The Journal of Heart and Lung Transplantation

Preoperative anaemia is common in adults undergoing cardiac surgery and may identify patients at increased perioperative risk. This systematic review and meta-analysis synthesised contemporary observational evidence in accordance with PRISMA 2020. Five databases were searched for peer-reviewed English language studies published from 2017 to July 2026. Random effects meta-analyses used restricted maximum likelihood estimation with Hartung-Knapp confidence intervals; crude exact count estimates were synthesised primarily and adjusted estimates separately. Fourteen observational cohort studies involving 74,571 adults, including 17,349 (23.3%) with anaemia, were included. Preoperative anaemia was associated with red cell transfusion (OR, 3.66; 95% CI, 2.14-6.24), acute kidney injury or renal failure (OR, 2.43; 95% CI, 1.84-3.21), early mortality (OR, 2.11; 95% CI, 1.40-3.17), and postoperative infection (OR, 1.49; 95% CI, 1.21-1.82), but not postoperative stroke (OR, 1.16; 95% CI, 0.43-3.17). Certainty was low for renal outcomes and very low for the other outcomes. Preoperative anaemia is an important perioperative risk marker, particularly for transfusion and renal complications, although causality cannot be established.

Background: The Lung Transplant Frailty Scale (LT-FS) is a validated binary measure of frailty in lung transplant candidates. We aimed to refine the LT-FS Base and Body Composition measures by developing a three-category classification to improve clinical risk stratification with serum albumin as a more clinically practical frailty biomarker. Methods: To develop the refined LT-FS, we applied a 4-step measure development method to a multicenter prospective cohort study of lung transplant candidates. Low albumin (<3.5 g/dL) replaced high serum C-reactive protein ([&ge;]10 mg/L) as the LT-FS biomarker. Cutpoints that balanced discrimination, risk prediction, and calibration were identified to define ''frail'', ''pre-frail'', and ''not frail'' categories. Next, we evaluated associations between the refined LT-FS and exercise capacity, patient-reported outcomes, and mortality using multivariate linear and Cox regression. Results: Among 419 participants, the refined LT-FS identified a graded increase in mortality risk across frailty categories. For example, compared with candidates who were not frail, pre-frailty and frailty by the LT-FS Body Composition were associated with a 2.9-fold (HR 2.9, 95% CI 1.2-6.9) and 7-fold (HR 6.9, 95% CI 2.6-18.2) higher risk of waitlist delisting or death, respectively. Pre-frailty and frailty by LT-FS Body Composition were associated with 2-fold (HR 2.1, 95% CI 1.2-3.8) and 3.6-fold (HR 3.6, 95% CI 1.8-7.3) higher risk of mortality after transplant. Relationships with exercise capacity and patient-reported disability were less consistent. Conclusions: A refined Lung Transplant Frailty Scale incorporating serum albumin demonstrates strong associations with waitlist and post-transplant mortality. The addition of a pre-frail category better captures the continuum of frailty and improves clinical risk stratification of lung transplant candidates.

Background Studies of the 2018 United Network for Organ Sharing (UNOS) policy revision suggest improved early transplantation access for the sickest patients. It remains unknown whether these benefits vary as a function of time on the waitlist. Thus, we evaluated potential time-dependent effects of the 2018 heart allocation policy revision on waitlist outcomes. Methods Using UNOS data, we analyzed adult heart transplant candidates listed five years before (pre-policy) and after (post-policy) policy change, categorized as high-acuity (Status 1-3 or 1A) or low-acuity (Status 4-6 or 1B/old 2). Landmark analysis at weeks 0, 1, 2, 4, 8, 16, 24 using a competing risks framework was performed to assess transplantation, death/deterioration, and myocardial recovery. Sub-distribution and cause-specific hazard ratios were calculated. Absolute number and proportion of far-away transplants (donor distance [&ge;]500 nautical miles) were calculated at each timepoint. Results High-acuity patients experienced significantly higher risk of transplantation within 2 weeks post-policy change but equivocal risk by week 16. Low-acuity patients exhibited increased rate/risk of myocardial recovery and equal or improved death/deterioration risk at all timepoints; early transplantation cumulative incidence was increased. At all timepoints, both groups experienced significantly increased far-away donor use, highest immediately after listing and progressively declining over time. Conclusions The 2018 heart allocation policy change resulted in an initial appearance of time-dependent benefits among high-acuity, post-policy patients, but this was likely due to rapid transplantation of Status 1 and 2 patients from broader geographic sharing rather than a true temporal phenomenon. Post-policy, low-acuity patients experience benefits in all waitlist outcomes.

