The renin-angiotensin-aldosterone system, or RAAS, is a peptidergic cascade with angiotensin II as its key effector. In healthy physiology it regulates blood pressure and fluid balance. In heart failure, reduced cardiac output, arterial underfilling and direct renal sympathetic stimulation push the system into overdrive, and the consequences are destructive: vasoconstriction, oxidative stress, inflammation, fibrosis of the heart and vasculature, and amplification of sympathetic nervous activity. Blocking this cascade with ACE inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists is a cornerstone of modern heart failure therapy. Yet guidelines do not routinely recommend these drugs after heart transplantation, and the question of whether the hormonal storm actually resolves once hemodynamics are corrected has remained largely unanswered.

To find out, the Vienna team enrolled patients with end-stage heart failure who were undergoing either heart transplantation or implantation of a left ventricular assist device, or LVAD, into a prospective registry. In total, 49 transplant recipients and 12 LVAD recipients were followed, with blood sampling shortly before and approximately six months after the intervention. The investigators measured NT-proBNP, the widely used marker of cardiac stress, plasma active renin concentration, aldosterone, and crucially the complete profile of circulating angiotensin peptides. Blood was drawn into tubes containing an inhibitor cocktail that instantly freezes angiotensin metabolism, allowing the researchers to capture a faithful snapshot, or fingerprint, of the circulating RAS at the moment of sampling.

The fingerprinting technique itself is a technical tour de force. Plasma samples were spiked with stable isotope-labeled internal standards for ten different angiotensin metabolites, then analyzed by liquid chromatography tandem mass spectrometry after solid-phase extraction. Because renin-dependent generation of angiotensin I is the rate-limiting step of the cascade, and ACE converts angiotensin I into angiotensin II, the relative abundance of downstream peptides such as angiotensin 1-7, angiotensin 1-5, angiotensin III and angiotensin IV reveals both the magnitude of systemic RAS activation and the mode of any pharmacological blockade. The sum of angiotensin I and angiotensin II served as a measure of the angiotensin burden carried by the classical RAS axis.

The results were unambiguous. After heart transplantation, the use of RAS inhibitors dropped significantly, as beta-blocker use fell from 63 to 2 percent and mineralocorticoid antagonist use collapsed from 55 to 8 percent, reflecting the standard de-escalation of heart failure drugs after transplant. In LVAD patients, by contrast, neurohormonal therapy remained broadly comparable before and after implantation, consistent with the strategy of continuing medication to promote reverse remodeling and myocardial recovery. Both interventions produced marked improvements in the visible signs of neurohumoral dysregulation. NT-proBNP fell from a median of 3015 to 1140 pg/mL after transplantation and from 8980 to 1836 pg/mL after LVAD implantation, while active renin concentration declined from 278 to 87 µIU/mL and from 847 to 131 µIU/mL respectively.

But the improvement stopped well short of normal. Not a single patient achieved normal NT-proBNP values after either intervention, and only 24 percent of transplant recipients and 33 percent of LVAD recipients reached normal renin levels. Plasma renin remained elevated in 76 percent of heart transplant patients and 67 percent of LVAD recipients, and in those patients clearly measurable angiotensin II persisted in the circulation. The angiotensin burden of the classical axis fell substantially after transplantation, from a median of 159 to 47 ng/L, and dropped numerically in the LVAD group from 214 to 42 ng/L, but it did not vanish. Aldosterone concentrations, notably, showed no significant change after either procedure. A tight correlation between renin and the combined angiotensin I plus angiotensin II levels, with a Spearman coefficient of 0.87, confirmed that renin remains the rate-limiting driver of the circulating cascade even after hemodynamic rescue.

