Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis.

OBJECTIVES: Lung transplantation (LuTx) is a life-saving intervention for Systemic Sclerosis (SSc) patients with end-stage lung disease. The aim of this study was to evaluate patients' survival and LuTx outcomes on systemic disease manifestations. METHODS: A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12, and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), global disease activity using a modified EUSTAR index (0-9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan-Meier analysis. RESULTS: 13 SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (p= 0.003). mRSS decreased from 7.4 ± 3.8-3.3 ± 2.5 in patients with dcSSc (p= 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (p= 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. CONCLUSIONS: In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

Prognostic Value of APACHE IV Score in Patients Bridged to Heart Transplantation on ECMO.

BACKGROUND: Methods for risk stratification of candidates for heart transplantation (HTx) supported by extracorporeal membrane oxygenation (ECMO) are limited. We evaluated the reliability of the APACHE IV score to identify the risk of mortality in this patient subset in a multicenter study. METHODS: Between January 2010 and December 2022, 167 consecutive ECMO patients were bridged to HTx; they were divided into two groups, according to a cutoff value of APACHE IV score, obtained by receiver operating characteristic curve analysis for 90-day mortality. Kaplan-Meier survival curves were plotted, and compared through the log-Rank test. Cox regression model was used to estimate which factors were associated with survival. RESULTS: The 90-day mortality prediction of the APACHE IV score showed an area under the curve of 0.87 (95% CI: 0.80-0.94), with a cutoff value of 49 (specificity 91.7%-sensibility 69.6%). 125 patients (74.8%) showed an APACHE IV score value < 49 (Group A), and 42 (25.2%) ≥ 49 (Group B). 90-day mortality was 11.2% in Group A and 76.2% in Group B (p < 0.01). Survival at 1 and 5 years was 85.5%, 77% versus 23.4%, 23.4% (p < 0.01) in Groups A and B. Mortality correlated at univariable analysis with recipient age, body mass index, mechanical ventilation, APACHE IV score, and platelets number. At multivariable analysis only APACHE IV score (HR: 1.07 [1.05-1.09, 95% CI]) independently affected survival. CONCLUSIONS: The APACHE IV score represents a powerful predictor of survival in patients bridged to HTx on ECMO support, and could guide candidacy of patients on ECMO.

Orthostatic Ex-Vivo Lung Perfusion (EVLP): A Proof of Concept.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Cytokines Removal During Ex-Vivo Lung Perfusion: Initial Clinical Experience.

Ex Vivo Lung Perfusion (EVLP) can be potentially used to manipulate organs and to achieve a proper reconditioning process. During EVLP pro-inflammatory cytokines have been shown to accumulate in perfusate over time and their production is correlated with poor outcomes of the graft. Aim of the present study is to investigate the feasibility and safety of cytokine adsorption during EVLP. From July 2011 to March 2020, 54 EVLP procedures have been carried out, 21 grafts treated with an adsorption system and 33 without. Comparing the grafts perfused during EVLP with or without cytokine adsorption, the use of a filter significantly decreased the levels of IL10 and GCSFat the end of the procedure. Among the 38 transplanted patients, the adsorption group experienced a significant decreased IL6, IL10, MCP1 and GCSF concentrations and deltas compared to the no-adsorption group, with a lower in-hospital mortality (p = 0.03) and 1-year death rate (p = 0.01). This interventional study is the first human experience suggesting the safety and efficacy of a porous polymer beads adsorption device in reducing the level of inflammatory mediators during EVLP. Clinical impact of cytokines reduction during EVLP must be evaluated in further studies.

Corrigendum: Five-Year Outcome After Continuous Flow LVAD With Full-Magnetic (HeartMate 3) Versus Hybrid Levitation System (HeartWare): A Propensity-Score Matched Study From an All-Comers Multicentre Registry.

[This corrects the article DOI: 10.3389/ti.2023.11675.].

Five-Year Outcome After Continuous Flow LVAD With Full-Magnetic (HeartMate 3) Versus Hybrid Levitation System (HeartWare): A Propensity-Score Matched Study From an All-Comers Multicentre Registry.

