Mimickers of chronic thromboembolic pulmonary hypertension on imaging tests: a review
Cardiac Aging Lab
Division of Kinesiology and Health
The Bruns lab is interested in the molecular mechanisms underlying heart disease and heart failure. Our research focuses on the impact of age on the failing heart, sex differences in heart failure development and treatment, exercise as medicine for heart failure, and the identification of new therapies for the treatment of cardiac disease.
dbruns1@uwyo.Edu Interested in being a student in the Cardiac Aging Lab? Please contact Dr.Bruns - we're always seeking motivated students! Collaborators Emily Schmitt, PhD. UW K&H. Circadian rhythm in the heartEvan Johnson, PhD. UW K&H Circadian rhythm and the aging kidneyKathleen Woulfe, PhD. UC-Denver Cardiology. Heart failure across the life courseCurrent Projects
The right heart: You're only as strong as your weakest link
The heart is a 4-chambered organ with two sides- the left heart which pumps to the periphery and the right heart which pumps through the lungs. Cardiac function is limited by the performance of its weakest ventricle, meaning that even in contexts of healthy left ventricular (LV) function, the heart can only perform as well as its weakest link. In the setting of many human diseases such as heart failure and pulmonary hypertension, this means that right ventricular (RV) function predicts survival. Our group is interested in understanding how the right heart fails and identifying therapeutic targets for the RV- a disease in which very few therapeutic options exist.
The aging right heart
Aging imparts known changes to the left heart- including hypertrophy, fibrosis, inflammation, and overall reduced cardiac function. How these changes impact the right heart remains unknown. Our group uses two models of right heart failure- high altitude induced pulmonary hypertension and a surgical model of disease (pulmonary artery banding; PAB)- to understand how the old heart remodels in a distinct manner from the young heart and how this may inform therapeutic approaches for older patients with heart failure. Specifically, we are currently testing an AMPK activator as novel therapy for the aging right heart.
Skeletal muscle dysfunction in heart failure
Heart failure is a systemic disease, with peripheral effects including skeletal muscle dysfunction. In human patients, muscle dysfunction manifests as exercise intolerance. We're interested in the molecular mechanisms underlying this skeletal muscle dysfunction, and the identification pf therapies to improve muscle function in young and old patients with heart failure.
Exercise as Medicine for Heart Failure
Regular endurance exercise is the best protection against development of cardiovascular disease. However, the precise molecular mechanisms for how exercise is so potently cardioprotective are not fully understood. Our group aims to understand how exercise improves cardiac function in the healthy, aging, and failing right hearts, as well as how commonly prescribed medications may interfere with exercise adaptations.
Heart Failure Across the Life-Course
Heart failure impacts patients of all ages- from pediatrics to geriatrics. The risk factors, disease development, and treatment outcomes differ by patient age and sex, suggesting that important differences exist that might impact therapeutic strategies. We aim to understand how age and sex impact disease development, and use these differences to develop personalized medicine for heart failure patients of all ages.
CTEPH Predictors Following Pulmonary Embolism
Risk for chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is associated with gender, delayed PE diagnosis, hypoxemia, heart load, D-dimer levels, and PE etiology. These findings were published in the Journal of the American Heart Association.
One of the most serious post-PE syndromes is CTEPH. A large variation in the rate of CTEPH has been reported and risk factors are not well understood.
The Contemporary Management and Outcomes in Patients With Venous Thromboembolism (COMMAND VTE) Registry-2 is a large cohort that recruited patients in Japan. In this study, patients (N=5197) with acute symptomatic venous thromboembolism between 2015 and 2020 at 31 sites were evaluated for CTEPH after acute PE (n=2787). The primary outcomes were the incidence of and risk factors for CTEPH.
Following a diagnosis of acute PE, the cumulative rates of CTEPH increased from 1.0% at 180 days to 1.7% at 1 year, 2.0% at 2 years, 2.3% at 3 years, and 2.4% at 4 and 5 years.
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Several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population for CTEPH after acute PE.
The patients with (n=48) and without (n=2739) CTEPH comprised 77.1% and 56.3% women (P =.004), their mean ages were 65.2±15.0 and 66.6±15.4 years, and they had a BMI of 23.4±4.4 and 23.8±4.7, respectively.
At PE, patients who went on to develop CTEPH were more likely to have unprovoked PE (79.2% vs 40.2%; P <.001), to present with hypoxemia (70.8% vs 44.0%; P <.001), they had higher right heart load (91.7% vs 40.5%; P <.001), and they had lower D-dimer levels (median, 6.0 vs 11.4 mg/mL; P <.001) compared with patients who did not develop CTEPH.
Most patients with CTEPH (97.9%) were diagnosed within 3 years of PE. A total of 7 patients with CTEPH died, due to malignant diseases (n=4), infection (n=1), chronic obstructive pulmonary disease (n=1), and unknown reasons (n=1). The survival rates after CTEPH were 95.7%, 93.5%, 88.4%, 85.0%, 85.0%, and 72.9% at years 1 through 6, respectively.
Risk for CTEPH was associated with right heart load (adjusted hazard ratio [aHR], 9.28; 95% CI, 3.19-27.00; P <.001), unprovoked PE (aHR, 2.77; 95% CI, 1.22-6.30; P =.02), hypoxemia (aHR, 2.52; 95% CI, 1.26-5.04; P =.009), female gender (aHR, 2.09; 1.05-4.14; P =.04), per day delay in diagnosis from symptom onset (aHR, 1.04; 95% CI, 1.01-1.07; P =.01), and D-dimer levels per 1 mg/mL (aHR, 0.96; 95% CI, 0.92-0.99; P =.02).
This study was limited by the lack of diversity in the study cohort, which may limit the generalizability of these findings.
The study authors concluded, "In this large real-world VTE registry in the DOAC [direct oral anticoagulation] era, the cumulative detection of CTEPH after acute PE was 2.3% at 3 years. Several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population for CTEPH after acute PE."
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors' disclosures.
This article originally appeared on The Cardiology Advisor
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