Why does the hormonal system refuse to reset? The authors suggest a combination of mechanisms. In transplant recipients, persistent natriuretic peptide elevation has been attributed to cardiac denervation, immunosuppressive therapy, ventriculo-vascular uncoupling, endothelial dysfunction and subclinical allograft rejection. Prior studies have shown that natriuretic peptide levels peak within months of transplantation and decline gradually, but rarely normalize even years later; importantly, a late rise in NT-proBNP correlates strongly with allograft rejection, making these biomarkers clinically meaningful rather than mere curiosities. In LVAD patients, the picture is complicated by the devices themselves. Continuous-flow pumps may fail to stimulate arterial baroreceptors the way pulsatile flow does, potentially desensitizing receptors and raising intrinsic sympathetic tone, which in turn drives RAAS activation. Non-pulsatile kidney perfusion may independently activate the system, and preclinical work has linked continuous flow to impaired endothelial function, renal cortical artery hypertrophy and inflammatory infiltration.

The clinical implications are considerable. Ongoing angiotensin II spill-over is not a benign biochemical footnote: the peptide promotes the very processes, remodeling, fibrosis, inflammation and vascular dysfunction, that produce complications such as right ventricular failure in LVAD patients and possibly graft injury in transplant recipients. The study’s findings support a rationale for cardioprotective treatment, particularly with RAS inhibitors, in most patients after both transplantation and LVAD implantation, even though current transplant guidelines do not routinely recommend these agents. The Vienna group cautions, however, that this remains a hypothesis in this population. The impact of RAS inhibition specifically after transplantation and mechanical support should be tested in dedicated studies, and the long-term consequences of such a strategy, including interactions with immunosuppression and renal function, need careful evaluation.

Beyond its immediate therapeutic message, the study offers a conceptual shift. It reframes advanced heart failure not simply as a pumping problem that surgery can fix, but as a systemic neurohormonal disease whose imprint survives the replacement of the organ that caused it. The angiotensin fingerprints captured by mass spectrometry provide a new window into individual RAS regulation, showing exactly how pharmacological blockade reshapes the peptide landscape and where activation persists. For the growing population of patients living with transplanted hearts or mechanical circulatory support, the message is that the endocrine apparatus retains a memory of the failure it once served, and that memory may be a modifiable target for improving long-term outcomes.

Subject of Research: Persistent renin-angiotensin system activation and neurohormonal memory after heart transplantation or LVAD implantation in end-stage heart failure patients

Article Title: Memory of the renin-angiotensin system following heart transplantation or implantation of a left ventricular assist device

Article References: Memory of the renin-angiotensin system following heart transplantation or implantation of a left ventricular assist device. (n.d.). https://doi.org/10.1007/s00392-026-03018-x

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03018-x

Keywords: heart failure, heart transplantation, LVAD, renin-angiotensin system, angiotensin II, NT-proBNP, neurohormonal activation, mass spectrometry, cardiac remodeling, RAS inhibitors, aldosterone, plasma renin

The clinical story began long before the emergency that defined it. The boy was born at full term with a normal birth weight of 2608 grams, but by two months of age he was hospitalized for poor weight gain and declining cardiac function. Oral medications stabilized him enough for discharge after a two-month stay. Genetic testing eventually revealed a nonsense mutation, designated c.153C > G, in the TAZ gene, the molecular signature of Barth syndrome. This X-linked recessive condition arises from defects in an enzyme that remodels cardiolipin, a phospholipid essential to the structure and function of mitochondria, the energy-producing structures inside cells. The result is a constellation of problems: dilated cardiomyopathy in which the heart muscle stretches and weakens, generalized muscular hypotonia, and cyclical neutropenia that leaves patients vulnerable to infection. When the child was readmitted at one year of age with severe cardiac dysfunction and a brain natriuretic peptide level of 2096 pg/mL, a marker of profound heart strain, inotropic drugs failed to rescue him and he was transferred to Osaka for transplant registration and placement of a Berlin Heart EXCOR, the only durable ventricular assist device approved for small children in Japan.

