Vascular Cardiotoxicity of Ponatinib

Study Overview
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Brief Summary
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Pre-clinical studies suggest that the third generation tyrosine kinase inhibitor ponatinib can result in microvascular angiopathy and acceleration of atherosclerosis. This study is intended to examine for myocardial microvascular angiopathy and changes in carotid plaque in patients receiving ponatinib as part of their clinical care.

Detailed Description
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In this study, we will perform serial echocardiography for ventricular function, myocardial contrast echocardiography for microvascular perfusion assessment, blood analysis for myocardial injury, and carotid US for plaque or IMT progression in subjects receiving ponatinib. This series of tests is intended to provide information on the presence of clinically-evident or subclinical microvascular angiopathy and plaque acceleration.

Official Title
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Vascular Cardiotoxicity of Ponatinib

Conditions
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Cardiotoxicity

Intervention / Treatment
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* Diagnostic Test: Contrast ultrasound perfusion imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CML or ALL Prescribed ponatinib Exclusion Criteria: pregnancy or lactation major medical illness involving the heart or vasculature (CAD, PAD, DCM). hemodynamically unstable allergy to ultrasound contrast agents.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Contrast ultrasound perfusion imaging|Contrast ultrasound perfusion imaging for microvascular perfusion, and carotid ultrasound data on intima-media thickness (or plaque size) will be serially assessed in subjects started on ponatinib.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence versus absence of any myocardial perfusion defect assessed by visual analysis for any abnormalities of microvascular flux rate (beta function) or microvascular blood volume during an infusion of ultrasound microbubble contrast agents. | Contrast ultrasound perfusion imaging will be performed using power-modulation imaging and infusion of an ultrasound contrast agent. Destruction replenishment kinetics will be assessed visually by examination of delayed replenishment of signal intensity (>5 seconds) after a high-mechanical index burst sequence, or abnormalities in plateau intensity reflecting regional abnormalities in myocardial microvascular blood volume. | 6 months | 
| Presence versus absence of any myocardial perfusion defect assessed by visual analysis for any abnormalities of microvascular flux rate (beta function) or microvascular blood volume during an infusion of ultrasound microbubble contrast agents. | Contrast ultrasound perfusion imaging will be performed using power-modulation imaging and infusion of an ultrasound contrast agent. Destruction replenishment kinetics will be assessed visually by examination of delayed replenishment of signal intensity (>5 seconds) after a high-mechanical index burst sequence, or abnormalities in plateau intensity reflecting regional abnormalities in myocardial microvascular blood volume. | 12 months | 
| Carotid plaque size | Changes in IMT or plaque size | 6 months | 
| Carotid plaque size | Changes in IMT or plaque size | 12 months |