Background: Aortic stenosis (AS) is a valvular heart disease which imposes chronic pressure overload on the left ventricle (LV). Although LV remodelling may regress following aortic valve replacement, the molecular determinants of reverse remodelling remain poorly understood. This study develops a machine learning-based model using myocardial microRNA (miRNA) expression profiles to predict LV mass normalization one year after valve replacement. Methods: Consensus selection combining Random Forest and Bayesian Network analyses was applied to miRNA sequencing data from LV biopsies of 12 matched patient pairs with AS. Selected miRNAs were qPCR quantified in an extended cohort of 89 AS patients and incorporated into predictive models. Sex-stratified analyses were performed. Model robustness was assessed using bootstrap resampling and cross-validation. Candidate miRNAs and target genes were evaluated in LV from a murine model of pressure overload induced by transverse aortic constriction (TAC). Results: The combined Random Forest-Bayesian Network approach identified a three-miRNA signature (miR-517a-3p, miR-122b-5p, and miR-4683) associated with LV mass normalization after valve replacement. Validation in an extensive cohort demonstrated good overall discrimination and achieved its highest performance in women (AUC >0.80). Functional analyses identified drebrin (DBN1) as a putative target of miR-517a-3p and supported its potential involvement in pressure overload-induced cardiac remodelling. Conclusion: Random Forest and Bayesian Network integrated analyses enabled the identification of a myocardial miRNA signature with sex-dependent predictive value for reverse cardiac remodelling after aortic valve replacement. Functional validation supports the relevance of selected miRNAs and their downstream targets, highlighting their potential as biomarkers and candidate regulators of myocardial recovery.

BACKGROUND: Because of the high mortality rate associated with fulminant myocarditis (FM), there is limited evidence regarding the prognostic efficacy of endomyocardial biopsy (EMB). In this study, we aimed to evaluate the influence of EMB in the early phase after admission on treatment and prognosis in FM using a large-scale nationwide registry in Japan. METHODS: Patients with FM who required catecholamine or mechanical circulatory support between 2012 and 2017 from 235 hospitals across Japan were included. The primary outcome of death or heart transplantation within 90 days according to performance of early EMB were determined using Kaplan-Meier and Cox regression analyses. Factors associated with performance of early EMB, and subsequent medical treatment were analyzed. RESULTS: The median age of 736 patients with clinical FM was 56 years, and 407 patients (55%) received EMB. Most EMB (89%) were performed during the early phase (within 5 days of admission) and 63% were performed on the first day of admission. The prognosis of FM patients who underwent EMB was more favorable than that of those who did not based on the landmark analysis (log-rank test, P=0.04). Factor analysis demonstrated that FM patients who underwent EMB had a lower left ventricular ejection fraction, higher incidence of cardiogenic shock on admission, and higher rate of early mechanical circulatory support, as well as early initiation of corticosteroids and guideline-directed medical therapy (GDMT) for heart failure. Absence of any GDMT was associated with a less favorable prognosis on multivariate analysis (hazard ratio, 4.34 [95% CI, 3.14?6.01]; P<0.0001). CONCLUSIONS: Although performing EMB in the early phase after admission depends on disease severity in FM patients, it is associated with early initiation of advanced medical treatment and may contribute to improving the prognosis.