His condition deteriorated faster than the transplant system could move. On admission he weighed just 6.1 kilograms and measured 67.5 centimeters. Echocardiography showed a left ventricle dilated to 38 millimeters, a z-score of +5.7 relative to normal body size, an ejection fraction of only 15 percent, and severe mitral regurgitation; his BNP had surged to 7667 pg/mL. Soon after arrival he developed runs of non-sustained ventricular tachycardia, a dangerous rhythm disturbance, and amiodarone therapy dropped his blood pressure. The team established venoarterial extracorporeal membrane oxygenation through neck vessels as an emergency salvage measure, but acute pulmonary congestion followed, forcing the decision to implant a biventricular assist device using centrifugal pumps. For the left side, surgeons used a 6-mm apical inflow cannula and a 6-mm arterial outflow cannula; for the right side, they placed a 14-Fr inflow cannula into the inferior vena cava via the right atrium and an 8-Fr outflow cannula into the distal pulmonary artery trunk, all secured with purse-string sutures.

What happened next is the technical heart of the report. The right ventricular assist device pumped roughly 900 mL/min, yet the left-sided pump could not function efficiently. The culprits were severe pulmonary hypertension and pulmonary regurgitation, which together prevented blood pushed into the pulmonary circulation from returning effectively to the left heart. In a decisive maneuver, the surgeons relocated the right-sided outflow cannula from the pulmonary artery into the left atrium, temporarily routing oxygenated blood directly to the left side of the heart and bypassing the obstructed pulmonary circuit. Left ventricular assist device flow stabilized at approximately 600 mL/min. The strategy bought time, but it carried trade-offs: left atrial cannulation raises the risk of systemic thromboembolism, and the circuit could not be disconnected from the artificial lung that oxygenates blood outside the body. The team therefore treated the configuration as a bridge within a bridge, to be dismantled as soon as the pulmonary vasculature could tolerate normal routing.

That evaluation came quickly. Cardiac catheterization on postoperative day 5, performed during temporary interruption of right-sided pumping, recorded a pulmonary artery pressure of 21/15 mmHg with a mean of 18 mmHg and a pulmonary vascular resistance index of 3.5 Wood units times meters squared, values indicating acceptable pulmonary vascular physiology. On postoperative day 13 the outflow cannula was moved back to the pulmonary artery trunk and the artificial lung was removed from the circuit. Bedside echocardiography then showed improving right ventricular contraction, but chest X-rays revealed progressing pulmonary congestion, which the surgeons attributed to excessive pulmonary blood flow generated by full right-sided support. Their response was a careful titration: right pump flow was gradually reduced to low-flow assistance. Throughout this period the left pump maintained a stable 900 mL/min flow and central venous pressure held near 12 mmHg even when right-sided support fell to 400 mL/min or was interrupted entirely, evidence that the native right ventricle and pulmonary circulation had recovered enough to fill the left pump on their own. Concerned about circuit thrombosis during prolonged low flow, the team removed the right ventricular assist device on postoperative day 20.

The recovery of other organs lagged behind the heart but eventually followed. Acute kidney and liver failure complicated the early postoperative course, requiring continuous hemodiafiltration from postoperative day 7. Bilirubin climbed as high as 15.1 mg/dL and renal dysfunction persisted for more than a month, but hemofiltration was discontinued on day 44, total bilirubin normalized on day 61, and the child was extubated on day 55. Only after these markers of end-organ recovery did the team secure in-house approval for heart transplant registration, the prerequisite under Japanese rules for implanting the Berlin Heart EXCOR, which was converted from the temporary centrifugal left ventricular assist device 76 days after the original biventricular implantation. The boy then remained stable on the pulsatile device for 374 days before undergoing successful heart transplantation, a total mechanical support journey of roughly 450 days from the first emergency pump to the donor heart.

