Post-myocardial Infarction Edema Follows A Bimodal Pattern

The response of the human heart to an infarction is very different than previously thought, collaborative research has demonstrated. The study, led by cardiologist Borja Ibáñez, overturns the established view that an infarction is followed by progressive repair of the myocardium.

For many years, scientists have assumed that a heart attack is followed immediately by an inflammatory response featuring increases in water content and cellular infiltration, and that this response remains stable for at least one before progressively dissipating.

Two years ago, the research team behind the new studies published a series of animal studies that challenged this view, but the most important challenge remained: to validate the new findings in human patients.

The new studies used MRI technology to demonstrate that the human heart produces two well-differentiated edematous reactions occurring at distinct times after an infarction. These results have immediate clinical implications for ongoing clinical trials and could form the basis of future studies focused on the specific modulation of each of these independent edematous phases.

Myocardium Reaction Questions

The project came out of research started more than 10 years ago at Mount Sinai Hospital in New York, directed by renowned cardiologist Valentín Fuster, an author on both of the new CNIC-led studies. Rodrigo Fernández-Jiménez, first author on both studies, said,

“Surprisingly, we still know very little about how the myocardium reacts to an infarction, and it is only through the use of MRI, which allows noninvasive, millimeter-resolution mapping of tissue composition that we are beginning to understand many of its mysteries.”

The bimodal postinfarction inflammatory reaction was first demonstrated in animals in 2015, but this left the much more difficult challenge of demonstrating that the same phenomenon occurs in humans.

Undertaking such a study required a special setup that would allow detailed MRI studies to be carried out immediately after the re-establishment of blood flow through the blocked coronary artery in heart attack patients. This requires highly complex technology and is therefore possible in only a handful of centers.

One center with the technology and expertise to carry out this type of study is the university hospital in Salamanca. Chief cardiologist Pedro Luis Sánchez said,

“We’ve been able to carry out this work thanks to the enthusiasm and commitment of everyone in the service. Heart attacks can happen at any time of day or night, and for this study, we needed to do the first MRI scan within three hours of fitting a stent in the blocked artery to re-establish blood flow. Patients are particularly vulnerable during this period, so in addition to the expert MRI specialists, we also needed a full clinical support team on hand to provide continuous care during the examination period.”

Human Bimodal Inflammatory Response

The study is the first in the world to study heart attack patients via MRI so soon after the re-establishment of blood flow. In addition to studies in patients, the team has also extended the investigation to infarction in pigs, the experimental model most similar to humans.

Dr. Fernández-Jiménez said:

“MRI provides an extraordinary ability to noninvasively visualize events occurring after an infarction in real time, including inflammation, tissue volume expansion, hemorrhage, and obstruction of the microcirculation.”

According to Dr. Ibáñez, the discovery of the bimodal inflammatory response in the human heart:

“forces us to think about the best timing for MRI scans used in clinical trials to quantify irreversible injury and to monitor the effectiveness of interventions to reduce this injury. Until now, this question was not considered important, and cardiac imaging studies have been conducted on any day in the postinfarction period. The new findings show that the optimal time for these scans is between postinfarction days four and seven, when the second inflammatory/edematous wave is prominent and affects the entire region that was shut off from the blood supply during the infarction.”

Rodrigo Fernández-Jiménez, Manuel Barreiro-Pérez, Ana Martin-García, Javier Sánchez-González, Jaume Agüero, Carlos Galán-Arriola, Jaime García-Prieto, Elena Díaz-Pelaez, Pedro Vara, Irene Martinez, Ivan Zamarro, Beatriz Garde, Javier Sanz, Valentin Fuster, Pedro L. Sánchez and Borja Ibanez
Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage
Circulation 2017; CIRCULATIONAHA.116.025582

Image: CNIC