A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis.

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.

Remote Dielectric Sensing Before and After Discharge in Patients With ADHF: The ReDS-SAFE HF Trial.

BACKGROUND: Incomplete treatment of congestion often leads to worsening heart failure (HF). The remote dielectric sensing (ReDS) system is an electromagnetic energy-based technology that accurately quantifies changes in lung fluid concentration noninvasively. OBJECTIVES: This study sought to assess whether an ReDS-guided strategy during acutely decompensated HF hospitalization is superior to routine care for improving outcomes at 1 month postdischarge. METHODS: ReDS-SAFE HF (Use of ReDS for a SAFE discharge in patients with acute Heart Failure) was an investigator-initiated, multicenter, single-blind, randomized, proof-of-concept trial in which 100 patients were randomized to a routine care strategy, with discharge criteria based on current clinical practice, or an ReDS-guided decongestion strategy, with discharge criteria requiring an ReDS value of ≤35%. ReDS measurements were performed daily and at a 7-day follow-up visit, with patients and treating physicians in the routine care arm blinded to the results. The primary outcome was a composite of unplanned visits for HF, HF rehospitalization, or death at 1 month after discharge. RESULTS: The mean age was 67 ± 14 years, and 74% were male. On admission, left ventricular ejection fraction was 37% ± 16%, and B-type natriuretic peptide was 940 pg/L (Q1-Q3: 529-1,665 pg/L). The primary endpoint occurred in 10 (20%) patients in the routine care group and 1 (2%) in the ReDS-guided strategy group (log-rank P = 0.005). The ReDS-guided strategy group experienced a lower event rate, with an HR of 0.094 (95% CI: 0.012-0.731; P = 0.003), and a number of patients needed to treat of 6 to avoid an event (95% CI: 3-17), mainly resulting from a decrease in HF readmissions. The median length of stay was 2 days longer in the ReDS-guided group vs the routine care group (8 vs 6; P = 0.203). CONCLUSIONS: A ReDS-guided strategy to treat congestion improved 1-month prognosis postdischarge in this proof-of-concept study, mainly because of a decrease of the number of HF readmissions. (Use of ReDS for a SAFE discharge in patients with acute Heart Failure [ReDS-SAFE HF]; NCT04305717).

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Review of the allocation criteria for heart transplant in Spain in 2023. SEC-Heart Failure Association/ONT/SECCE consensus document.

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.

Impact of Advanced Age on the Incidence of Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stable Coronary Artery Disease in a Real-World Setting in Spain.

Patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) without myocardial infarction (MI) or stroke are at high risk for major cardiovascular events (MACEs). We aimed to provide real-world data on age-related clinical characteristics, treatment management, and incidence of major cardiovascular outcomes in T2DM-CAD patients in Spain from 2014 to 2018. We used EHRead® technology, which is based on natural language processing and machine learning, to extract unstructured clinical information from electronic health records (EHRs) from 12 hospitals. Of the 4072 included patients, 30.9% were younger than 65 years (66.3% male), 34.2% were aged 65-75 years (66.4% male), and 34.8% were older than 75 years (54.3% male). These older patients were more likely to have hypertension (OR 2.85), angina (OR 1.64), heart valve disease (OR 2.13), or peripheral vascular disease (OR 2.38) than those aged <65 years (p < 0.001 for all comparisons). In general, they were also more likely to receive pharmacological and interventional treatments. Moreover, these patients had a significantly higher risk of MACEs (HR 1.29; p = 0.003) and ischemic stroke (HR 2.39; p < 0.001). In summary, patients with T2DM-CAD in routine clinical practice tend to be older, have more comorbidities, are more heavily treated, and have a higher risk of developing MACE than is commonly assumed from clinical trial data.

Frailty Is Common in Heart Transplant Candidates But Is Not Associated With Clinical Events and Is Reversible After Heart Transplantation.

Assessment of frailty before heart transplant (HT) is recommended but is not standard in most HT protocols. Our objective was to evaluate frailty at inclusion in HT list and during follow-up and to assess the influence of baseline frailty on prognosis. A prospective multicenter study in all adults included in the nonurgent HT waiting list. Frailty was defined as Fried's frailty phenotype score ≥3. Mean follow-up was 25.9 ± 1.2 months. Of 99 patients (mean age 54.8 [43.1 to 62.5] years, 70 men [70.7%]), 28 were frail (28.3%). A total of 85 patients received HT after 0.5 ± 0.01 years. Waiting time was shorter in frail patients (0.6 years [0.3 to 0.8] vs 0.2 years [0.1 to 0.4], p = 0.001) because of an increase in priority. Baseline frailty was not associated with overall mortality, (hazard ratio 0.99 [95% confidence interval 0.41 to 2.37, p = 0.98]). A total of 16 transplant recipients died (18.8%). Of the remaining 69 HT recipients, 65 underwent frailty evaluation during follow-up. Patients without baseline frailty (n = 49) did not develop it after HT. Of 16 patients with baseline frailty, only 2 were still frail at the end of follow-up. Frailty is common in HT candidates but is reversible in most cases after HT and is not associated with post-transplant mortality. Our results suggest that frailty should not be considered an exclusion criterion for HT.