The Osaka team frames the case within a strategy known as bridge to candidacy, an approach better documented in adults. In Japan, pediatric candidates face an average wait of 686 days for a donor heart, even though ten-year survival after pediatric transplantation reaches 96.2 percent, and by 2022 only 68 patients under 18 had ever been transplanted in the country. The Berlin Heart EXCOR has been approved there only since 2015 and only for patients already registered for transplantation, which creates a chicken-and-egg problem for infants whose comorbidities disqualify them from listing. Adult data show the workaround can succeed: large series report that short-term mechanical support can reverse refractory cardiogenic shock long enough for conversion to durable devices, with survival comparable to direct bridge-to-transplant pathways, though right ventricular support during the conversion emerges as a mortality risk factor. Pediatric evidence is thinner, but a Berlin group’s ten-year experience with 56 children and a multicenter United States study both suggest that prior extracorporeal support does not necessarily doom Berlin Heart outcomes, while low body weight, kidney and liver dysfunction, and biventricular support do worsen survival.

The case also contributes to a re-evaluation of Barth syndrome itself as a transplant indication. Because the condition combines heart failure with skeletal myopathy and immune compromise, patients were once considered unsuitable candidates, but after the first successful transplant in 1997, London investigators reported four successful cases, and a registry analysis of 43 transplanted Barth patients found outcomes for survival, infection, malignancy, and graft vasculopathy essentially equivalent to those of other recipients. The Osaka authors add an important caveat drawn from recent metabolic studies: transplantation does not fully normalize exercise tolerance, muscle mass, or substrate metabolism, because the underlying cardiolipin defect persists in skeletal muscle and other tissues. Their patient was not systematically assessed for these parameters after transplantation, a limitation the team acknowledges, and long-term multidisciplinary follow-up of neurodevelopment and metabolic status continues.

Beyond the individual rescue, the report is a detailed argument for staged, physiology-driven management of the failing right heart in small children. When pulmonary hypertension and valve regurgitation sabotage the left-sided pump, temporarily diverting right-sided outflow to the left atrium can stabilize the circulation; once catheterization confirms that pulmonary vascular resistance has fallen, rerouting to the pulmonary artery removes the thrombotic risk of left atrial cannulation and permits artificial lung removal, and stepwise flow reduction then tests whether the native right ventricle can carry the load. In this case that sequence converted a child in refractory cardiogenic shock with failing kidneys and liver into a registered transplant candidate with a durable device. The authors suggest the approach may extend the bridge-to-candidacy strategy to other high-risk pediatric patients with biventricular failure complicated by pulmonary hypertension, a population for whom waiting lists are long and options have historically been few.

Subject of Research: Bridge-to-candidacy mechanical circulatory support and heart transplantation in a pediatric patient with Barth syndrome-associated biventricular heart failure

Article Title: Successful bridge to heart transplantation in a pediatric patient with biventricular heart failure associated with Barth syndrome: a case report

Article References: Arita, K., Kido, T., Taira, M., Watanabe, T., Narita, J., Ishida, H., Ishii, R., Ueno, T., & Miyagawa, S. (2026). Successful bridge to heart transplantation in a pediatric patient with biventricular heart failure associated with Barth syndrome: a case report. Journal of Artificial Organs, 29(4), Article 60. https://doi.org/10.1007/s10047-026-01587-2

Image Credits: AI Generated

DOI: 10.1007/s10047-026-01587-2

Keywords: Barth syndrome, heart transplantation, ventricular assist device, Berlin Heart EXCOR, biventricular heart failure, pediatric cardiology, pulmonary hypertension, cardiogenic shock, mechanical circulatory support, TAZ gene, dilated cardiomyopathy, bridge to candidacy

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

The review, led by Marissa C. Kuo and W. Christian Crannell of Vanderbilt University Medical Center with colleagues across Vanderbilt’s surgical, nephrology, biomedical engineering, and cardiac surgery departments, synthesized preclinical and clinical evidence on 10 degrees Celsius static storage in heart, lung, liver, and kidney transplantation. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis scoping review guidelines, the team searched PubMed, Embase, Web of Science, and Scopus on May 22, 2025, returning 1,182 articles. After duplicate removal and independent screening by two reviewers, 45 studies met inclusion criteria, supplemented by 8 studies retrieved from reference lists and 15 additional references covering perfusion strategies, mitochondrial biomarkers, and controlled rewarming. The result is the most complete picture to date of a preservation approach that is quietly reshaping transplant practice.