Objective: Dendritic cells (DCs) are priming local immune responses, and their tissue-associated activity increases in inflammatory conditions. In patients with coronary artery disease (CAD), circulating dendritic cell precursors (DCPs) are reduced. This study investigates circulating DCPs and tissue densities of migrated DCs in CAD patients undergoing bypass surgery, focussing on patients with chronic kidney disease (CKD) as a risk factor for CAD and a condition of chronic vascular inflammation. Approach and Results: Circulating DCPs were measured in the peripheral blood (before surgery) using fluorescence-activated cell sorting (FACS) in n=59 patients and results were compared with an age-matched healthy control group (n=45). DCs were stained (Fascin) in circular sections of the internal thoracic artery taken during bypass surgery and mature (CD83+) and immature (CD209+) DCs were differentiated. Cell densities were obtained digitally. Descriptive statistics and correlation analysis generated hypotheses. Circulating myeloid DCPs were reduced (p<0.001), concomitant CKD added no further reduction. Immature DCs were predominantly detected in the adventitia, mature DCs dominated in the intima (p<0.001). In CKD, reduced circulating myeloid DCPs correlated with immature DCs in the vessel wall (r=0.87; p=0.002) and rather mature DCs were detectable; in patients without CKD immature DCs were dominating. C-reactive protein correlated with mature DCs (r=0.38; p=0.026). Conclusions: Quantities of DCPs and mature and immature DCs vary between the vessel wall layers. The dominance of immature myeloid DCs in the adventitia suggests activation of the vascular-associated lymphoid tissue (VALT). Intensified inflammation associated with CKD may have promoted the maturation of myeloic DCs.

Aims: Myocardial strain enables sensitive assessment of cardiac function, but its clinical application has largely focused on individual chambers or selected patient populations. We evaluated the feasibility and clinical relevance of fully automated multi-chamber strain assessment in consecutive patients undergoing routine transthoracic echocardiography (TTE). Methods and results: This retrospective study included 8,350 consecutive adults undergoing TTE. A hospital-wide artificial intelligence (AI)-based system automatically measured left ventricular (LV) global longitudinal strain (LVGLS), left atrial (LA) reservoir strain (LASr), and right ventricular (RV) free-wall strain (RVFWS). AI-derived LVGLS was available from at least one apical view in 97.1% of patients and from all three views in 94.8%; LASr and RVFWS were available in 94.1% and 94.5%, respectively, resulting in complete multi-chamber strain assessment in 90.3%. Strain measures showed modest correlations with conventional chamber-specific echocardiographic parameters and differential associations with clinical outcomes. Gaussian mixture modeling identified three distinct clusters characterized by preserved multi-chamber function, RV-dominant dysfunction, and pan-chamber dysfunction. Compared with the preserved cluster, pan-chamber dysfunction was associated with the highest risk of all-cause death or heart failure hospitalization (adjusted hazard ratio, 3.44; 95% CI, 2.43-4.88; P<0.001). Prognostic associations remained evident in patients with LV ejection fraction (LVEF) [&ge;]50%, and cluster assignment provided incremental prognostic information beyond clinical factors, LVEF, and RV fractional area change. Conclusions: Fully automated multi-chamber strain assessment was feasible in a large consecutive TTE cohort. Integrating strain across cardiac chambers may provide complementary functional characterization and identify clinically relevant clusters with prognostic information beyond conventional assessment.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSLung donor-recipient matching requires balancing recipient medical urgency with expected post-transplant benefit. Conventional prediction models estimate outcomes for historical donor-recipient pairs but do not directly compare alternative candidates for the same donor. We developed an offline contextual-bandit framework to assess the feasibility of learning donor-centered lung-matching policies from historical registry data. MethodsWe used linked United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) Standard Transplant Analysis and Research files to identify 8,529 lung transplant allocation events from 2023 through 2025. Each event included the historical recipient and nine date-matched, ABO-compatible pseudo-candidates. The reward combined 72-hour respiratory-support-free survival (weight, 0.75) with a normalized initial Composite Allocation Score waitlist medical-urgency score (weight, 0.25). We trained a pessimistic neural lower-confidence-bound contextual-bandit policy (NeuraLCB) and evaluated it on held-out donor events using matched-action evaluation and self-normalized inverse propensity scoring (SNIPS). ResultsThe reconstructed dataset contained 85,290 donor-candidate rows. In the held-out set of 1,706 allocation events, the observed clinician reward was 0.534 (95% CI, 0.518-0.549). NeuraLCB agreed with the historical recipient in 174 events (10.2%), with a matched-action reward of 0.616. The SNIPS-estimated value of the NeuraLCB policy was 0.649 (95% CI, 0.568-0.717), corresponding to a paired difference of +0.116 (95% CI, +0.035 to +0.181) relative to observed clinician reward. However, the effective sample size was 51.5 events, indicating limited overlap between the learned and estimated historical policies. ConclusionsThis study demonstrates the feasibility of constructing and evaluating an offline contextual-bandit framework for lung donor-recipient matching using registry data. The estimated policy value was higher than the observed historical reward, but this finding is exploratory because candidate sets were reconstructed and off-policy evaluation had limited overlap. Verified offer sets, time-stamped candidate data, explicit compatibility constraints, and prospective evaluation are required before clinical use.

Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review

Background: Transthoracic echocardiography (TTE) remains the gold standard for assessing left ventricular (LV) diastolic dysfunction (DD), but noninvasive alternatives are needed to overcome geometric and acoustic limitations. 4D-Flow MRI enables comprehensive assessment of intraventricular pressure differences (IVPDs) and flow propagation velocity (VP). We aimed to evaluate 4D-Flow-derived IVPDs and VP in patients with hypertrophic cardiomyopathy (HCM). Methods: Thirty-eight HCM patients and 38 age- and sex-matched healthy controls underwent TTE and 4D-Flow MRI. Spatiotemporal maps of velocity and IVPDs, decomposed into inertial and convective components, were derived along the main inflow streamline from the mitral valve to the apex. Peak early filling rate (PEFR) was used to normalize IVPDs and VP. Results: While absolute peak flow rates were comparable, HCM patients exhibited significantly faster VP (100.4 vs. 60.2 cm/s, p < 0.01) and higher positive early E IVPD (1.40 vs. 0.92 mmHg, p < 0.01) compared to controls. Normalizing IVPDs by PEFR amplified group differences, revealing a markedly increased flow-normalized E-IVPD (5.13 vs. 2.94 x 103 mmHg.ml1.s, p < 0.001) and deeper reverse ER IVPD (-6.06 vs. -4.61 x 103 mmHg.ml1.s, p < 0.01) in HCM. These differences were primarily driven by the inertial components. Multivariable analysis demonstrated that ER IVPD is independently determined by PEFR and the TTE E/E' ratio (r = 0.65, p < 0.001). Conclusions: 4D-Flow MRI-derived, flow-normalized IVPDs and propagation velocity provide robust, noninvasive markers of altered LV chamber stiffness and impaired diastolic filling in HCM, offering deeper 3D hemodynamic insights into diastolic dysfunction.

Background. Fluid collections are common after kidney transplantation, but their prevalence at scheduled imaging and their management are inconsistent from canter to canter. We describe the cross sectional prevalence and management of perigraft collections, including an exploratory deepdrain subgroup. Methods. In this retrospective single center cohort, 146 consecutive adult kidney transplant recipients (Cleveland Clinic Weston Hospital, July 2024 to June 2025) were imaged on postoperative day 0/1 and at approximately 1 and 3 months. Routine deep drainage was avoided (n=124), 22 clinically selected recipients with perioperative anticoagulation received a deep drain. The primary outcome was cross sectional prevalence of a perigraft collection at each visit. Secondary outcomes were management among patients with a collection. Drain group comparisons were exploratory. Results. Collections were present in 29 of 146 recipients at postoperative day 0/1 (19.9%; 95% CI, 14.2 to 27.1), 71 of 146 at 1 month (48.6%; 95% CI, 40.7 to 56.7), and 34 of 146 at 3 months (23.3%; 95% CI, 17.2 to 30.8). Prevalence in the no drain group was 21.0%, 50.0%, and 23.4%, respectively; corresponding prevalence in the deep drain group was 13.6%, 40.9%, and 22.7%. Between group prevalence comparisons were not statistically significant at any time point. BMI was higher in the deep-drain group than in the no-drain group (30.04 vs 27.1 kg/m2; P=0.01). Among patients with a 1-month collection, management did not differ significantly between groups (any invasive management, 11.1% vs 16.1%; P=1.00). Among patients with a 3month collection, invasive management was more common in the deep drain group than in the no drain group (80.0% vs 13.8%; P=0.007). This comparison included only five deep-drain recipients and was confounded by clinical selection, perioperative anticoagulation, and BMI imbalance. Conclusions. Perigraft collection prevalence was highest at 1 month and lower at 3 months in this predominantly no drain cohort. Most collections were managed conservatively, and invasive treatment was uncommon in the no-drain group. The deep drain subgroup provides clinically relevant information about high risk recipients selected for drainage but cannot support causal conclusions regarding drain benefit or harm. Patient level linkage is required to distinguish persistence, resolution, and new collection formation.