AL Amyloidosis and Multiple Myeloma: A Complex Scenario in Which Cardiac Involvement Remains the Key Prognostic Factor.

Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain (AL) amyloidosis and multiple myeloma (MM) is scarce and controversial. Herein we aim to address this topic in a large series of patients of a referral center. All consecutive AL amyloidosis patients treated at our center from January 2005 to April 2023 were prospectively enrolled in a clinical and epidemiological registry. 141 patients diagnosed with AL amyloidosis were included, of which 7 (5%) had localized whereas 134 presented with systemic disease. The heart was the most frequently affected organ (90.3%). 25 patients (18.7%) fulfilled the IMWG diagnostic criteria of MM (AL/MM). Time-dependent association between AL and MM showed that the synchronous pattern is more frequent than the appearance of a second primary malignancy. The diagnostic delay was six months (m). Patients with AL/MM had a poorer median overall survival (OS) than AL-only patients (35.5 m, CI 95% 0-88.9, vs. 52.6 m, CI 95% 16.7-88.5), but this difference was not statistically significant. The prognosis in AL is dominated by the heart involvement, which is massive in this series. In our Cox regression model, only three prognostic variables remain as independent prognostic factors: age, N-terminal pro-brain natriuretic peptide (≥8500 ng/L), and undergoing an autologous stem cell transplant, whereas left ventricular ejection fraction shows a marginal effect. More and large studies focusing on the AL/MM association are needed to uncover the characteristics and prognostic impact of this association.

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry.

AIMS: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.

Danon Disease Presenting as Eosinophilic Myocarditis: Key Role of Endomyocardial Biopsy.

A 21-year-old woman with a history of atopy, peripheral eosinophilia, Wolf-Parkinson-White syndrome, and 5 episodes of myocarditis was diagnosed with eosinophilic myocarditis. Despite adequate immunosuppressive treatment and resolution of the myocarditis episode, the patient developed dilated cardiomyopathy and presented with worsening of her functional class. Finally, genetic testing unveiled an additional diagnosis: Danon disease. (Level of Difficulty: Advanced.).

ß3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

AIMS: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective ß3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). METHODS AND RESULTS: The ß3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. CONCLUSIONS: SPHERE-HF is the first clinical trial to assess the potential benefit of ß3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS.

Evolving Indications for Heart-Lung Transplant in Spain.

BACKGROUND: The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants. METHODS: We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease. RESULTS: There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis. CONCLUSIONS: HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

Role of TGF-ß1 +869T>C polymorphism in renal dysfunction one year after heart transplantation.

BACKGROUND: Chronic kidney disease is a major complication after heart transplantation with wide inter-individual variability. Calcineurin inhibitor nephrotoxicity, mediated by transforming growth factor-beta1 (TGF-ß1), is an important contributing factor. Our objective was to evaluate the association between TGF-ß1 polymorphisms and renal dysfunction 1-year after heart transplantation. METHODS: Single-center observational study that included patients who received a first heart transplant between 1990-2013. According to the 1-year eGFR decline, patients were classified as "Stable" (decrease in eGFR<10% or eGFR>60 ml/min/1.73m2) or "Progressors" (decrease in eGFR>10% and eGFR<60 ml/min/1.73m2). "Progressors" were then subdivided by the degree of eGFR decrease in "Mild progressors" (10-30%) or "Rapid progressors" (>30%). The association between TGF-ß1 +869T>C polymorphism and other risk factors with the eGFR outcome was analysed. RESULTS: A total of 355 patients (78% male; 50.7 ± 11.8 years) were included. According to the 1-year eGFR decline, 220 patients (62%) were classified as "Stable" and 135 (38%) as "Progressors". TGF-ß1+869CC genotype was more prevalent in "Stable" vs "Progressors" group (20% vs 8%, p = 0.009). In the multivariate analysis, female sex (p 0.02) and eGFR<60 ml/min/1.73 m2 at first month post-heart transplant (p = 0.004) remained as risk factors of eGFR decline, and TGF-ß1 + 869CC genotype (p = 0.001) and renal dysfunction pre-heart transplant (p = 0.04) as protective factors. TGF-ß1 + 869CC genotype was less frequently found in "Mild progressors" compared to "Rapid progressors" [p = 0.019; OR (95%CI) = 0.19 (.05-.76)]. CONCLUSIONS: The TGF-ß1 +869CC genotype is associated with a lower risk of calcineurin inhibitor nephrotoxicity after heart transplant. This genetic susceptibility could enable a more personalized patient treatment.

