June 1, 2023 Medical Grand Rounds Recap

The Department of Internal Medicine Grand Rounds, “Absolute Chaos: Hurricanes, Butterflies and Fibrillation,” was presented on June 1 by Joseph G. Akar, MD, PhD, professor of medicine (cardiovascular medicine) and director of the Cardiac Electrophysiology Program and Complex Ablation Program.

First, Akar shared a story about two patients with a heart rhythm disorder called atrial fibrillation or AF, a condition associated with an increased risk of stroke, tachyarrhythmia, and heart failure. The patients were young adults with a slow heart rate. In fact, multiple family members had the same condition.

Akar worked with Arya Mani, MD, Robert W Berliner Professor of Internal Medicine (Cardiology) and professor of genetics, to collect DNA samples. The found a rare genetic mutation of phosphodiesterase-4D-interacting-protein or PDE4DIP that resulted in slow ventricular response.

The investigation was published in the journal Human Mutation.

Next, Akar described the mechanism for atrial fibrillation.

“Atrial fibrillation actually started with a spiral wave, with a single wave that was spinning very fast, and the tissue could not keep up with it. This is something that we see in real life. That’s what fibrillation essentially is: this hurricane that’s basically splintering into fibrillatory conduction,” said Akar.

“So that begs the question then: why is it that two patients who are brothers with atrial fibrillation get two seemingly very, very different atrial fibrillation procedures? Because I told you what the mainstay of ablation is. And the short answer is because pulmonary vein isolation (PVI) works really well for patients with atrial fibrillation, but it’s actually fairly poor to control persistent atrial fibrillation. So PVI alone —isolation of the veins— is not enough for persistent atrial fibrillation.”

To understand the real-world outcomes of patients undergoing AF ablation procedures Akar along with Yale’s Center for Outcomes Research and Evaluation (CORE), Jeptha Curtis, MD, James V. Freeman MD, MPH, MS, and colleagues from the University of California-San Diego used data from the American College of Cardiology Atrial Fibrillation Ablation Registry. They discovered that patients with persistent atrial fibrillation were more likely to experience post-procedural complications depending on what set of ablation lesions they received. The findings were published in the Journal of the American College of Cardiology.

Akar explained, “What we believe here at Yale is that the question that was being asked is actually the wrong question, and that’s why we keep getting the wrong answer. The more appropriate question is how to determine which AF signals represent active rotors that are driving fibrillation. The challenge is that AF signals are highly complex and non-linear. They are not random but are chaotic and display high sensitivity to initial conditions where very small changes result in very large differences: a butterfly flapping its wings in Brazil results in a tornado in Texas.” Akar and his colleagues James Hummel, MD, and Fadi Akar, PhD, use a combination of computer modeling, optical mapping and a non-linear signal analytic approach called RQA or Recurrence Quantitative Analysis to help understand these complex signals.

1. Is there anything peculiar about atrial fibrillation?
2. What is the mechanism of AF?
3. How can we improve ablation of persistent AF?
   1. Identify the best site for ablation
   2. What is the best approach to ablating that site?
   3. How can we monitor the effect of ablation at that site?
4. Could the stroke have been prevented?

To learn more about electrophysiology research at Yale, visit Electrophysiology. Yale faculty and staff can review videos of Medical Grand Rounds.