BACKGROUND: While the systemic right and left ventricles have different functional prognoses, only a limited number of reports have addressed their myocardial architecture. This study analyzed myofiber orientation of human specimens with various congenital heart diseases using X-ray phase-contrast tomography. METHODS: Three specimens of each normal heart, ventricular septal defect, right atrial isomerism, left atrial isomerism, and ventricular inversion were examined. In reconstructed images of both ventricles, the center of the free wall was resliced parallel to the myocardial surface. A myofiber helical angle was identified in each slice and plotted from epicardium to endocardium. The plotted curves were compared between both ventricles. RESULTS: In all ventricles, the helical angle was changed from left-handed on epicardial slices to right-handed on endocardial slices. Whereas the right ventricle?s helical angle curves showed a plateau with or without a rapid rise on the endocardial side, the left ventricle?s curves had sustained increase with or without a plateau in the middle. The median wall-thickness?scaled helical angle change rates were 53{degrees} and 102{degrees} in the right and left ventricle, respectively, and their distribution of each specimen was higher in the left ventricle than in the right ventricle. CONCLUSIONS: Ventricular myofiber orientation has a consistent transmural helical transition independently of cardiac morphology and looping. Their transitions can have a plateau and rapid changes permitting the identification of layers within the ventricular wall. The left ventricle has more helical fibers and the right ventricle has more circumferential fibers, which may explain their difference of ventricular performance.

Rural patients with heart failure (HF) have poor access to care, worse outcomes, and may benefit from at-home monitoring. We evaluated whether foot temperature measured using a thermographic floor mat was associated with invasively measured cardiac output and whether longitudinal temperature changes preceded HF events. We conducted a two-part prospective, observational single-center study using the SmartMat (Podimetrics, Somerville, MA), which acquires plantar thermograms and ambient temperature. In the acute study, patients undergoing clinically indicated right heart catheterization completed 4 scans on the same day. In the chronic study, patients with a HF hospitalization in the past year and New York Heart Association Class II-III symptoms were instructed to use the device and a scale daily for 6 months. A HF event was defined as receiving at least one dose of intravenous or subcutaneous diuretic. Thirty patients were enrolled in the acute study. Mean right hallux temperature positively correlated with thermodilution cardiac output (r=0.63, p<0.001). 42 patients were enrolled in the chronic study. Among patients experiencing an HF event, ambient-adjusted hallux temperature declined in the 15 days immediately preceding the event compared with days 15-30 before the event. Plantar thermograms are associated with invasively measured cardiac output and may detect subclinical worsening before HF events. Foot temperature may provide complementary information regarding HF decompensation, supporting further evaluation of plantar thermography for remote HF monitoring.

Background: Patients with heart failure (HF) experience high mortality, yet survival estimates remain challenging. Available prognostic tools commonly predict survival beyond 1-year, limiting goals of care discussions and enrollment on palliative care programs. The objective of this project was to develop a novel prognostic score to better predict 6-month mortality. Methods: Patients with HF admitted to the St. Boniface Hospital (Winnipeg, Canada) between January 1, 2019 and January 1, 2024 were identified. Patient characteristics, imaging parameters, laboratory values, and functional assessments (Palliative Performance Scale; PPSv2) were collected. Patients were randomly divided into development (80%) and validation (20%) cohorts. Penalized LASSO regression was used to select variables most predictive of 6-month mortality in the development cohort. Retained variables were incorporated into a multivariable logistic regression model to derive the CARDIO-PAL score, the performance of which was assessed in the holdout validation cohort. Results: Characteristics were similar between the development (n = 2036) and validation (n = 508) cohorts, with 6-month mortality rates of 29% and 31%, respectively. 8 candidate variables were retained: age (adjusted odds ratio [aOR] 1.01), PPSv2 (aOR 2.08), systolic blood pressure (aOR 1.14), discontinued use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (aOR 2.58), beta-blocker (aOR 1.59), and mineralocorticoid receptor antagonist (aOR 2.67), right ventricular systolic pressure (aOR 2.06), and urea (aOR 2.13). The CARDIO-PAL score demonstrated good discrimination, with an area under the curve of 0.80 (95% confidence interval 0.75 - 0.84) and good calibration (slope 0.84, intercept -0.04). 6-month mortality across low, intermediate, and high-risk groups was 2%, 15%, and 54%, respectively. Conclusion: The CARDIO-PAL score is a novel tool to predict 6-month mortality in HF inpatients. A collaborative approach integrating CARDIO-PAL with other prognostic scores and serial clinical assessments has the potential to promote patient-centered care and improve referral to palliative care programs.