Despite the withdrawal of the HeartWare Ventricular Assist Device (HVAD), hundreds of patients are still supported with this continuous-flow pump, and the long-term management of these patients is still under debate. This study aims to analyse 5 years survival and freedom from major adverse events in patients supported by HVAD and HeartMate3 (HM3). From 2010 to 2022, the MIRAMACS Italian Registry enrolled all-comer patients receiving a LVAD support at seven Cardiac Surgery Centres. Out of 447 LVAD implantation, 214 (47.9%) received HM3 and 233 (52.1%) received HVAD. Cox-regression analysis adjusted for major confounders showed an increased risk for mortality (HR 1.5 [1.2-1.9]; p = 0.031), for both ischemic stroke (HR 2.08 [1.06-4.08]; p = 0.033) and haemorrhagic stroke (HR 2.6 [1.3-4.9]; p = 0.005), and for pump thrombosis (HR 25.7 [3.5-188.9]; p < 0.001) in HVAD patients. The propensity-score matching analysis (130 pairs of HVAD vs. HM3) confirmed a significantly lower 5 years survival (81.25% vs. 64.1%; p 0.02), freedom from haemorrhagic stroke (90.5% vs. 70.1%; p < 0.001) and from pump thrombosis (98.5% vs. 74.7%; p < 0.001) in HVAD cohort. Although similar perioperative outcome, patients implanted with HVAD developed a higher risk for mortality, haemorrhagic stroke and thrombosis during 5 years of follow-up compared to HM3 patients.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Pretransplant Right Ventricular Dysfunction Is Associated With Increased Mortality After Heart Transplantation: A Hard Inheritance to Overcome.

BACKGROUND: Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure because it precludes the implantation of left ventricular assist device, usually leaving heart transplantation (HTx) as the only available treatment option. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of preoperative RVD, hemodynamically defined as a low PAPi, with post-HTx survival. METHODS AND RESULTS: Consecutive adult HTx recipient at 2 Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were included retrospectively. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with the 1-year post-HTx mortality and other secondary end points were evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 Woods units vs <3 Woods units) were also performed. Among 657 HTx recipients (female 31.1%, age 53 ± 11 years), patients with pre-HTx RVD (PAPi of <1.68) had significantly lower 1-year survival rates (77.8% vs 87.1%, P = .005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio 2.0, 95% confidence interval, 1.3-3.1). RVD was also associated with post-HTx renal replacement therapy (hazard ratio 2.0, 95% confidence interval 1.05-3.30) and primary graft dysfunction (hazard ratio 1.7, , 95% confidence interval 1.02-3.30). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9% vs 88.3%, P = .003), but not in those with increased PVR (78.6% vs 83.2%, P = .49). CONCLUSIONS: Preoperative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters.

Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients.

Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in several solid organ transplants. We present a technically improved molecular method based on digital PCR that targets the mismatch between the recipient and donor at the HLA-DRB1 locus. Blood samples collected sequentially post-transplantation from a cohort of lung recipients were used to obtain proof-of-principle for the validity of the assay, correlating results with transbronchial biopsies and lung capacity tests. The results revealed an increase in dd-cfDNA during the first 2 weeks after transplantation related to ischemia-reperfusion injury (6.36 ± 5.36%, p < 0.0001). In the absence of complications, donor DNA levels stabilized, while increasing again during acute rejection episodes (7.81 ± 12.7%, p < 0.0001). Respiratory tract infections were also involved in the release of dd-cfDNA (9.14 ± 15.59%, p = 0.0004), with a positive correlation with C-reactive protein levels. Overall, the dd-cfDNA percentages were inversely correlated with the lung function values measured by spirometry. These results confirm the value of dd-cfDNA determination during post-transplant follow-up to monitor acute rejection in lung recipients, achieved using a rapid and inexpensive approach based on the HLA mismatch between donor and recipient.

Is there life on the airway tree? A pilot study of bronchial cell vitality and tissue morphology in the ex vivo lung perfusion (EVLP) era of lung transplantation.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a relevant procedure to increase the lung donor pool but could potentially increase the airway tree ischemic injury risk. METHODS: This study aimed to evaluate the direct effect of EVLP on the airway tree by evaluating bronchial cell vitality and tissue signs of injury on a series of 117 bronchial rings collected from 40 conventional and 19 EVLP-treated lung grafts. Bronchial rings and related scraped bronchial epithelial cells were collected before the EVLP procedure and surgical anastomosis. RESULTS: The preimplantation interval was significantly increased in the EVLP graft group (p < 0.01). Conventional grafts presented cell viability percentages of 47.07 ± 23.41 and 49.65 ± 21.25 in the first and second grafts which did not differ significantly from the EVLP group (first graft 50.54 ± 25.83 and second graft 50.22 ± 20.90 cell viability percentage). No significant differences in terms of histopathological features (edema, inflammatory infiltrate, and mucosa ulceration) were observed comparing conventional and EVLP samples. A comparison of bronchial cell viability and histopathology of EVLP samples retrieved at different time intervals revealed no significant differences. Accordingly, major bronchial complications after lung transplant were not observed in both groups. CONCLUSIONS: Based on these data, we observed that EVLP did not significantly impact bronchial cell vitality and airway tissue preservation nor interfere with bronchial anastomosis healing, further supporting it as a safe and useful procedure.