The strongest evidence comes from lung transplantation. In animal models, storage at 10 degrees Celsius compared with conventional ice has been associated with improved oxygen uptake, lower airway pressures, greater lung compliance, less edema, better arterial oxygenation, and lower pulmonary vascular resistance after transplantation. Biochemical markers of inflammation, including interleukin-8 and interleukin-1 beta, were lower after reperfusion in organs kept at the warmer temperature. Metabolomic studies add mechanistic depth: in a porcine model, lungs stored at 10 degrees Celsius showed upregulation of protective metabolites such as glutathione and ascorbate, downregulation of substrates that induce mitochondrial depolarization, and elevated mitochondrial respiration supported primarily by complexes I and II. Lipid byproducts dominated the metabolite profile, suggesting that beta-oxidation may serve as an alternative energy substrate that keeps graft metabolism gently active, an organ-protective state the authors liken to hibernation.

Clinical experience in lungs has moved rapidly from proof of concept to multicenter trials. A 2021 pilot study of five bilateral lung transplants using 10 degrees Celsius storage reported zero cases of grade 3 primary graft dysfunction, no need for postoperative extracorporeal membrane oxygenation, and 100 percent 30-day survival. A retrospective matched cohort study found that preservation times extending up to 24 hours at 10 degrees Celsius produced no differences in mechanical ventilation time, intensive care or hospital stay, primary graft dysfunction rates, or survival compared with ice storage. A single-institution prospective study and the largest trial to date, a multicenter non-randomized prospective study of 70 donor lungs stored at 10 degrees Celsius overnight and transplanted the next morning, both found outcomes equivalent to conventional storage, with the multicenter trial reporting primary graft dysfunction rates of 5.7 percent versus 9.3 percent in controls. An international randomized non-inferiority trial has recently completed enrollment and may settle the question definitively.

The clinical implications extend beyond graft function into the logistics of transplantation itself. Because organs stored at 10 degrees Celsius tolerate longer cold ischemic times, surgical teams can schedule transplants during daytime hours rather than performing emergency operations in the middle of the night. Case reports describe hearts transported more than 10 hours without machine perfusion, from Anchorage, Alaska to Nashville, Tennessee, and sequential transplantation of two lungs from a single donor into two different recipients at different institutions. For a field in which more than 23,000 waitlisted patients died awaiting a kidney transplant in the United States between 2020 and 2024, and nearly 31,000 died waiting for any organ, every hour of safe preservation time translates into more organs reaching more patients.

Heart transplantation data, though earlier in its development, are similarly encouraging. A propensity-matched cohort study using a reusable 10 degrees Celsius cooler for organ transport found lower lactate changes and slightly higher cardiac index at 24 and 72 hours postoperatively compared with ice storage, though primary graft dysfunction rates did not differ and donor characteristics were not perfectly balanced. A more recent study of hearts procured after thoracoabdominal normothermic regional perfusion found that 10 degrees Celsius storage was associated with reduced risk of primary graft dysfunction, lower postoperative vasoactive inotropic scores, decreased use of renal replacement therapy, shorter intensive care stays, and reduced six-month mortality. Animal work dating back decades supports the temperature window: canine and rat studies found mitochondrial structural changes were less severe below 14 degrees Celsius, and that high-energy phosphate content was severely depleted only when storage temperatures exceeded 10 degrees Celsius.

