ASE Funded Research – Project Summaries
Mohamed Ahmed, David Schwartzman, John Gorcsan. University of Pittsburgh, Pittsburgh, PA
Shahryar M. Chowdhury, Girish Shirali, George Hamilton Baker, Paul Nietert, Anthony Hlavacek. Medical University of South Carolina, Charleston, SC
Specific Aim # 2: Assess the application and provide reference values for these same non-invasive indices in a large cross-sectional pediatric/CHD population.
There will be two arms to this study, 1) validation arm and 2) outpatient arm. In the validation arm, patients with biventricular anatomy undergoing retrograde left heart catheterization in the pediatric catheterization laboratory will be enrolled prospectively to have PVL analysis of the left ventricle. Measures of correlation between invasive and non-invasive measures of contractility will then be calculated. We estimate 30 subjects in this arm with subgroup of 10 patients with left sided obstructive lesions. The second, outpatient arm of patients will be recruited prospectively from our pediatric cardiology outpatient clinic. All patients with a normal echocardiogram will be approached for enrollment. We expect to enroll a minimum of 200 patients into this arm. We will propose reference values based on these results and assess for inter- and intra-observer variability.
The ideal tool for measuring myocardial contractility in children would be non-invasive, quick, load independent, with low intra- and inter-observer variability, and be validated invasively in children against the gold standard. The indices examined in the proposed study have the potential to meet these criteria and could be moved from the laboratory to the bedside. Applying these newly validated measures could significantly advance our ability to understand the effects of pharmacologic, catheter, and surgical interventions on ventricular mechanics in pediatric cardiology.
Charlie E. Luoma1, Monique A. Freund1, Larry C. Casey1, Hector R. Villarraga2. 1Mayo Clinic Health System – Franciscan Healthcare, La Crosse, WI;2Mayo Clinic, Rochester, MN
Benjamin Freed, Mardi Gomberg-Maitland, Victor Mor-Avi, Amit Patel, Roberto Lang. University of Chicago Medical Center, Chicago, ILProject summary: Despite the advent of multiple new therapies in the last decade, approximately 15% of patients with pulmonary arterial hypertension (PAH) will die in one year. Contemporary prognostic scores, which include a variety of independent predictors of survival, attempt to risk stratify these patients so that the proper treatment can be given at the appropriate time. Since the right heart plays an integral part in the disease process of PAH, its structure and/or function may provide potential prognostic information. However, because the right heart is particularly challenging to assess with two-dimensional echocardiography (2DE), the only imaging parameter included in these scores is the presence of pericardial effusion.
In 2010, the American Society of Echocardiography (ASE) published guidelines for the optimal assessment of the right heart using a variety of 2DE parameters. While some of these parameters provide prognostic information in patients with PAH, there is no direct comparison between all recommended variables for assessing the right heart. Although real-time three dimensional echocardiography (RT3DE) and cardiovascular magnetic resonance (CMR) have proven to be more accurate and reproducible in measuring the right ventricle than 2DE, little data exists as to their role in predicting outcomes in patients with PAH. We, therefore, hypothesize that direct, three dimensional measurements of right ventricular size and function, such as those provided by RT3DE and CMR, will provide the most powerful independent imaging-based predictors of poor outcomes.
This study aims to test this hypothesis by prospectively enrolling patients with PAH to undergo 1) a comprehensive 2DE and RT3DE evaluation; 2) a CMR study; 3) laboratory tests including creatinine and NT-proBNP; and 4) a six minute walk test within a 24-hour time frame. Patients will be tracked monthly for the occurrence of the primary endpoint of time to clinical worsening (all-cause mortality, PAH-related hospitalization, and lung transplantation). The reproducibility and prognostic capability of all ASE-recommended 2DE parameters will be compared to those of RT3DE and CMR right ventricular measurements in order to determine which imaging modality is best at providing independent predictors of poor outcomes in this patient population. The significance of our study is that it provides a necessary step to showing that cardiovascular imaging provides important prognostic data in patients with PAH that will enhance the already established non-imaging data and help in improving patient outcomes.
The use of strain techniques and 3D echocardiography in the diagnosis of subclinical cardiotoxicity in breast cancer patients following treatment with anthracycline and trastuzumab chemotherapy
Timothy Tan, Michael Picard, Marielle Scherrer-Crosbie. Massachusetts General Hospital, Boston, MA
Project summary: Left ventricular (LV) dysfunction is a major limitation of breast cancer treatments. Echocardiography is used to monitor cardiac function in chemotherapy-treated patients, however, conventional approaches currently used such as LV ejection fraction may not detect early LV dysfunction. Recently, myocardial strain and strain rate measured using tissue Doppler imaging (TDI) have been shown to be sensitive markers of LV function in cardiac pathologies. Strain rate in particular appears to accurately reflect myocardial contractility. The role of these parameters in the follow-up of patients treated by chemotherapy has not been investigated and will be explored in this research proposal.
