated atherosclerosis (Image). Multi-modal, multi-tissue imaging provides a unique opportunity to characterize this pathway from inflammation to atherosclerosis, to identify the risk factors that drive atherosclerosis and to consider interventions that may reduce the risk of stroke in this vulnerable population.

The risk of heart failure among persons living with HIV
There is an increased risk of heart failure among individuals living with HIV. The mechanisms for the increased risk are not completely clear but data suggest a pathway from increased intramyocardial fat and fibrosis leasing to stiffening of the myocardium and diastolic function. However, these mechanisms are poorly characterized. We are using a combination of tissue characterization techniques with MR to better characterize these pathological mechanisms among persons living with HIV.

Janjua et al, HIV Infection and Heart Failure Outcomes in Women. J Am Coll Cardiol. 2017 Jan 3;69(1):107-108.


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