Gender Differences in Cardiogenic Shock Patients: Clinical Features, Risk Prediction, and Outcomes in a Hub Center.

Introduction: There is scarce knowledge about gender differences in clinical presentation, management, use of risk stratification tools and prognosis in cardiogenic shock (CS) patients. Purpose: The primary endpoint was to investigate the differences in characteristics, management, and in-hospital mortality according to gender in a cohort of CS patients admitted to a tertiary hub center. The secondary endpoint was to evaluate the prognostic performance of the Society of Cardiovascular Angiography and Interventions (SCAI) classification in predicting in-hospital mortality according to sex. Methods: This is a retrospective single-Center cohort study of CS patients treated by a multidisciplinary shock team between September 2014 and December 2020. Baseline characteristics and clinical outcomes according to gender were registered. Discrimination of SCAI classification was assessed using the area under the receiver operating characteristic curve (AUC). Results: Overall, 163 patients were included, 39 of them female (24%). Mean age of the overall cohort was 55 years (44-62), similar between groups. Compared with men, women were less likely to be smokers and the prevalence of COPD and diabetes mellitus was significantly lower in this group (p < 0.05). Postcardiotomy (44 vs. 31%) and fulminant myocarditis (13 vs. 2%) were more frequent etiologies in females than in males (p = 0.01), whereas acute myocardial infarction was less common among females (13 vs. 33%). Regarding management, the use of temporary mechanical circulatory support, mechanical ventilation, or renal replacement therapy was frequent and no different between the groups (88, 87, and 49%, respectively, in females vs. 42, 91, and 41% in males, p > 0.05). In-hospital survival in the overall cohort was 53%, without differences between groups (52% in females vs. 55% in males, p = 0.76). Most of the patients (60.7%) were in SCAIE at presentation without differences between sexes. The SCAI classification showed a moderate ability for predicting in-hospital mortality (overall, AUC: 0.653, 95% CI 0.582-0.725). The AUC was 0.636 for women (95% CI 0.491-0.780) and 0.658 for men (95% CI 0.575-0.740). Conclusions: Only one in four of patients treated at a dedicated CS team were female. This may reflect differences in prevalence of severe heart disease at young (<65) ages, although a patient-selection bias cannot be ruled out. In this very high-risk CS population of multiple etiologies, overall, in-hospital survival was slightly above 50% and showed no differences between sexes. Treatment approaches, procedures, and SCAI risk stratification performance did not show gender disparities among treated patients.

Endomyocardial biopsy-confirmed myocarditis and inflammatory cardiomyopathy: clinical profile and prognosis.

INTRODUCTION AND OBJECTIVES: Endomyocardial biopsy (EMB) is the only technique able to establish an etiological diagnosis of myocarditis or inflammatory cardiomyopathy (ICM). The aim of this study was to analyze the clinical profile, outcomes, and prognostic factors of patients with suspected myocarditis/ICM undergoing EMB. METHODS: We retrospectively analyzed the clinical characteristics, histological findings, and follow-up data of all patients with suspected myocarditis or ICM who underwent EMB between 1997 and 2019 in a Spanish tertiary hospital. The diagnostic yield was compared using the Dallas criteria vs immunohistochemical criteria (IHC). RESULTS: A total of 99 patients underwent EMB (67% male; mean age, 42±15 years; mean left ventricular ejection fraction [LVEF], 34%±14%). Myocarditis or ICM was confirmed in 28% with application of the Dallas criteria and in 54% with the IHC criteria (P <.01). Lymphocytic myocarditis was diagnosed in 47 patients, eosinophilic myocarditis in 6, sarcoidosis in 3, and giant cell myocarditis in 1 patient. After a median follow-up of 18 months, 23 patients (23%) required heart transplant (HTx), a left ventricular assist device (LVAD), and/or died. Among the patients with IHC-confirmed myocarditis, 21% required HTx/LVAD or died vs 7% of those without inflammation (P=.056). The factors associated with a worse prognosis were baseline LVEF ≤ 30%, left ventricular end-diastolic diameter ≥ 60mm, and NYHA III-IV, especially in the presence of inflammation. CONCLUSIONS: EMB allows an etiological diagnosis in more than half of patients with suspected myocarditis/ICM when IHC techniques are used. IHC-confirmed inflammation adds prognostic value and helps to identify patients with a higher probability of developing complications.

Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective Study.

Background: Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV. Methods: We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria. Results: We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2, and CAV3 in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1-2-3 (primary end-point) did not show significant differences (0.92%, IQR 0.46-2.0 vs. 0.46%, IQR 0.075-1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195-2.0) vs. 0.9% (IQR 0.12-1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = -0.095). Conclusion: In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis. Clinical Trial Notation: Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT04791852.