Our group has validated 2D strain echocardiographic indices in an animal model of chemotherapy-induced cardiotoxicity. While 2D strain and strain rate assessments provide better sensitivities in the detection of subclinical LV dysfunction post chemotherapy compared to conventional echocardiographic techniques, it is still hampered by the limitations associated with imaging within a 2 dimensional plane. We propose that the utilization of 3D strain and strain rate assessments would significantly improve the sensitivities in the detection and assessment of subclinical cardiac dysfunction in individuals prior to and post chemotherapy.
We will study patients with HER2 positive breast cancer treated with anthracyclines and tratsuzumab. The first aim of this proposal is to detect subclinical LV dysfunction earlier than conventional parameters. The second aim is to identify patients at high-risk for heart failure prior to chemotherapy treatment.
We propose the following hypotheses: 1) Myocardial strain and strain rates will differ significantly pre and post treatment with chemotherapy. Myocardial deformation patterns are also likely to reach lower peak values or demonstrate significant changes following chemotherapy. 2) Myocardial strain and strain rates will be reduced in individuals with other pre-existent cardiac comorbidities which would place them at increased risk of developing cardiotoxicity if treated with known cardiotoxic chemotherapeutic agents such as anthracyclines or trastuzumab. Women who can be identified as being at high risk of cardiac toxicity, or who begin to show early signs of it, could be treated with alternative chemotherapy regimens and may benefit from increased cardiac monitoring or preventive cardiac treatments. The development and validation of 3D strain echocardiography protocol in this setting would provide us with an invaluable noninvasive diagnostic tool to allow us to characterize the patients most susceptible to developing chemotherapy-induced cardiotoxicity and to increase our understanding of heart failure associated with cancer treatment potentially helping to decrease its morbidity and mortality.
Rory Weiner, Michael Picard, Aaron Baggish. Massachusetts General Hospital, Boston, MA
Our group has recently developed novel techniques for the standardization of LVT and untwisting rate (UTR) imaging using STE and has begun to apply this to clinically relevant questions. In the current proposal we aim to apply these techniques to measure LVT and UTR in healthy individuals and in subjects with clinically relevant forms of left ventricular hypertrophy (LVH), including hypertrophic cardiomyopathy (HCM), hypertensive LVH, and exercise-induced LVH. Assessment of LVT and UTR will be performed under resting conditions and during exposure to the cardinal hemodynamic stresses of volume (large volume normal saline infusion) and pressure (isometric hand grip testing).
We propose the following hypotheses: 1) LVT and UTR will differ significantly between healthy individuals and those with LVH; 2) LVT and UTR will differ significantly across the different etiologies of LVH; 3) LVT and UTR will both demonstrate significant load dependence and the magnitude of this load dependence will be a function of LV geometry. As such, the proposed work has the potential to advance the study of LVT and UTR by utilizing STE with torsion-specific imaging criteria to define reference values in healthy individuals as well as subjects with common clinical forms of LVH. Furthermore, assessment of changes in LVT and UTR with volume and pressure challenges will clarify the degree of load dependency of LV twist mechanics in these different subject populations. Results from this work will facilitate the clinical application of STE-derived LVT and UTR measurements.
Ben Lin, Albert Sinusas. Yale University, New Haven, CT
Project summary: Left ventricular (LV) remodeling after myocardial infarction (MI) is a leading cause of the development of chronic heart failure. Transmural myocardial injury is correlated with higher rates of pathologic LV remodeling than non-transmural injury. Echocardiographic myocardial strain and strain rate imaging have been used to determine the extent of MI, but there is limited information related to using these parameters to predict LV remodeling after acute MI.
Intracavitary vortical flow patterns have been shown to be altered in diseased hearts during LV filling and may be associated with decreased cardiac pumping efficiency. However, little is known about temporal changes in intracavitary flow patterns in relation to changes in regional myocardial strain or LV remodeling.
Using echocardiography in chronic canine models of transmural and non-transmural MIs, we propose studies with the following specific aims:
1. Test the hypotheses that early regional myocardial strain measurements after MI are related to infarct transmurality and are predictive of late LV remodeling. These hypotheses will be tested by comparing estimates of radial, circumferential and longitudinal strains from 2D speckle tracking with serial changes in LV geometry.
2. Test the hypotheses that intracavitary vortical flow patterns after MI are related to infarct transmurality and are predictive of late LV remodeling. We will compare 2D Doppler and contrast speckle tracking measurements of velocities and vorticity parameters (including circulation, sphericity index and vortex formation time) with serial changes in LV geometry.
3. Determine if combining measurements of regional myocardial strain and vortical flow dynamics after MI provides any incremental value in predicting LV remodeling.
Significance: These studies aim to determine the relevance of biomechanical parameters related to strain and blood flow for early prediction of the occurrence of pathologic LV remodeling.