The biochemical rationale centers on the mitochondria. At deep hypothermic temperatures near 4 degrees Celsius, the oxygen-binding equilibrium of myoglobin strongly favors the oxygenated form, but cytosolic oxygen diffusion slows dramatically and mitochondrial respiration becomes markedly attenuated. In this near-static state, the mitochondrial proton-motive force collapses, forcing ATP synthase to run in reverse and hydrolyze ATP, while electron flow reverses through succinate dehydrogenase, causing succinate to accumulate, a metabolic hallmark of ischemia. Upon reperfusion, rapid oxidation of that succinate generates a burst of superoxide radicals that can trigger mitochondrial permeability transition pore opening, cytochrome c release, and apoptotic signaling. Released mitochondrial DNA then circulates as a damage-associated molecular pattern, activating innate immune pathways that contribute to graft inflammation and rejection. Moderate cooling to around 10 degrees Celsius, by contrast, appears to preserve slow, reversible electron transport, maintain mitochondrial ultrastructure, and keep myoglobin-mitochondrial oxygen coupling intact.

Evidence in liver and kidney transplantation remains thinner and more mixed. In a comprehensive porcine model of donation after circulatory death, 10 hours of 10 degrees Celsius static storage followed by normothermic perfusion produced superior hemodynamic profiles, more bile with higher pH and bicarbonate, and metabolomic evidence of less citric acid cycle dysfunction and mitochondrial oxidative damage than ice storage, but no human liver studies have yet been published. Older kidney studies yielded conflicting results, with some suggesting slightly higher temperatures may better preserve adenine nucleotide levels, and species differences in mitochondrial temperature responses complicate extrapolation to humans. A 2024 rat cell study found the highest viability at 10 degrees Celsius, and a single human deceased donor kidney transplant after 10 degrees Celsius storage achieved immediate graft function, the first patient in a larger prospective trial now underway.

The review also situates 10 degrees Celsius storage within the broader landscape of preservation technology, including oxygenated hypothermic perfusion and controlled rewarming. Randomized trials of hypothermic oxygenated perfusion in liver transplantation have shown fewer non-anastomotic biliary strictures and less early allograft dysfunction, while a kidney trial of extended criteria donors showed no benefit, possibly because organs were stored on ice before perfusion began. Controlled oxygenated rewarming studies suggest that a gentler temperature gradient at reperfusion protects mitochondrial coupling, a benefit that 10 degrees Celsius storage could amplify by starting closer to physiological temperature. Notably, no study has directly compared static 10 degrees Celsius storage with machine perfusion, and the authors suggest that a simple, inexpensive cooler could in some cases obviate the need for costly perfusion devices.

The authors are careful about the limits of the evidence. Definitive conclusions, they write, await well-designed randomized clinical trials capable of providing the highest quality evidence, and the data are far stronger for heart and lung storage than for liver and kidney. Yet the convergence of mechanistic plausibility, decades of animal data, and increasingly positive clinical experience has given the field reason to reconsider a fundamental assumption: that colder is always better. If ongoing randomized trials confirm the early signals, the humble bag of ice that has defined organ preservation since the advent of transplantation may give way to a precisely controlled 10 degrees Celsius, a change that costs little, requires no complex machinery, and could extend the reach of every donated organ.

Subject of Research: Static organ storage at 10 degrees Celsius as an alternative to conventional ice preservation in deceased donor heart, lung, liver, and kidney transplantation

Article Title: 10° Celsius Static Storage in Deceased Donor Organ Transplantation: A Narrative Review

Article References: Kuo, M. C., Breeding, E., Kiyimba, F., Gohar, E. Y., Walden, R. L., Bacchetta, M., & Crannell, W. C. (2026). 10° Celsius Static Storage in Deceased Donor Organ Transplantation: A Narrative Review. Current Transplantation Reports, 13(1), Article 31. https://doi.org/10.1007/s40472-026-00528-5

Image Credits: AI Generated

DOI: 10.1007/s40472-026-00528-5

Keywords: organ transplantation, organ preservation, 10 degrees Celsius storage, static cold storage, mitochondria, ischemia-reperfusion injury, lung transplantation, heart transplantation, cold ischemia time, machine perfusion, deceased donor, primary graft dysfunction