BackgroundMacitentan is a dual endothelin receptor antagonist used in pulmonary arterial hypertension (PAH) and has also been studied in other forms of pulmonary hypertension (PH). Evidence across PH phenotypes has been heterogeneous. This study aims to evaluate the efficacy and safety of macitentan compared with concurrent control therapies across PH phenotypes and to explore whether treatment effects differ according to PH classification. MethodsPubMed, Embase, and the Cochrane database were searched from inception through June 2026. Randomized and non-randomized comparative studies of patients with PH receiving macitentan were eligible. Prespecified efficacy outcomes were 6-minute walk distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), and cardiac index; prespecified safety outcomes included mortality and adverse events. Random-effects meta-analyses were performed using mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. ResultsFourteen studies met the eligibility criteria. Macitentan was associated with a greater reduction in PVR (MD, -134.50 dyn.s.cm; 95% CI, -226.10 to -42.86) and an increase in cardiac index (MD, 0.44 L/min/m; 95% CI, 0.22 to 0.67). No statistically significant difference was observed for 6MWD (MD, 5.04 m; 95% CI, -15.06 to 25.14) or mPAP (MD, -2.70 mmHg; 95% CI, -6.46 to 1.05). In pooled safety analyses, mortality was lower and risks of anemia, peripheral edema, and discontinuation due to adverse events were higher with macitentan. Heterogeneity and the small number of studies within several phenotype-specific analyses limited the precision of subgroup findings. ConclusionsMacitentan-containing therapy was associated with favorable changes in selected hemodynamic outcomes but not with a statistically significant improvement in 6MWD or mPAP. The safety findings were characterized by higher risks of anemia, peripheral edema, and treatment discontinuation. These results should be interpreted in the context of differences in PH phenotype, dose, comparator, study design, and outcome measurement.

Background: Sleep-disordered breathing (SDB) is an established adverse prognostic factor in heart failure (HF). Sleep apnea-specific hypoxic burden (SASHB), which reflects the duration and depth of respiratory event-related oxygen desaturation, has shown stronger prognostic value than the apnea-hypopnea index (AHI) in general populations and patients with coronary artery disease. However, its clinical utility in patients hospitalized due to acute HF remains unclear. Objectives: This study evaluated the prognostic value of SASHB in patients hospitalized for acute HF and compared its performance with AHI for risk stratification and identification of patients who may benefit from positive airway pressure (PAP) therapy. Methods: This post hoc analysis included 230 patients from a prospective single-center observational cohort of adults hospitalized for acute HF. The primary analysis included 178 patients who did not receive PAP treatment. Associations of SASHB and AHI with the composite endpoint of cardiovascular death or rehospitalization for worsening HF were evaluated using Cox proportional hazards models. Model improvement after adding SASHB or AHI to a model including established clinical risk factors was assessed using changes in the C index and Brier score, reflecting changes in model discrimination and prediction error, respectively. In the full cohort, the interaction between PAP treatment and SDB metrics was evaluated using the g-formula. Results: During a median follow-up of 3.7 years, 58 of 178 patients (32.6%) reached the composite endpoint. Both SASHB and AHI were independently associated with the composite outcome after multivariable adjustment. However, only SASHB consistently predicted outcomes across analyses and improved model performance beyond established prognostic factors (bootstrap {Delta} C index, 0.020 [95% CI: 0.008 - 0.031]; bootstrap {Delta} Brier score, - 0.007 [95% CI: - 0.014 to - 0.001]), whereas AHI did not. In the analysis including PAP-treated patients, both SASHB and AHI showed interaction with PAP treatment. Conclusions: In patients hospitalized for acute HF, SASHB showed a consistent independent association with adverse clinical outcomes and provided additional prognostic information beyond AHI. SASHB may improve risk stratification and may help identify patients who are more likely to benefit from PAP therapy.

