Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. METHODS: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). RESULTS: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. CONCLUSIONS: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Optimization of Hypercholesterolemia Treatment after Heart Transplant: The Role of PCSK9 Inhibitors.

BACKGROUND: Previous studies have reported the benefit of statins after heart transplant (HT). However, the use of high-dose statins might be limited in some HT patients due to intolerance and interactions with immunosuppression or might not be enough to achieve low-density lipoprotein (LDL) cholesterol goals. Hyperlipidemia has been associated with coronary allograft vasculopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors might be a safe and effective option in HT patients with suboptimal lipid control. METHODS: In a retrospective study, we identified HT patients in our center with LDL cholesterol >100 mg/dL, after diet modifications and up-titration of statins to maximum tolerated dose, treated with PCSK9i. The primary endpoint was LDL reduction one month after, and secondary endpoints were the development of donorspecific HLA antibodies (DSA) and the presence of coronary allograft vasculopathy or rejection. RESULTS: From January, 2018, to January, 2024, we identified five HT patients treated with PCSK9 inhibitors. In all cases, evolocumab was used. A significant reduction in LDL cholesterol was observed (151.6 ± 13.5 mg/dl to 72.4 ± 14.6 mg/dl; p = 0.04, mean reduction 75.7 ± 14.1 mg/dl), as well as in total cholesterol (231 ± 34.6 mg/dl to 152.2 ± 38.9 mg/dl; p < 0.01, mean reduction 78.8 ± 22.2 mg/dl). A significant increase in HDL cholesterol was not observed (45.4 ± 10.9 mg/dl to 46.2 ± 11.1 mg/dl; p = 0.60). One patient developed DSA five years after treatment onset. Rejection and coronary allograft vasculopathy were not observed. CONCLUSION: PCSK9 inhibitors are safe and effective in reducing LDL in HT patients. However, larger studies are needed to clarify if they can reduce the development of coronary allograft vasculopathy.

Structural heart transcatheter interventions in orthotopic cardiac transplant and left ventricular assist devices recipients: A nationwide study.

BACKGROUND: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown. AIMS: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain. METHODS: Multicenter, ambispective, observational nationwide registry. RESULTS: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device. CONCLUSIONS: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.

Spanish heart transplant registry. 34th official report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The Spanish heart transplant registry updates its data annually. The current update presents the data for the year 2022. METHODS: We describe the main clinical characteristics, treatments received, and survival outcomes including procedures performed in 2022, along with their trends since 2013. RESULTS: In 2022, 311 cardiac transplants were performed, representing a 3.0% increase compared with 2021. Compared with previous years, no significant changes in demographic and clinical characteristics were observed in 2022, confirming the trends identified in the last decade. These trends indicate a decrease in urgent procedures and the use of circulatory support, particularly ventricular assist devices. In the last decade, survival rates at 1 and 3 years were 81.4% and 73.4% respectively, with a slight, nonsignificant improvement. CONCLUSIONS: In the last decade, there has been a stabilization in the characteristics of heart transplant procedures and their outcomes. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study.

INTRODUCTION AND OBJECTIVES: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. METHODS: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. RESULTS: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). CONCLUSIONS: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension.

Continuous-flow left ventricular assist device: Current knowledge, complications, and future directions.

Long-term continuous-flow left ventricular assist devices have become a real alternative to heart transplantation in patients with advanced heart failure, achieving a promising 2-year event-free survival rate with new-generation devices. Currently, this technology has spread throughout the world, and any cardiologist or cardiac surgeon should be familiar with its fundamentals and its possible complications as well as the advances made in recent years. The aim of this review is to describe current knowledge, management of complications, and future directions of this novel heart-failure therapy.

Pulmonary Vascular Remodeling and Prognosis in Patients Evaluated for Heart Transplantation: Insights from the OCTOPUS-CHF Study.

OBJECTIVE: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants. METHODS: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up. RESULTS: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events (mortality or heart failure-induced hospitalization) had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT (with a median estimated pulmonary artery systolic pressure of 42.0 mmHg, interquartile range (IQR) of 30.3-50.0 vs. 47.0 mmHg, IQR 34.6-59.5 and p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR 1.3-3.7 vs. 2.0 Wood units, IQR 1.4-3.2 and p = 0.99, and a median pulmonary artery wall thickness of 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm and p = 0.87). CONCLUSION: Pulmonary vascular remodeling (evaluated with echocardiography, right heart catheterization, and pulmonary OCT) was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.

