Current Projects

Chronic Severe Mitral Regurgitation and Atrial Fibrillation

Animal model of atrial fibrillation. A: Transthoracic echocardiogram (apical 4-chamber view) of mitral valve shows an eccentric regurgitant jet. B: 3D reconstruction of the mitral valve illustrates coaptation defect. C: Left atrial volume increases over 9 months after the creation of MR. (n=6).

Mitral regurgitation (MR) is the most common valvular disease in humans. Many MR patients later develop atrial fibrillation. To understand the underlying mechanisms, we developed an animal model of MR, based on avulsing some of the chordae that hold the mitral valve in place.

After chordae have been avulsed, MR can be demonstrated in a transthoracic echocardiogram (see Panel A), and the valve shows coaptation defect (Panel B). After MR creation, left atrial volume increased dramatically, by about 200% over 9.5 months.

We are now using this model of MR to understand the molecular mechanisms of atrial and ventricular remodeling with the goal of developing interventions to prevent atrial fibrillation and other secondary diseases.

We are also studying the effects of mitral regurgitation in patients referred for surgery with without atrial fibrillation. We are using novel, noninvasive imaging technology, in attempt to define the underlying substrate in atrial fibrillation. We hope to use this information in the future to guide surgical ablation.

Bipolar Radiofrequency Ablation

A single ablation with AtriCure’s Encompass clamp created a “Figure of 8” box lesion, (green arrow), on the endocardial surface of the left atrial posterior wall. There was no evidence of clot, charring, or pulmonary vein damage. RA = right atrium, LA = left atrium, PVs = Pulmonary veins.

An important treatment option for patients with atrial fibrillation is the ablation of cardiac tissue to create nonconducting lesions that disrupt the pathways of reentrant arrhythmias. In current clinical practice, cardiac ablation is performed thermally, either by heating tissue with radiofrequency currents or by freezing it with a cryogen. We are regularly testing new thermal ablation devices for their ability to create transmural lesions.

Nanosecond Pulsed Field Ablation of Cardiac Tissue

Nanosecond pulsed field ablation (nsPFA) of cardiac tissue. A: Section of atrial wall tissue showing a lesion (white) created with nsPFA. B: The lesion from (A) as a Gomori trichrome stain. C: Abrupt transition from surviving tissue (left) to ablated tissue (right). D: High-resolution GMT stain of nsPFA-ablated tissue.

Nanosecond pulsed field ablation (PFA) is an alternative to the thermal ablation methods described above. PFA is nonthermal and  relies on strong electric fields to disrupt cell membranes in order to ablate tissue. PFA can significantly reduce ablation times while providing excellent ablation depth. It also avoids thermal effects such as char buildup on the ablation clamp that can lead to incomplete lesions for radiofrequency ablation.

Optogenetics and Sonogenetics in the Heart

Experimental setup for ultrasound stimulation of Langendorff-perfused hearts. A: Photograph of a naïve heart in our ultrasound testing setup. B: Activation map that shows propagating cardiac activity following successful activation. Activation was initiated with an electrical stimulus, delivered via an electrode at the position marked “X” (ultrasound did not initiate electrical activity in naïve hearts).

The beating of the cardiomyocytes that make up the heart is synchronized by electrical signals that are generated by the sinus node and propagate over the heart. If the heart is genetically modified to include light-sensitive ion channels, activation can be achieved with a light (optogenetics). Similarly, adding ultrasound-sensitive ion channels allows stimulation with ultrasound (sonogenetics).

In collaboration with Drs. Chao Zhou, Jianmin Cui, and Hong Chen from the Department of Biomedical Engineering, we are developing murine models of optogenetics and sonogenetics in the heart, enhancing the options for non-invasive stimulation of the heart.