Antegrade Perfusion for Mini-Thoracotomy Mitral Valve Surgery in Patients with Atherosclerotic Burden.

BACKGROUND: The relationship between retrograde arterial perfusion and stroke in patients with peripheral vascular disease has been widely documented. Antegrade arterial perfusion has been favoured as an alternative approach in less invasive mitral valve (MV) operations. We aimed to analyse our experience in patients with peripheral arterial disease undergoing MV surgery through a right mini-thoracotomy adopting antegrade arterial perfusion. METHOD: A single-institution retrospective study on prospectively collected data was performed on patients undergoing right mini-thoracotomy MV surgery with antegrade arterial perfusion. Since 2009, indication for the latter was dictated by the severity of atherosclerotic burden. Preoperative screening included computed tomography, angiography, or both for the evaluation of the aorta and ileo-femoral arteries. RESULTS: Consecutive patients (n=117) underwent MV surgery through a right mini-thoracotomy with antegrade arterial perfusion, established either by transthoracic central aortic cannulation in 65 (55.6%) cases or by axillary arterial cannulation in 52 (44.4%). Mean logistic EuroSCORE was 11%±2.3%. Twenty-five (25) (21.4%) patients had undergone one or more previous cardiac operations. Operative mortality was 4.3% (n=5). Nonfatal iatrogenic aortic dissection occurred in one case (0.8%). The incidence of stroke was zero. CONCLUSIONS: Axillary or central aortic cannulation is a promising alternative route to provide excellent arterial perfusion in right mini-thoracotomy MV surgery, with a very low incidence of stroke and other major perioperative complications in patients with severe aortic or peripheral arterial disease.

Nonresponse to Acute Vasodilator Challenge and Prognosis in Heart Failure With Pulmonary Hypertension.

BACKGROUND: An acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge. METHODS AND RESULTS: This study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395). CONCLUSIONS: In patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis.

Fractional flow reserve guided versus angiographic guided surgical revascularization: A meta-analysis.

BACKGROUND: Clinical benefits of FFR (Fraction Flow Reserve) driven CABG (Coronary Artery Bypass Graft) remain to be established. METHODS: All randomized controlled trials (RCTs) and observational studies with multivariable adjustement were included. MACE (Major Adverse Cardiac Events) was the primary end point, while its single components (death, myocardial infarction, and total vessel revascularization [TVR]) along with number of anastomoses, on pump procedures and graft occlusion at angiographic follow-up were the secondary ones. Each analysis was stratified for RCTs versus observational studies. RESULTS: Four studies (two RCTs and two observational) were included, enrolling 983 patients, 542 angio-guided and 441 FFR-guided. Mean age was 68.45 years, 79% male, with a mean EuroSCORE I of 2.7. Coronary lesions were located in 37% of patients in the left anterior descending artery, 32% in the circumflex artery, and 26% in the right coronary artery. After a mean follow-up of 40 months, risk of MACE did not differ (OR 0.86 [0.63-1.18]) as that of all cause death (OR 0.86 [0.59-1.25]), MI (OR 0.57 [0.30-1.11]) and TVR (OR 1.10 [0.65-1.85]). FFR-driven CABG reduced on-pump procedures (OR 0.58 [0.35-0.93]) and number of anastomoses (-0.40 [-0.80: -0.01]) while incidence of graft occlusion at follow-up did not differ (OR 0.59 [0.30-1.15], all CI 95%). CONCLUSION: Fraction flow reserve driven CABG reduced the number of anastomoses and of on-pump procedures without increasing risk of MACE and without reducing graft occlusion at angiographic follow-up. ID CRD42020211945.

Right mini-thoracotomy approach for grown-up congenital heart disease.

