Left ventricular ejection fraction, or LVEF, is the percentage of blood the left ventricle pumps out with each contraction, and it remains the workhorse metric of cardiac function worldwide. In the transplant arena, most research attention has focused on the donor heart’s LVEF at the time of procurement. Curiously, that early measurement has proven surprisingly uninformative: donor hearts with impaired function at procurement often recover fully, a phenomenon attributed in part to the catecholamine surge that follows donor brain death, which can temporarily stun the ventricle. When ischemic time is kept under four hours, recipients of such hearts generally fare well. What has been far less clear is whether the LVEF recorded a year after transplantation, once the dust of surgery has settled, carries any prognostic weight.

To answer that question, researchers led by Ahad Firoz of the University of California, Davis Medical Center, together with colleagues at UC Davis and the Lewis Katz School of Medicine at Temple University, analyzed adult first-time isolated orthotopic heart transplant recipients transplanted between January 2010 and September 2022 who survived to their one-year follow-up. Recipients with missing LVEF data at that visit were excluded, leaving a final cohort of 23,629 patients. The investigators deliberately chose the one-year mark because ventricular dysfunction related to procurement injury and acute postoperative graft changes is expected to have resolved by then, making any residual dysfunction a meaningful signal rather than a transient artifact. Follow-up data collected between 0.75 and 1.25 years after transplant were used, and patients were tracked until October 2023.

The cohort was stratified into four clinically grounded categories: preserved LVEF of 50 percent or above, which served as the reference group and comprised 96.4 percent of recipients; mildly reduced LVEF of 40 to 49 percent; moderately reduced LVEF of 30 to 39 percent; and severely reduced LVEF below 30 percent. Mean LVEF values in these groups were 61.1, 44.3, 34.3, and 21.6 percent respectively. The statistical architecture of the study was deliberately conservative. Four sequential models adjusted for an expanding set of covariables, culminating in a fully adjusted model that accounted for recipient demographics, functional status, comorbidities such as diabetes and hepatitis C, rejection episodes, hospitalizations, dialysis requirement, and an extensive panel of donor characteristics including donor LVEF at procurement, ischemic time, donor-recipient predicted heart mass ratio, and HLA-DR and CMV mismatch.

The headline result was a graded, dose-response relationship between one-year LVEF and mortality. Across 1,802 deaths recorded during follow-up, three-year survival from the baseline exam fell from 91.0 percent in the preserved group to 84.7 percent with mildly reduced, 74.3 percent with moderately reduced, and 68.5 percent with severely reduced function. In the fully adjusted Cox regression models, mildly reduced LVEF carried a 28 percent higher hazard of all-cause mortality (hazard ratio 1.28, p = 0.011), moderately reduced LVEF a 90 percent higher hazard (HR 1.90, p < 0.001), and severely reduced LVEF more than double the hazard (HR 2.06, p = 0.002). Cardiovascular mortality followed an even steeper gradient, with hazard ratios of 1.98, 3.17, and 4.54 across the three reduced categories, meaning patients with severely reduced function faced a 354 percent greater risk of dying from cardiovascular causes than those with preserved function.

Beyond survival, the study broke new methodological ground by applying a competing-risk framework to cardiac allograft vasculopathy, the progressive, atherosclerosis-like narrowing of the transplanted heart’s coronary arteries that is among the most feared late complications of transplantation. Using cumulative incidence functions, Gray’s test, and Fine-Gray subdistribution hazard models, with death treated as a competing event, the team found that the median time to CAV after the first annual visit shrank progressively as LVEF declined, from 2.9 years in the preserved group to just 1.2 years in the severely reduced group. After full adjustment, the subdistribution hazard ratios for CAV were 1.28, 1.57, and 1.65 for the mildly, moderately, and severely reduced groups respectively. This is the first report in the literature to assess CAV outcomes across LVEF groups using a competing-risk model, an approach that guards against overestimating risk when many patients die before vasculopathy can develop.

The web of associated morbidity extended well beyond the arteries. Recipients with reduced one-year LVEF experienced higher rates of hospitalization during follow-up, more frequent acute allograft rejection requiring treatment, and greater incidence of both early postoperative kidney injury necessitating dialysis and chronic kidney failure requiring dialysis. New-onset diabetes after transplantation was also more common, affecting 9.7 percent of recipients with reduced LVEF compared with 6.7 percent of those with preserved function. At the two-year follow-up, the differences persisted or widened: only 37.8 percent of patients who had severely reduced LVEF at one year retained preserved function at two years, compared with 97.4 percent of the preserved group, and re-transplantation rates climbed from 1.0 percent in the preserved group to 8.2 percent in the severely reduced group.

The authors propose a plausible biological narrative linking these findings, while cautioning that causality cannot be established from retrospective registry data. Maladaptive processes that predispose the allograft to dysfunction may begin early after surgery, triggering a cascade: reduced cardiac output diminishes renal perfusion, fostering a cardiorenal-like syndrome and dysregulation of the renin-angiotensin-aldosterone system; rejection episodes prompt escalating doses of nephrotoxic immunosuppressants, further injuring the kidneys and promoting new-onset diabetes; and chronic or recurrent rejection, particularly the poorly understood antibody-mediated form, drives the progression from acute graft dysfunction to vasculopathy. Each of these complications, in turn, is independently associated with mortality, which may partly explain the striking survival gradient observed. Consistent with this, functional status at one year and rejection within the first year were the strongest predictors of reduced LVEF in the study’s regression analyses.

The study has limitations inherent to its design. As a retrospective registry analysis, it cannot establish temporal sequence, and the granularity of OPTN data is constrained: the circumstances under which the one-year echocardiogram was obtained, whether routine screening or diagnostic work-up, are unknown, raising the theoretical possibility of ascertainment bias, which the authors mitigated by anchoring measurements to a strict window around the annual visit. Information on CAV severity was also unavailable beyond its presence. Nevertheless, the sheer scale and diversity of the cohort, spanning multiple centers across the United States in the modern era of transplantation, lend the findings considerable generalizability, and the study is by far the largest investigation to date of one-year LVEF after heart transplantation.

The clinical message is straightforward and potentially practice-changing. A single echocardiographic number obtained at the one-year visit, a test many centers already perform, appears to identify a high-risk minority of recipients who warrant intensified surveillance: screening for vasculopathy, close monitoring of renal function and glucose metabolism, vigilance for rejection, and timely escalation of therapy. Because advanced CAV has limited treatment options and re-transplantation carries substantial risk, early identification of patients on that trajectory could mean the difference between intervention while the graft is still salvageable and crisis management after irreversible decline. For the roughly one in twenty-five transplant recipients whose graft function has not normalized by the first anniversary, that routine ultrasound image may now be recognized as far more than a formality; it may be a forecast.

Subject of Research: Prognostic value of one-year left ventricular ejection fraction after heart transplantation

Article Title: Prognostic implications of one-year left ventricular systolic function after heart transplantation

Article References: Firoz, A., Ebong, I., Cadeiras, M., Zhao, H., & Jimenez, S. (2026). Prognostic implications of one-year left ventricular systolic function after heart transplantation. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03022-1

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03022-1

Keywords: heart transplantation, left ventricular ejection fraction, cardiac allograft vasculopathy, graft rejection, mortality, OPTN registry, echocardiography, renal failure, prognosis, survival, immunosuppression, cardiology