Prediction of Cardiac Allograft Vasculopathy Progression 1-Year Posttransplant

In the first year following heart transplantation, cardiac allograft vasculopathy (CAV) progression can be predicted via index of microcirculatory resistance early posttransplant and fibrotic plaque on optical coherence tomography, according to findings published in Circulation: Heart Failure.

Investigators sought to assess predictors of early CAV progression by characterizing first-year posttransplant anatomic-physiologic changes in the coronary vasculature.

They conducted a prospective study (ClinicalTrials.gov Identifier: NCT03217786) from January 2018 to March 2021 at the University of Ottawa Heart Institute, Ottawa, Canada, and the University Health Network, Toronto, Canada. The study included 82 adult heart transplant (HT) patients (mean age, 51 years; 40% women). Participants received index microcirculatory resistance measurements, coronary flow reserve measurements, fractional flow reserve measurements, optical coherence tomography, angiography, and left anterior descending artery intravascular ultrasound prospective assessment at 3 months (mean 13.8 weeks posttransplant) and 12 months (mean 56.3 weeks) posttransplant.

Intravascular ultrasound change in percentage intimal volume from baseline to 12-month follow-up was used to evaluate CAV progression. Most common indications for transplant were ischemic cardiomyopathy (23%) and dilated cardiomyopathy (28%). Patients with difficult arterial vascular access, allergy to iodinated contrast, contraindications to invasive coronary evaluation, or who died within 3 months of transplant were excluded.

The investigators found that in 50% of patients, donor atherosclerosis (baseline intravascular ultrasound maximal intimal thickness, ≥0.5 mm) was present. Rapidly progressive CAV (maximal intimal thickness, ≥0.5-mm increase from baseline) developed in 13% of patients. De novo CAV (follow-up maximal intimal thickness, ≥0.5mm) developed in 24% of patients.

Lumen volume decreased 9% (-1.02 mm³/mm), vessel volume decreased 4% (-0.50 mm³/mm), percentage intimal volume increased 44% (4.6%), and baseline to follow-up median intimal volume increased 42% (0.58 mm³/mm) on optical coherence tomography. Between baseline and follow-up, there was no significant change in median coronary flow reserve, index of microcirculatory resistance, or fractional flow reserve.

At baseline angiographic disease was found in 11% of patients and, at follow-up, in 22% of patients. Investigators noted 18% median maximum vessel stenosis at baseline and 21% at follow-up. Between the 3 major coronary artery territories, they found no significant difference in disease progression (P =.52).

Predominant morphology was fibrotic plaque (baseline, 29%; follow-up, 50%). One in 5 patients had microvascular dysfunction (index of microcirculatory resistance, ≥25), with 41% of patients at baseline and 45% at follow-up with abnormal coronary physiology. Independent predictors of coronary disease progression included index of microcirculatory resistance, fibrotic plaque, and recipient male sex on multivariable linear regression analysis.

Study limitations include the underpowered sample size, and that baseline assessment at 3 months does not compare with baseline in most other posttransplant studies. The intracoronary assessment is only in the left anterior descending artery, and the follow-up range is too short.

“Fibrotic plaque on optical coherence tomography and index of microcirculatory resistance early posttransplant predict CAV progression in the first year of transplantation,” the investigators wrote. “Serial intracoronary imaging and physiologic assessment in the first year of heart transplantation demonstrate proportionally greater intimal plaque expansion than vessel constriction and lumen reduction, predominant fibrotic plaque morphology, and microvascular dysfunction affecting 1 in 5 patients.” The investigators believe that following heart transplantation, patients with microvascular dysfunction and fibrotic plaque at risk of early cardiac allograft vasculopathy progression can be identified with early examination using measurement of index of  microcirculatory resistance and optical coherence tomography.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.