BACKGROUND: Right mini-thoracotomy cardiac surgery has been recognized as a safe and effective procedure, with remarkable early and long-terms outcomes. However, most of the literature is focused on mitral valve surgery and few studies report on the minimally invasive approach applied to congenital disease. Aim of this study was to review our experience on patients with grown-up congenital heart (GUCH) undergoing right mini-thoracotomy cardiac surgery. METHODS: Data of patients with GUCH undergoing right mini-thoracotomy cardiac surgery from 2006 to 2019 were retrospectively analyzed. Inclusion criteria were atrial septal defect, partial anomalous pulmonary venous return, partial atrioventricular septal defect, and mitral or tricuspid valve dysfunction in congenital heart diseases. RESULTS: During the study period 127 patients with GUCH underwent right mini-thoracotomy cardiac surgery. Mean age was 43.6 years and more than 60% were females; diagnosis was atrial septal defect in 57 cases (44.9%); 24 patients were redo (18.9%). No cases of stroke and major vascular complications were reported. Conversion to sternotomy was required in one case (0.8%). No residual shunts or valves dysfunction were recorded at the postoperative echocardiographic evaluation. Perioperative mortality was 1.6%. CONCLUSIONS: Right mini-thoracotomy cardiac surgery in selected patients with GUCH allows to avoid the big scar of the sternotomy approach and to accelerate the recovery in a young population. Moreover, in redo cases, it allows the surgeon to reach the heart and the aorta avoiding the well-known risks of a re-sternotomy procedure.

Dabigatran etexilate in a vitamin-K antagonist non responder patient during Heartware HVAD support.

We report a case of a patient supported with a HeartWare left ventricular assist device for idiopathic cardiomyopathy who was resistance to vitamin-K antagonists three months after implantation. The patient initially started low-molecular-weight heparin therapy and then, after the onset of an ischemic stroke, switched to dabigatran etexilate (DE). The patient had progressive recovery of cardiac function for which the device was explanted. No thrombotic or bleeding events occurred during DE therapy.

Left Ventricular Unloading during Peripheral Extracorporeal Membrane Oxygenator Support: A Bridge To Life In Profound Cardiogenic Shock.

A limit of peripheral veno-arterial Extracorporeal Membrane Oxigenator (VA-ECMO) is the inadequate unloading of the left ventricle. The increase of end-diastolic pressure reduces the possibility of a recovery and may cause severe pulmonary edema. In this study, we evaluate our results after implantation of VA-ECMO and Transapical Left Ventricular Vent (TLVV) as a bridge to recovery, heart transplantation or long-term left ventricular assit devices (LVAD). From 2011 to 2014, 24 consecutive patients with profound cardiogenic shock were supported by peripheral VA-ECMO as bridge to decision. In all cases, TLVV was implanted after a mean period of 12.2 ± 3.4 hours through a left mini-thoracotomy and connected to the venous inflow line of the VA-ECMO. Thirty-day mortality was 37.5% (9/24). In all patients, hemodynamics improved after TLVV implantation with an increased cardiac output, mixed venous saturation and a significant reduced heart filling pressures (p < .05). Recovery of the cardiac function was observed in 11 patients (11/24; 45.8%). Three patients were transplanted (3/24; 12.5%) and three patients (3/24; 12.5%) underwent LVAD implantation as destination therapy, all these patients were discharged from the hospital in good clinical conditions. In these critical patients, systematic TLVV improved hemodynamic seemed to provide better in hospital survival and chance of recovery, compared to VA-ECMO results in the treatment of cardiogenic shock reported in the literature . TLVV is a viable alternative to standard VA-ECMO to identify the appropriate long-term strategy (heart transplantation or long-term VAD) reducing the risk of treatment failure. A larger and multicenter experience is mandatory to validate these hypothesis.

Does asymptomatic recurrent diffuse capillary C4d complement deposition impair cardiac allograft function?

BACKGROUND: The aim of this study was to evaluate whether asymptomatic recurrent (≥2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year after heart transplantation impairs left ventricular (LV) function. METHODS: Fifty-four consecutive heart transplant patients who survived well (New York Heart Association ≤2 and EF≥55%) the first month after transplantation were enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic rAMR without histopathologic findings was evaluated as a risk factor for deterioration of graft function. Primary endpoint, assessed 1 year after transplantation, was development of LV dysfunction and/or adverse remodeling according to pre-specified echo parameters. RESULTS: During the first year from transplantation, rAMR occurred in five patients. Recurrent AMR was associated with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95% CI: 1.8-7.0, P=.02) or reduced lateral S' peak velocity (OR 2.3, 95% CI: 1.5-3.6, P=.03). Patients with rAMR showed significative adverse graft remodeling (ΔLV end-diastolic volume: +16±12.3 vs -0.2±14.4 mL; P=.02) and deterioration of graft function (Δlateral S' peak velocity: -3.3±3 vs -0.4±2.9 cm/s; P=.03). CONCLUSIONS: Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction.