Multimodal Evaluations May Flag Cardiac Allograft Problems Earlier

Coronary anatomy and physiology both predicted early cardiac allograft vasculopathy (CAV) progression, according to a study that strengthens the case for advanced multimodal testing to improve early detection of a major contributor to allograft failure.

Among heart transplant recipients at two Canadian centers, early progression of percent intimal volume (PIV) on intravascular ultrasound (IVUS) between baseline and 12 months was independently predicted by recipient male sex, fibrotic plaque on optical coherence tomography (OCT), and the index of microcirculatory resistance (IMR), found Sharon Chih, MBBS, PhD, a transplant cardiologist at the University of Ottawa Heart Institute in Ontario, and colleagues.

"This is the first study to prospectively examine the development of CAV in the first year of HT [heart transplantation] by combining serial high-resolution OCT imaging and intracoronary physiology assessment," the authors noted of their paper, published in Circulation: Heart Failure.

Aside from contributing to understanding of early CAV development, the findings "solidify the importance of OCT and coronary physiology assessment for early CAV detection and risk stratification," Chih and colleagues wrote.

If larger multicenter studies show that an OCT- and IMR-directed personalized management strategy improves patient outcomes, higher-risk individuals might be identified in the future and provided early treatment and close invasive surveillance, they suggested.

Chih's group noted that, for now, invasive coronary angiography (ICA) remains the recommended clinical standard for evaluating CAV, a leading and hard-to-predict cause of late mortality and allograft failure after heart transplantation. CAV often only manifests late in its course with major cardiac events, leaving a need for early detection when there is still a chance to halt disease progression.

"Ultimately, no matter how sophisticated are strategies for prediction of CAV progression, they are only of value if matched by equally sophisticated strategies for CAV treatment and prevention," according to Kelly Schlendorf, MD, MHS, a transplant cardiologist at Vanderbilt University Medical Center in Nashville, Tennessee.

"Despite treatment with statins and proliferation signal inhibitors, both demonstrated to reduce CAV progression, many patients exhibit worsening disease, highlighting the need for better and more personalized therapies," Schlendorf wrote in an accompanying editorial.

The ECAV study comprised consecutive heart transplant recipients at two centers, one in Toronto and the other in Ottawa. Excluding individuals who died within 3 months of transplant or had contraindications to invasive coronary evaluation, there were 82 people enrolled in 2018-2021.

The cohort averaged 51 years of age, with 60% men. The most common indications for transplant were dilated cardiomyopathy (28%) and ischemic cardiomyopathy (23%).

All participants underwent prospective evaluation 3 and 12-month posttransplant with angiography and left anterior descending artery IVUS, OCT, fractional flow reserve, coronary flow reserve, and IMR measurements.

In the 12 months after heart transplant, OCT measurements of vessel size worsened: median intimal volume grew by 42%, percentage intimal volume increased by 44%, and lumen volume shrank 9%. "Significant coronary disease progression occurs in the first year of HT and is associated with intimal plaque expansion, negative remodeling, and luminal reduction," Chih and colleagues reported.

Donor atherosclerosis (defined as baseline IVUS maximal intimal thickness ≥0.5 mm) had been evident in half of participants at baseline.

De novo CAV with a maximal intimal thickness of ≥0.5 mm on follow-up was observed in 24%, while rapidly progressive CAV (maximal intimal thickness ≥0.5-mm increase from baseline) was reported in 13%.

The proportion of people with abnormal coronary physiology rose from 41% at baseline to 45% at 1 year. One in five had microvascular dysfunction (IMR ≥25).

The observational study was limited by its small sample size and inability to control for unmeasured confounding, study authors acknowledged.

Notably, Schlendorf added, excluding patients with severe renal dysfunction or difficult vascular access introduced potential selection bias.

"Despite these limitations, however, and unlike other mostly unimodal studies in this space, the ECAV study elegantly lays the groundwork for multimodal coronary interrogation in HT recipients and highlights the disappointing reality that as much as is understood about the pathogenesis of CAV, there is just as much that is yet to be understood," she maintained.

The editorialist stressed that the "ECAV study underscores the importance of coupling structure with function and raises the possibility that physiologic changes in coronary flow may be as or more important."

To improve long-term survival after heart transplantation, studies on comprehensive, multimodal coronary assessments, their relative significance in individual patients and their treatment implications are needed, she added.

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