Background: Mitral valve prolapse (MVP) causes mitral regurgitation (MR), leading to volume overload and maladaptive left ventricular (LV) remodelling. Objective: To comprehensively characterize markers of maladaptive LV remodelling across MR severity grades in MVP using cardiovascular magnetic resonance (CMR), and their association with functional status. Methods: Patients with MVP undergoing 1.5T CMR (2016-2025) were stratified by MR fraction: mild<20%, moderate 20-39%, and severe [&ge;]40%. Exclusion criteria were significant coronary artery disease, rheumatic valve disease, mitral stenosis, previous mitral valve procedures, endocarditis or signs of primary cardiomyopathy. Global native T1, T2, extracellular volume (ECV), indexed ECV (iECV), indexed intracellular volume (iICV), and late gadolinium enhancement (LGE) were quantified. Indexed LV end-diastolic volume (EDVI) and the EDV-to-LV mass ratio (EDV/LVM-ratio) were also calculated as indices of LV remodelling and adaptive hypertrophy. Functional status was assessed by NYHA class. Results: Among 112 MVP patients (23 mild, 48 moderate, 41 severe MR) and 20 controls, LGE prevalence (17% vs. 46% vs. 51% vs. 0%) and the proportion with LV dilatation (46% vs. 67% vs. 88% vs 15%) rose progressively with MR severity. Increased EDVI, prevalence of LGE, higher EDV/LVM-ratio, global native T1 and iECV showed the strongest associations with more severe MR, whereas EDV/LVM-ratio, iECV and global native T1 were independently related to NYHA class[&ge;]II. Conclusions: CMR markers of maladaptive LV remodelling were abnormal across all MR grades and increased markedly with MR severity. Global native T1, iECV and EDV/LVM-ratio correlated most strongly with symptom burden, rather than MR severity per se.

Introduction: In hypertrophic cardiomyopathy (HCM), wall stress and subclinical myocardial injury related in part to pathological hypercontractility, which in turn are associated with worse outcomes. Cell-free DNA (cfDNA) is released from cardiomyocytes (cfDNA-CM) through irreversible cellular injury and death. We investigated the feasibility of quantifying cfDNA-CM and its relationship to HCM patient characteristics. Methods: We analyzed 57 plasma samples from stable patients with HCM and 10 plasma samples from patients with acute myocardial infarction (AMI). Plasma cfDNA was isolated from both groups. Whole genome bisulfite sequencing (WGBS) libraries were generated and sequenced with short-read sequencing. Methylation patterns were used for tissue deconvolution analysis and cell-specific cfDNA quantification. Results: Yields of cfDNA (p = 0.003) and cfDNA-CM (p = 0.002) fractions were higher in AMI controls than HCM, supporting the validity of the assay. Within the HCM cohort, the median cfDNA yield was 12.22 ng [IQR: 7.77, 18.94]. The cfDNA-CM fraction in this cohort ranged from 0% to 6.4% of total cfDNA. Higher cfDNA-CM tertiles were associated with higher body mass index (BMI, p=0.001), a greater prevalence of BMI 30 kg/m2 (p<0.001), and a higher prevalence of obstructive sleep apnea (p=0.038). No significant differences were observed in other demographic, genetic, and laboratory characteristics. Higher cfDNA-CM tertile was numerically associated with higher New York Heart Association (NYHA) functional class and left ventricular outflow tract (LVOT) obstruction, while circulating biomarkers of wall stress (NT-proBNP) and myocardial injury (troponin) did not differ across tertiles (p=0.83 and p=0.29, respectively). Conclusion: Isolation and quantification of cfDNA as well as detection of cfDNA-CM in chronic stable patients with HCM are feasible. Higher cfDNA-CM fraction was associated with increasing BMI and cardiometabolic comorbidity burden. The absence of association with traditional circulating biomarkers suggests that cfDNA-CM may reflect a distinct domain of myocardial health, injury, and adverse remodeling.

Background: Racial disparities in incident heart failure (HF) are well documented, yet the extent to which systemic inflammatory burden-shaped by structural determinants of environmental exposure-accounts for these disparities remains unquantified in multi-ethnic prospective cohorts. Methods: Among 6785 participants in the Multi-Ethnic Study of Atherosclerosis (enrolled 2000-2002; 4 racial/ethnic groups) followed for approximately 16 years, we estimated associations of 4 prespecified baseline inflammatory and hemostatic biomarkers (interleukin-6 [IL-6], C-reactive protein [CRP], fibrinogen, and D-dimer; per 1-SD increment) with incident HF (485 events) using Cox proportional hazards models. A composite inflammatory burden index was derived by principal components analysis. Race x biomarker multiplicative interactions were tested with Holm correction. Sequential biomarker adjustment quantified the percentage of the Black-White log-hazard difference explained relative to a clinical-only model. Robustness to ambient air pollution (PM2.5, NO2) was assessed in a geocoded subcohort. Results: All 4 biomarkers were independently associated with incident HF (IL-6: hazard ratio [HR], 1.20 [95% CI, 1.08-1.34]; D-dimer: 1.18 [1.06-1.30]; CRP: 1.14 [1.02-1.27]; fibrinogen: 1.13 [1.02-1.24]). The composite index (first principal component, 53.7% of variance explained) yielded an HR of 1.25 (1.12-1.39) per 1-SD increase. No multiplicative race x biomarker interaction was detected (all Holm-corrected P=1.0), indicating that the per-SD inflammatory hazard was directionally consistent across groups. Sequential biomarker adjustment reduced the Black-White log-hazard difference by 57.5%, a pattern consistent with-but not sufficient to prove-attenuation by inflammatory pathways. Associations were robust to PM2.5/NO2 co-adjustment. Conclusions: Inflammatory and hemostatic burden partially explains the Black-White disparity in incident HF. The null multiplicative interaction pattern indicates that per-unit biological risk is equitable across groups, consistent with differential structural exposure-rather than differential susceptibility-as a primary driver of disparity. Key Words: heart failure; inflammation; health equity; structural determinants; MESA; biomarkers

Background Delayed graft function (DGF) is among the most used metrics in transplant medicine, yet its prevailing definition-dialysis requirement within the first seven postoperative days lacks granularity and fails to capture the dynamic nature of graft recovery. It reflects a treatment decision rather than graft biology, varies by centre practice, and offers no temporal information about the pace or pattern of recovery. This study proposes a trajectory-based framework using serial serum creatinine measurements across three biologically defined time windows to capture the dynamic nature of early renal recovery. Methods We retrospectively analysed 205 adult kidney transplant recipients at Cleveland Clinic Weston Hospital in 2025. Donor groups included living donors, donation after brain death (DBD), donation after circulatory death with normothermic regional perfusion (DCD-NRP), and DCD without NRP. Creatinine slopes were estimated for Days 1-7, 7-30, and 30-90 using ordinary least-squares regression. Logistic regression assessed the predictive performance of each trajectory window for DGF, adjusting for Kidney Donor Profile Index, cold ischemia time, BMI, and donor type. Results DCD non-NRP kidneys showed negligible early creatinine decline (slope +0.02) compared to DBD (-0.71) and DCD-NRP (-0.57) grafts during Days 1-7. During Days 7-30, DCD-NRP kidneys showed accelerated recovery and converged toward DBD-level trajectories, whereas DCD non-NRP grafts remained sluggish. Predictive modelling identified the Day 7-30 trajectory had the strongest discrimination for DGF, with AUC 0.83, pseudo-R2 0.25, and the lowest AIC (181.73), outperforming Days 1-7 (AUC 0.75) and 30-90 (AUC 0.79). DGF rates were 0% in living donors, 25.5% in DBD, 20.7% in DCD-NRP, and 58.9% in DCD non-NRP recipients. Conclusions A trajectory-based creatinine model provides more informative prognostic value than the conventional binary DGF definition The Day 7-30 window periods offers the highest discriminatory power, and normothermic regional perfusion appears to favourably shift DCD kidney recovery trajectories in a manner the binary definition fails to detect.