Serum biomarkers of acute rejection: Towards precision medicine in heart transplant.

Despite the important changes in the management of heart transplantation in the recent decades, the use of endomyocardial biopsy is still necessary for the follow-up of these patients. However, this technique has several limitations, the most important being the substantial interobserver variability. In the last years multiple attempts have been made to find non-invasive assays for cardiac allograft surveillance, such as imaging modalities and serum biomarkers. This state-of-the-art review focuses on describing the different serum biomarkers that have been proposed for non-invasive diagnosis of acute rejection and that are paving the way towards precision medicine in the field of heart transplantation.

Management of Intracranial Hemorrhage During Pulsatile Long-Term Biventricular Support: When Necessity Is the Mother of Invention.

Despite improvements in device design and hemocompatibility, intracranial hemorrhage and stroke remain the most feared and devastating complications in patients under mechanical circulatory support. We present the case of a 48 year old man with advanced heart failure (INTERMACS 3) and severe biventricular dysfunction who underwent biventricular pulsatile paracorporeal device implantation (Berlin Heart Excor) as a bridge to candidacy. Although on the heart transplantation waiting list, the patient experienced an intracranial hemorrhage, which was successfully managed by switching to a less thrombogenic biventricular assist device (Levitronix Centrimag) using the Excor cannulae, thus enabling temporary withdrawal of antithrombotic therapy. Heart transplant was performed successfully with no significant complications.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Rationale and design of the optical coherence tomography observation of pulmonary ultra-structural changes in heart failure (OCTOPUS-CHF) study.

BACKGROUND: The assessment of vascular remodeling using optical coherence tomography (OCT) has been previously described in some types of pulmonary hypertension. However, evidence about its feasibility and clinical utility for evaluation of pulmonary arterial vasculopathy in advanced heart failure (HF) is scarce. Optical Coherence Tomography Observation of Pulmonary Ultra-Structural Changes in Heart Failure (OCTOPUS-CHF) study is designed to study the correlation between OCT-morphometric parameters and hemodynamic data measured or derived from right heart catheterization (RHC). METHODS: OCTOPUS-CHF is an observational, prospective, multicentre study aiming to recruit 100 patients with advanced HF referred for heart transplantation (HTx) evaluation. As part of such evaluation, all patients will undergo RHC in order to rule out severe pulmonary hypertension. After RHC, a Dragonfly™ OPTIS™ imaging catheter will be used to perform OCT evaluation of a right-lower-lobe pulmonary artery with a luminal diameter ≤ 5 mm. The primary objective is to study the correlation of OCT parameters with hemodynamic RHC data. The secondary objective is to determine if OCT parameters improve prognostic stratification. CONCLUSIONS: The OCTOPUS-CHF study will investigate the feasibility and clinical utility of pulmonary arterial vasculopathy evaluation with OCT in advanced HF patients and its correlation with hemodynamic RHC data. The ability of OCT-morphometric parameters to improve prognostic stratification will also be tested.

Evaluation of a nurse-led intervention program in heart failure: A randomized trial.

BACKGROUND AND OBJECTIVE: Several trials have evaluated the effect of disease management programs in heart failure (HF) with diverse results. The aim of this study was to develop a simple nurse-led clinic intervention program for patients with HF and assess whether this intervention positively affects the prognosis of patients, their care costs and perceived quality of life (QoL). METHODS: Between 2011 and 2013, 127 patients with reduced ejection fraction were prospectively randomly allocated (1:2) to standard care or intervention program. Primary composite endpoint was all-cause mortality and hospital readmissions. Secondary endpoints were all-cause mortality, all-cause hospital readmissions, readmissions for HF, time to first readmission and QoL improvements assessed by "Minnesota Living with Heart Failure Questionnaire" (MLHFQ). An intention-to-treat analysis was performed. RESULTS: After a median follow-up of 2-years, no differences were found in the primary composite endpoint. Likewise, there were no differences between groups in the predefined secondary endpoints of mortality and readmissions from any cause. However, in the intervention group, readmissions for HF were significantly reduced (35% vs. 18%; p=0.04) and QoL significantly improved (MLHFQ±SD: 2.29±14 vs. 10.9±14.75; p=0.04). CONCLUSIONS: In patients with HF, the use of a nurse-led intervention program significantly improves perceived QoL and reduce HF hospital readmissions.

Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. / Enfermedad venooclusiva pulmonar y hemangiomatosis capilar pulmonar.

Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension which is part, together with pulmonary capillary hemangiomatosis, of the special designation (subgroup 1') within pulmonary hypertension group 1 in the latest classification of the pulmonary hypertension World Symposium. Recent discovery that gene mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) are responsible for inherited forms of pulmonary veno-occlusive disease has changed the role of genetic testing, acquiring relevant importance in the diagnosis of these patients. Despite the advances in genetic, cellular and molecular basis knowledge in the last decade, pulmonary veno-occlusive disease remains as a rare aetiology of pulmonary hypertension without any effective medical treatment approved and poor outcomes. This document aims to review the advances occurred in the understanding of pulmonary veno-occlusive disease in the last years.

Right-sided infective endocarditis in cardiac device carriers: Clinical profile and prognosis. / Endocarditis infecciosa derecha en portadores de dispositivos cardiacos: perfil clínico y pronóstico.

BACKGROUND AND OBJECTIVES: Due to the widespread indications for device implants and the population aging, right-sided infective endocarditis (RSIE) epidemiology has dramatically changed, being nowadays, cardiac device carriers the main affected group. The aim of this work is to describe the epidemiology, clinical profile and outcomes of RSIE in cardiac device carriers. PATIENTS AND METHODS: We included definitive infective endocarditis episodes consecutively diagnosed in 3 tertiary centers from March 1995 to September 2014. A retrospective analysis of 85 variables, one-year follow up and univariate analysis of in-hospital mortality was conducted. RESULTS: Among 1,182 episodes, 100 cardiac device carriers presented with RSIE (8.5%). Mean age±SD was 67±14 years. Staphylococcus spp. were the main causative microorganisms (coagulase-negative 44%, aureus 31%) and 37% were methicillin-resistant. Cardiac devices were removed in 95% of patients. In-hospital mortality was 8% and one-year mortality was 4%. Univariate analysis demonstrated that renal failure at admission (OR 6.2; 95% CI 1.3-30.3), septic shock (OR 8.9; 95% CI 1.7-47.9) and persistent infection during clinical course (OR 19.4; 95% CI 3-125.7) increase in-hospital mortality while device removal is a protective factor (OR 0.08; 95% CI 0.02-0.39). CONCLUSIONS: RSIE have low in-hospital and one-year mortality. Coagulase-negative Staphylococci is responsible of almost half of the episodes and methicillin-resistant incidence is high. Device removal is mandatory since it decreases in-hospital mortality.

Early mortality after heart transplantation related to IgA anti-ß2-glycoprotein I antibodies.

BACKGROUND: The presence of pre-formed IgA anti-ß2-glycoprotein I antibodies (IgA-aB2GP1ab) has been related to early graft loss after kidney transplant. Because ß2-glycoprotein I is produced in both the kidney and heart, we aimed to assess whether the presence of these antibodies may also be associated with poor outcomes after heart transplantation (HT). METHODS: A 2-year follow-up retrospective analysis of 151 consecutive patients who underwent HT between 2004 and 2012 was performed to assess the role of this pre-formed antibody type in HT. The population was divided into 2 groups according to the presence of IgA: Group 1 was positive for IgA-aB2GP1ab (47 patients, 31.1%), and Group 2 was negative for IgA-Ab2GP1ab (104 patients, 68.9%). RESULTS: Early mortality rates within the first 3 months were higher in Group 1 (27.7%) than in Group 2 (9.6%). No differences in donor and recipient characteristics or in causes of death were observed between groups. Multivariate analysis identified the presence of IgA-aB2GP1ab, female gender and blood type A as independent risks factors for early mortality after HT. A greater incidence of thrombotic events during the first 3 months post-HT in Group 1 (23.4% vs 5.8%) and a greater presence of risk factors for thrombotic events, which may have exacerbated them, were observed. After this period, no increase in mortality or in thrombotic events was found when the 2 groups were compared. CONCLUSION: Pre-transplant presence of IgA-aB2GP1ab is associated with both increased early mortality rates and higher thrombotic events after HT.