The Journal of Heart and Lung Transplantation

Residual congestion is the principal driver of heart failure readmission, and reliable serial assessment of volume status remains an unmet clinical need. This study asked whether a wrist-worn, machine-learning-based device for non-invasive venous waveform analysis in heart failure (the NIVAHF device), which produces an integer-scaled estimate of pulmonary capillary wedge pressure termed the NIVA Score, responds to acute changes in volume status. Agreement between the NIVA Score and invasively measured pulmonary capillary wedge pressure at single time points has been established in a separate prospective, multi-site study; however, such static agreement does not establish whether the measure tracks dynamic decongestion. We therefore evaluated the directional responsiveness of the locked NIVA Score in two prespecified cohorts: hospitalized adults with acute decompensated heart failure undergoing routine intravenous diuresis, and a controlled porcine model of volume overload followed by diuresis. In eleven patients contributing thirteen paired measurements (mean net fluid balance -2.1 {+/-} 1.0 L), NIVA Scores decreased significantly after diuresis (paired t-test, P = 0.04). In five pigs contributing twenty-four paired measurements, NIVA Scores decreased significantly after intravenous furosemide following crystalloid loading (P < 0.01), and the direction of change was concordant with measured urine output in every animal. Statistical significance was reached in both cohorts despite modest sample sizes, indicating a measurable NIVA Score reduction with volume removal. In an exploratory analysis, the discharge NIVA Score yielded an area under the receiver-operating-characteristic curve of 0.85 (95% confidence interval 0.575-1.00; P = 0.04) for thirty-day readmission. Together, the significant, directionally concordant NIVA Score reductions across independent clinical and preclinical cohorts demonstrate that the device tracks acute decongestion and support its use for serial, non-invasive congestion monitoring; an adequately powered prospective study is the planned next step.

Background: Gut injury after pediatric cardiac surgery remains an ongoing challenge, resulting in increased morbidity and mortality for children with congenital heart disease (CHD) and a significant burden on the healthcare system. It remains unclear what the driving forces are that result in this pro-inflammatory state following pediatric cardiac surgery with cardiopulmonary bypass. Understanding key components involved in the gut composition, gut barrier function, and systemic inflammation in children with CHD after cardiac surgery is critical to improve outcomes. Methods: A prospective study of patients aged 0-5 years with CHD undergoing cardiac surgery (CPB group) or non-CHD undergoing non-cardiac surgery (Comparison group). We collected pre-operative and post-operative stool and plasma to evaluate the microbiome, metabolites, markers of gut barrier function, and inflammatory cytokines. Clinical variables were collected to evaluate markers of inflammation. These variables were compared between the two groups to evaluate signatures and develop unique biomarker profiles. Results: We enrolled 62 patients (CPB, n=46; Comp, n=16). CPB patients had increased pro-inflammatory microbiota and reduced diversity metrics pre-operatively, which were exacerbated post-operatively. The CPB group also had increased pro-inflammatory eicosanoids and reduced gut and heart protective short-chain fatty acids versus the Comparison group. The CPB group had increased pro-inflammatory and reduced anti-inflammatory cytokines post-operatively. The CPB group also had increased markers of gut barrier dysfunction versus the Comparison group. Mediation analysis showed the microbial functional shift was associated with increased PGE2 and reduced butyric acid in the CPB group, associated with increased cytokines and clinical markers of inflammation post-operatively. Conclusion: We demonstrate unique gut microbial and metabolites profiles associated with gut permeability and systemic inflammation in children with CHD undergoing cardiac surgery highlighting a unique microbiome-inflammation axis in this patient population. Further studies to evaluate causal links with these profiles will identify potential targets to improve outcomes for these patients.

Background Donation after circulatory death (DCD) is an increasingly accepted strategy to expand the adult heart donor pool, but its use in children remains limited and incompletely characterized. We compared national characteristics and post-transplant outcomes of pediatric DCD versus donation after brain death (DBD) heart transplantation. Methods We performed a retrospective cohort study of the Organ Procurement and Transplantation Network (OPTN) registry, including patients younger than 18 years who underwent primary isolated heart transplantation between January 1993 and March 2025. Recipients were stratified by donor type (DCD vs DBD). Continuous variables were compared with the Mann Whitney U test and categorical variables with the Fisher exact test. Survival was estimated by the Kaplan Meier method and compared using the log-rank test and Cox proportional hazards regression. Results Of 10,671 pediatric heart transplant recipients, 33 (approximately 0.3%) received DCD allografts. The first DCD transplant was recorded in 2004, with a marked increase in 2023 to 2024. Compared with DBD recipients, DCD recipients were more frequently infants (<1 year, 51.5% vs 28.4%) and more often had congenital heart disease (69.7% vs 47.6%; P=0.033); DCD donors were younger (median 0 vs 6 years; P=0.038) and more frequently died of anoxia (72.7% vs 37.0%; P<0.001). Donor and recipient left ventricular mass were lower in the DCD group (P<0.05), but predicted left ventricular mass matching was similar. DCD recipients had longer hospital stays (median 31.5 vs 19 days; P=0.023); rates of treated rejection, dialysis, stroke, and pacemaker implantation were comparable. Early survival did not differ (30-day, 90-day, and 1-year), and Kaplan Meier survival through 5 years was not significantly different (hazard ratio 1.17; 95% CI 0.49 to 2.81; log-rank P=0.73). More than 90% of DCD transplants were performed in four UNOS regions (11, 4, 5, and 8). Conclusions In this national analysis, pediatric DCD heart transplantation was uncommon but expanding rapidly, concentrated in a few regions, and used preferentially in infants and children with congenital heart disease. Early post-transplant outcomes were not significantly different from DBD, supporting cautious expansion of DCD as a means of enlarging the pediatric donor pool. The small number of DCD recipients and limited followup warrant confirmation in larger, longer-term studies. Keywords: pediatric heart transplantation; donation after circulatory death; donor pool; congenital heart disease; OPTN registry; organ allocation.

Background: The saphenous vein (SV) remains the most widely used graft in coronary artery bypass grafting (CABG). However, graft failure over the years has compromised long-term outcomes. Preservation of the vascular endothelium is fundamental for vein graft patency, and hydrogen sulfide (H2S) a protective gasotransmitter, plays a significant role in vascular homeostasis. This study evaluated how different intraoperative preservation solutions modulate H2S-synthesizing enzymes and endothelial integrity. Methods: SV segments from 20 CABG patients were subdivided into five groups: Control (immediate fixation), normal saline (NS; 0.9% NaCl), autologous heparinized arterial blood (AHB), histidine-tryptophan-ketoglutarate (HTK) solution, and a damage group (no solution for 30 minutes). Structural integrity was evaluated by measuring endothelial coverage using light microscopy, and the expression of eNOS, CD31, and H2S pathway enzymes (CSE, CBS, and 3-MPST) was assessed by immunofluorescence (IF) and confocal microscopy to determine mean fluorescence intensity (MFI). Results: LM analysis revealed that AHB (89.66% {+/-} 3.02) and HTK (88.72% {+/-} 3.07) preserved endothelial coverage significantly better than NS (78.06% {+/-} 4.48) and the Damage Group (76.82% {+/-} 4.90; p < 0.001). In IF, all interventions reduced eNOS and CD31 expression compared to the control, but AHB and HTK maintained significantly higher levels than NS (p < 0.001). All three H2S-producing enzymes were detected in the GSV endothelium, with CSE being the most expressed isoform. The use of NS caused a marked depletion of these enzymes, while AHB and HTK showed specific superiority in preserving H2S synthesizing enzymes. Conclusions: The choice of preservation solution significantly affects endothelial integrity and the modulation of enzymatic H2S synthesis. NS proved to be deleterious to the endothelium, whereas AHB and HTK better preserved vascular structure and function, suggesting their clinical superiority for the preparation of venous grafts during CABG.

Background: Risk stratification in pericarditis relies mainly on clinical presentation, suspected etiology, imaging findings, and conventional inflammatory biomarkers. Whether complete blood count-derived inflammatory indices are associated with mortality in pericarditis and whether these associations are directionally consistent across independent real-world datasets remain unclear. Methods: We conducted a retrospective dual-cohort study of hospitalized adults with pericarditis using a Hong Kong cohort from the Clinical Data Analysis and Reporting System (CDARS) as the primary analysis cohort and the Medical Information Mart for Intensive Care IV (MIMIC-IV) cohort as an independent reproducibility cohort. Baseline neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) were analyzed as continuous variables and cohort-specific tertiles. The primary outcome was long-term all-cause mortality in the Hong Kong cohort. Secondary and reproducibility outcomes included 90-day mortality in the Hong Kong cohort and 30-day, 90-day, and observable follow-up mortality in MIMIC-IV. Cox models were adjusted for age, sex, renal disease, diabetes mellitus, hypertension, ischemic heart disease, and malignancy. Results: Among 504 patients in the Hong Kong cohort and 464 patients in MIMIC-IV, all-cause mortality occurred in 241 and 113 patients during cohort-specific follow-up, respectively. In the Hong Kong cohort, higher NLR was associated with long-term all-cause mortality after full adjustment. Compared with NLR tertile 1, the adjusted hazard ratio was 1.60 for tertile 3. Higher SII was also associated with long-term mortality, with an adjusted hazard ratio of 1.55 for tertile 3 versus tertile 1. NLR and SII showed directionally consistent associations with 90-day mortality in the Hong Kong cohort and with 30-day, 90-day, and observable follow-up mortality in MIMIC-IV. Sensitivity analyses yielded broadly consistent findings. Conclusions: In two independent real-world cohorts of hospitalized patients with pericarditis, higher baseline NLR and SII were associated with increased all-cause mortality, with NLR showing the more consistent prognostic signal. These complete blood count-derived indices may provide simple adjunctive information for mortality risk stratification, although prospective validation is needed before incorporation into formal management algorithms.

Background: Acute pulmonary embolism (PE) is a leading cause of morbidity and mortality with persistent difficulties in choosing interventions and predicting outcomes for patients defined clinically as intermediate risk. Computational fluid dynamics (CFD) tools have been used to understand the hemodynamic environment and plan interventions in the pulmonary arteries across a variety of disease conditions. Several biomechanical metrics have been used to evaluate risk in narrowed vessels, including hemodynamic resistance, power dissipation, and fractional flow reserve (FFR). In this study, we evaluate differences in these CFD-derived biomarkers between healthy controls (HC) and intermediate risk, acute PE patients. Additionally, we examine the response of patient hemodynamics to mechanical thrombectomy and compare values of these biomarkers across post-intervention pressure status. Methods: A CFD framework was developed to simulate patient-specific hemodynamics within the pulmonary vasculature identifiable from clinical imaging. The pipeline involved reconstructing three-dimensional (3D) structures of the pulmonary arteries and modeling blood flow with the finite element method. Patient-specific boundary conditions were derived from matching pre-intervention inlet mPAP to the patient's measured value given their measured CO as steady inflow. Converged simulations allowed for precise quantification of primary hemodynamic characteristics (flow and pressure) as well as secondary flow phenomena, primarily wall shear stress (WSS) and simulated pressure metrics such as fractional flow reserve (FFR). Results: Our simulations revealed significant elevations in resistance, power dissipation, and the number of vessels with low FFR in those patients with acute PE (n=6) compared to HC (n=3). Occlusions of hemodynamic significance were generally found in segmental pulmonary arteries. For patients with normalized pulmonary pressures post-thrombectomy (n=3), we found significantly higher proximal power dissipation and counts of low FFR vessels in comparison to those with elevated pressures after intervention (n=3). Distal resistance, which was derived from the portion of resistance attributed to the outflow boundary conditions, was significantly higher in patients with elevated pressures post-intervention. Across all PE patients, FFR count was significantly correlated with post-thrombectomy pulmonary pressure and cardiac index. Discussion: CFD-derived biomarkers offer a promising tool for understanding disease severity in acute PE. Differences between HCs and acute PE patients reveal expected increases in metrics associated with proximal disease burden. Yet, in examining acute PE patients with varying post-intervention hemodynamics, we found that these metrics of proximal disease burden could also be useful to predict the efficacy of mechanical thrombectomy. Those patients with normalized pressures had higher values for proximal disease metrics and lower values for distal disease metrics than those with continued elevations in pressure. This suggests that accessibility of hemodynamically-significant emboli to thrombectomy may be useful as a predictor for outcomes.

Background: Approximately 40 million individuals in the US have diabetes, and 6.5 million are also afflicted with congestive heart failure (CHF). This paper outlines the natural history of CHF in T2DM and compares CHF outcomes between patients with and without T2DM. Methods: We performed a retrospective analysis of prospectively collected data from 2,008 patients hospitalized for CHF exacerbation between December 2016 and June 2019. Propensity score matching was used to match diabetics and nondiabetics. Outcomes included survival and readmission rates at 28 d, 3 mo and 6 mo, as well as comparison of echocardiographic findings. Results: A total of 2,008 patients were included. After matching, 492 patients were included, with 244 diabetics and 248 nondiabetics. After matching, readmission rates within 28 days (p=0.625) were not different, but there was a trend for higher readmission rates among diabetics at 3 months (29.3% vs. 21.5%, p=0.049) and 6 months (44.3% vs 35.8%, p=0.053). Echocardiographic characteristics, including LVEF (p=0.135), LV EDV (p=0.707), maximum velocity of mitral valve E wave (p=0.407), maximum velocity of mitral valve A wave (p=0.050), E/A ratio (p=0.501) and tricuspid valve regurgitation pressure (p=0.668) were not different in the two groups. However, tricuspid valve regurgitation velocity was higher in diabetics (3.1 vs 2.9, p=0.003). Conclusions: Although diabetes poses an additional burden for patients with CHF, survival is similar in diabetics and nondiabetics. Nonetheless, readmission rates may be higher among diabetics. Tricuspid return velocity is higher in diabetics, suggesting early pulmonary vasculature remodeling.

Background: Outpatient chronic heart failure (HF) assessment relies on NYHA class and distance-based testing that can obscure physiological heterogeneity. Near-infrared spectroscopy (NIRS) enables tissue oxygenation phenotyping but is underexplored during standardized stressors in outpatient HF. We tested whether wearable NIRS-derived oxygenation kinetics during a vascular occlusion test (VOT) and six-minute walk test (6MWT) differ across NYHA classes. Methods: In this prospective, single-center pilot study, 44 chronic HF outpatients (mean age 70.9 {+/-} 8.7 years, 75% male; NYHA I [n=19], II [n=12], III [n=13]) were monitored with a novel wearable NIRS device (NIRSense Envello Core) during a VOT and 6MWT. Primary endpoints were the post-occlusion net area under the curve (net AUC; VOT) and post-walk recovery net AUC (modified 6MWT). Secondary endpoints included the exertional tissue oxygenation (Oxy) nadir, VOT reperfusion kinetics, gait metrics, and tolerability. Results: Despite NYHA I and II walking identical median distances (420 m), post-walk recovery net AUC was lower in NYHA II (-16.3 a.u.xs) and III (-12.8 a.u.xs) than NYHA I (46.1 a.u.xs, p=0.004). The exertional Oxy nadir did not differ (p=0.722), but NYHA III walked 27% and 38% slower than NYHA II and I (p<0.001). NYHA II had higher VOT net AUC (134.2 a.u.xs) than NYHA I (71.9; p=0.018) and III (61.1; p=0.011). Post-walk recovery net AUC correlated with gait velocity (rs=0.44) and distance (rs=0.39; both p<0.05). VOT net AUC did not correlate with functional metrics, but resting reperfusion kinetics correlated with 6MWT performance (rs=0.41-0.46, p<0.05). The sensor was well tolerated. Conclusions: Wearable NIRS-derived recovery kinetics differentiated NYHA I from NYHA II despite these classes walking identical median distances. Coupled with distinct resting VOT hyperemic differences, these preliminary findings indicate wearable NIRS may capture physiological heterogeneity in outpatient HF not reflected by NYHA class and standard functional metrics.

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of heart failure. With improved survival from disease-modifying therapies, an increasing number of patients are presenting for surgery and may be at increased risk of adverse postoperative outcomes. This study reports outcomes of ATTR-CM patients undergoing surgery and evaluates the utility of the Revised Cardiac Risk Index (RCRI), a perioperative risk tool. Methods: A total of 145 ATTR-CM patients were included, among which 51 patients underwent at least one eligible surgical procedure. Preoperative risk was assessed using the RCRI, analyzed both as a categorical and as a dichotomized ({greater than or equal to}3 vs <3) variable. Postoperative outcomes included unplanned hospital admission, length of stay (LOS), prolonged hospitalization (>48 hours), and major adverse cardiac events. Models were adjusted for frailty (Clinical Frailty Scale {greater than or equal to}5) and major surgery, using multivariable, ordinal, and Firth penalized logistic regression analyses. Results: Patients were predominantly male (86%) with a mean age of 76 {plus minus} 9 years, and 61% were frail. Higher RCRI scores were associated with unplanned postoperative hospital admission (RCRI {greater than or equal to}3: adjusted OR 48.9, 95% CI 4.8-502.2) and longer LOS (RCRI {greater than or equal to}3: adjusted OR 40.7, 95% CI 4.3-382.8). RCRI {greater than or equal to}3 was also associated with prolonged hospitalization (>48 hours) in Firth penalized logistic regression, whereas frailty was not independently associated. Conclusions: In a real-world ATTR-CM cohort undergoing major non-cardiac surgery, the overall risk of adverse outcomes was low, and higher RCRI scores were associated with increased postoperative hospital admission and longer LOS, including hospitalization exceeding 48 hours. The RCRI retains prognostic utility in this high-risk cohort and may support peri-operative risk stratification.

Background. Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of heart failure cases and is characterized by substantial clinical and biological heterogeneity. Sex differences are central to HFpEF pathophysiology, yet current phenotyping approaches often aggregate women and men, potentially obscuring distinct molecular mechanisms of disease progression. Molecularly resolved, sex-specific stratification is therefore needed to identify divergent risk pathways and improve biological understanding of HFpEF heterogeneity. Methods. In 698 HFpEF participants from the prospective MyoVasc cohort (379 females, 319 males), we run separate analyses on sex-specific cohorts. For each cohort, we integrated 92 circulating proteins (Olink Inflammation panel) and 49 clinical variables using Similarity Network Fusion to construct sex-stratified patient-patient similarity networks. Spectral clustering identified sex-specific prognostic subgroups related to the primary endpoint, i.e. worsening of Heart Failure (WHF). XGBoost models characterizing cluster-defining features were validated in an independent cohort of 342 HFpEF patients from the Gutenberg Health Study (GHS; 194 females, 148 males). Results. Two clusters emerged in each sex, with high-risk and low-risk clusters, showing the difference in WHF risk (MyoVasc females: HR 2.45, 95% CI 1.32-4.54, p=0.005; males: HR 2.77, 95% CI 1.27-6.04, p=0.011; C-index 0.62-0.63). Kaplan-Meier analyses confirmed separation (p<0.02 females, p<0.01 males). Clusters were reproduced in GHS using MyoVasc-trained XGBoost (females p=0.0082, males p=0.037). Shared top-ranking features included VEGF-A, TNFRSF9, and TGF-. Females were characterized by inflammatory (CD40, HGF, TNF) and glycemic signatures, whereas males showed prominence of immune-regulatory markers (IL-10RB, PD-L1) and renal function indicators (eGFR, creatinine). Conclusions. Sex-stratified molecular-clinical networks define prognostically distinct HFpEF subgroups with robust external validation. Shared protein biomarkers alongside sex-specific drivers reveal complementary progression mechanisms, supporting precision medicine strategies targeting high-risk cluster patients in sex-specific manner.

Background: Bicuspid aortic valve anatomy increases procedural complexity during transcatheter aortic valve implantation, yet outcome-oriented anatomic risk stratification for intraprocedural events remains limited. Aims: We aimed to develop and externally validate an anatomy-driven score to predict a composite intraprocedural endpoint, assessed at exit from the procedure room, in bicuspid transcatheter aortic valve implantation. Methods: Consecutive patients with bicuspid aortic valve undergoing transcatheter aortic valve implantation were analysed in a development cohort (N=793) and a multicentre external validation cohort (N=134). Candidate preprocedural computed tomography and echocardiographic variables were prespecified by expert consensus and refined using penalized regression with bootstrap stability selection within a domain-constrained framework. A five-indicator score (0 to 10 points) was derived from routine imaging metrics spanning the ascending aorta, aortic root, valve complex, annulus-outflow tract unit, and left ventricle, and tested using multivariable logistic regression. Results: The composite intraprocedural endpoint occurred in 101/793 (12.7%) patients in the development cohort, with stepwise increases across risk strata (7.2%, 13.3%, 30.6%; p<0.001). Each 1-point increase was independently associated with higher risk (odds ratio 1.32; 95% confidence interval 1.18-1.47). A similar gradient was observed in external validation (3.1%, 10.8%, 50.0%; p=0.012; odds ratio 1.55 per point), with a C-statistic of 0.725. Higher risk categories were associated with lower early safety and higher 30-day and 1-year mortality. Conclusions: An anatomy-driven score derived from routine preprocedural imaging demonstrates graded discrimination of intraprocedural risk and may inform procedural planning in bicuspid transcatheter aortic valve implantation.

Background: The fibrosis-4 index (FIB-4) is a simple noninvasive marker originally developed to assess liver fibrosis risk. Accumulating evidence suggests that FIB-4 is associated with adverse cardiovascular outcomes, but its prognostic relevance in patients with primary aldosteronism (PA) remains unclear. Methods: In this retrospective multicenter cohort study, patients with PA were stratified into low, intermediate, and high FIB-4 groups using established cutoffs: <1.3, 1.3-2.67, and >2.67. Outcomes included all-cause mortality, ischemic stroke, hemorrhagic stroke, acute myocardial infarction, and major adverse cardiovascular events (MACE). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) across FIB-4 categories. Results: Among 2,467 patients with PA, 1,215 (49.3%) had FIB-4 <1.3, 863 (35.0%) had FIB-4 1.3-2.67, and 389 (15.8%) had FIB-4 >2.67. Patients with higher FIB-4 were older and had lower body mass index, worse renal function, lower potassium, and a higher comorbidity burden. During follow-up, all-cause mortality increased across FIB-4 categories, from 13.9% in the low FIB-4 group to 58.1% in the high FIB-4 group. After multivariable adjustment, FIB-4 >2.67 was associated with higher risks of all-cause mortality (adjusted HR, 1.98; 95% CI, 1.54-2.54) and MACE (adjusted HR, 1.78; 95% CI, 1.44?2.20), compared with FIB-4 <1.3. Adjusted linear regression analyses showed that higher FIB-4 was significantly associated with lower renin and higher aldosterone-to-renin ratio. Conclusions: In patients with PA, elevated FIB-4 identified a high-risk subgroup with increased all-cause mortality and MACE. FIB-4 may serve as a simple, noninvasive tool for prognostic stratification in patients with PA.

Background: Neighborhood-level social determinants of health influence cardiovascular outcomes; however, their association with post-discharge healthcare utilization in heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. Methods: We conducted a retrospective cohort study of 6,702 adults hospitalized for HFpEF (2014 to 2022). Patients were assigned to one of four neighborhood environments (NEnv-1 to NEnv-4) using a validated clustering framework based on ZIP code-level socioeconomic variables. The primary outcome was time to first HF readmission, evaluated within prespecified post-discharge intervals (0-30 days, >30-90 days, and >90-365 days). Secondary outcomes included HF-related healthcare re-encounters and HF hospitalization burden (0, 1, or [&ge;]2 admissions). Cox proportional hazards and multinomial logistic regression models were used. Results: Neighborhood environment was independently associated with post-discharge outcomes with distinct temporal patterns. Early (0-30 days) HF readmission risk was higher in NEnv-3 (aHR, 1.63) and NEnv-4 (aHR, 1.76), with similar increases in HF-related re-encounters (aHR, 1.72 and 1.84) persisting through the >30-90-day interval. In contrast, NEnv-2 demonstrated a delayed-risk pattern, with the highest risk occurring in the >90-365-day interval (readmission aHR, 3.42; re-encounter aHR, 3.45). All non-reference environments were associated with a higher likelihood of at least one post-index HF admission (aOR range, 1.84-2.24). NEnv-4 uniquely demonstrated higher odds of recurrent hospitalization ([&ge;]2 vs. 1 admission; aOR, 1.64). Conclusions: Neighborhood environment is associated with distinct, time-dependent patterns of HF utilization in HFpEF, including early, delayed, and recurrent risks. Incorporating neighborhood context may help identify when patients with HFpEF are most vulnerable after discharge and guide the timing of post-discharge interventions.

Unplanned readmissions after liver transplantation occur in over 30% of recipients, yet no validated prediction models exist, and prior observational studies suffer from immortal time bias. The optimal readmission window for outcome prediction and the feasibility of early risk stratification remain undefined. This study is a retrospective analysis of 922 adult liver transplant recipients (August 2018-August 2025) at a single center. Time-varying Cox regression evaluated 14-, 30-, and 90-day readmission windows as predictors of 1-year mortality, correcting for immortal time bias. Gradient-boosted machine learning models leveraging 528,400 laboratory measurements (28 analytes) predicted 90-day readmission using either complete hospitalization data or data restricted to postoperative day 7. Feature importance was quantified by gain, and clinical utility was assessed through risk stratification. Among 902 hospital survivors, 342 (37.9%) experienced an unplanned readmission within 90 days of initial discharge. Only the 90-day readmission window predicted 1-year mortality in time-varying analysis (HR 1.73, 95% CI 1.17-2.57, p=0.006). The model for readmission using complete data achieved AUC 0.614 (95% CI 0.576-0.652); the postoperative day 7 restricted model achieved AUC 0.615 (95% CI 0.577-0.652), with no meaningful performance difference. The tacrolimus coefficient of variation x peak creatinine interaction was the dominant predictor in both the complete model (17.3% importance, rank 1) and the day 7 restricted model (20.4% importance, rank 2). This interaction stratified patients into high-risk (tacrolimus CV >0.3 and creatinine >2.0 mg/dL; 49.8% readmission) versus low-risk (24.8% readmission) groups (risk ratio 2.01, p<0.001). These results identify a modifiable biological determinant of readmission and establish a framework for targeted interventions to reduce unplanned readmission and improve post-transplant outcomes.

Tricuspid valve regurgitation is a frequent valve lesion and, if severe, an independent predictor of mortality. In most patients, the valve itself has historically been considered intact. Yet, we have previously shown that the valve may not be an innocent bystander. In multiple sheep models, we have shown that the tricuspid valve thickens and stiffens. This remodeling may contribute to valve disease. Our goal is to extend our investigation of tricuspid valve remodeling to a rodent model, potentially opening scientific opportunity and enabling scaling our studies. To this end, we used pulmonary artery banding (PAB) in male rats to induce pressure overload and right ventricular remodeling. After excising the tricuspid valve, we quantified anterior leaflet morphology, mapped anterior leaflet thickness using optical coherence tomography, and evaluated anterior leaflet belly mechanics using a custom bulge testing system. Compared with SHAM controls, PAB increased anterior leaflet area. Moreover, anterior leaflets in PAB animals exhibited region-specific thickening, with the largest increases near the annulus. Finally, anterior leaflets in PAB animals were significantly less compliant. However, leaflet stiffening stemmed from aforementioned thickening, i.e., structural stiffening, not constitutive stiffening. Our findings demonstrate that we can reliably quantify leaflet area, thickness, and stiffness in the minuscule tricuspid valves of rats. We also show that tricuspid valve remodeling is not ovine-specific, but also affects the tricuspid valves of rats. Together, our findings support our hypothesis that tricuspid valves are not innocent bystanders in regurgitation, and that rats may serve as a scalable model system for future investigations. NEW & NOTEWORTHYUsing a rat pulmonary artery banding model of pulmonary hypertension, we show that chronic right ventricular pressure overload induces leaflet enlargement and region-specific thickness remodeling of the tricuspid valve. Although structural mechanical metrics change under pressure loading, normalization by thickness reveals that geometric remodeling rather than intrinsic material stiffening predominates. These findings highlight leaflet structural (mal)adaptation as a potential contributor to functional tricuspid regurgitation and underscore the importance of considering leaflet geometry in therapeutic strategies.

Background: The PREVENT (Predicting Risk of CVD EVENTs) equations estimate the risk of incident cardiovascular disease (CVD) in primary prevention patients. We hypothesized that risk factors incorporated in the equations may be relevant to prognosis in heart failure (HF) and investigated the association between estimated CVD risk and clinical outcomes in patients with preserved ejection fraction (HFpEF). Methods: We estimated the 10-year CVD risk using the PREVENT equations in 278 patients hospitalized for acutely decompensated HFpEF (median 75 years, 51.4% male). We divided them into four groups according to the quartiles of estimated CVD risk and followed them to observe major adverse cardiovascular events (MACE), a composite of all-cause death, HF hospitalization, and stroke. Results: MACE occurred in 125 patients (45.0%) over a median follow-up of 1,050 days. The estimated CVD risk classification was an independent predictor for MACE (p=0.02) in the multivariable Cox proportional hazard model. There was a difference in MACE-free survival across the four quartile groups (p<0.001 by log-rank test), and the lowest CVD risk group had significantly lower MACE incidence than other groups. The estimated CVD risk provided incremental prognostic value beyond N-terminal pro-B type natriuretic peptide (C-index: 0.626 vs, P=0.009). The predictive value of the estimated CVD risk for MACE at 1 year was comparable to that of the MAGGIC score (AUC 0.676 vs. 0.639, p=0.42). Conclusions: The 10-year CVD risk estimated by the PREVENT equations had a moderate predictive value for MACE in patients hospitalized for HFpEF.

Background: Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden. Most electrocardiogram (ECG)-based artificial intelligence models are limited to diagnostic tasks or fixed-horizon prognostic classification and provide little insight into the temporal evolution of risk. In addition, concerns regarding model interpretability continue to impede clinical adoption. Whether deep learning applied to ECGs can deliver individualized, time-resolved, and biologically interpretable risk estimates for incident HFrEF across diverse populations remains uncertain. Methods: We developed a convolutional neural network-based survival model using raw 12-lead ECGs from Zhongshan Hospital (SHZS) and externally validated it in independent cohorts from Shanghai Tenth People's Hospital (SHTP) and Beth Israel Deaconess Medical Center (BIDMC). The model generated individualized, day-by-day probabilities of incident HFrEF over a 5-year horizon. Performance was comprehensively evaluated using discrimination, calibration, precision-recall characteristics, clinical utility, and risk stratification metrics, with subgroup analyses across age, sex, and race to assess generalizability. Model interpretability was examined using complementary representation and attention-based frameworks. Results: In 458,884 patients, the survival model demonstrated strong and stable discrimination across cohorts, with overall C-indices of 0.971 (95% CI, 0.965-0.976) in SHZS, 0.945 (95% CI, 0.938-0.950) in SHTP, and 0.855 (95% CI, 0.850-0.860) in BIDMC, and consistently high time-dependent AUROC values across the 1-5-year horizons. Calibration showed close agreement between predicted and observed risks, and decision curve analyses indicated meaningful net clinical benefit across a broad range of thresholds. Kaplan-Meier curves showed clear stratification across predicted risk groups. Interpretability analyses identified physiologically coherent ECG features related to QRS duration, heart rate, and QT interval that were associated with predicted risk. Conclusion: This ECG-based deep learning survival model provides individualized, time-resolved, and clinically interpretable estimates of future HFrEF risk with robust performance across multinational cohorts. These findings support the potential of AI-enabled ECG analysis as an accessible tool for early HFrEF risk stratification within routine clinical workflows.

Background and Objective: Indications for right ventricular assist device (RVAD) insertion include right heart failure after implantation of a left ventricular assist device or early graft failure following heart transplantation. This study aimed to investigate how the upstream and downstream circulatory network interacts with the Impella RP(R) device. Methods: A numerical model of the Impella RP(R) was implemented within CARDIOSIM(C) software platform for this study. In the numerical configuration, the RVAD aspirated blood from either the right atrium (RA-PA connection) or the right ventricle (RV-PA connection) and delivered it to the pulmonary artery. Only RA-PA connection is the currently used setting for Impella RP(R) in clinical practice. Based on right ventricular (RV) decompression and total flow, our study may help define the need for a direct RV-unloading Impella RP(R). Results: The simulations showed that activating the RVAD in RA-PA mode, regardless of its rotational speed, the mean pulmonary artery pressure (PAP) percentage change was higher than the unsupported condition when the mean systemic venous pressure (SVP) and the pulmonary artery wedge pressure (PAWP) were both set to 20 mmHg. When RV-PA connection was applied, a similar trend was observed although the PAP percentage changes were about halved compared to the RA-PA connection. Conclusions: The Impella RP(R) has the potential to become a valid option for RV support based on current experimental and simulation data. Although already in use, further evaluation in the clinical setting will likely confirm its potential and lead to a more routinely application for RV support.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome comprising multiple pathophysiological phenotypes. HFpEF trials have largely enrolled diverse populations and reported average treatment effects, consistently yielding neutral results that may obscure drug-specific benefits within distinct subgroups. To address this issue, we employ an interaction-based that incorporates treatment-by-variable interactions to uncover drug-specific responses. Methods: We leveraged four HFpEF clinical trials (TOPCAT, RELAX, NEAT-HFpEF, INDIE-HFpEF) and developed a framework comprising two complementary approaches. The first employed a prognostic responder model to evaluate whether conventional responder definitions reflect treatment-specific benefit or instead capture favorable clinical trajectories common to both treatment and placebo groups. The second used an interaction-based individual treatment effect (ITE) modeling to identify baseline variables that modify therapy effect, distinguishing drug-specific response from prognostic phenotypes. Results: Although the prognostic responder model demonstrated good discrimination, further analisys suggested it primarily captured a prognostic signal associated with favorable clinical trajectories common to both treatment and placebo arms. In contrast, the ITE model identified distinct, drug-specific effect modifiers across trials (cardiorenal-inflammatory for spironolactone (TOPCAT), NO-mediated anti-inflammatory for isosorbide mononitrate (NEAT-HFpEF), afterload-reducing for inorganic nitrite (INDIE-HFpEF), and anti-volume-overload for sildenafil (RELAX). Each ITE model demonstrated significance only within its own trial suggesting drug-specific signal. Conclusions: The proposed method identifies mechanism-specific effect modifiers, and uncovers clinically meaningful heterogeneity in treatment response, which is not captured by conventional MCID-based approaches. Although exploratory, these findings support phenotype-guided therapy in HFpEF and argue for phenotype-informed trial design to enhance treatment-effect detection and therapy targeting.

Background: Apical sparing of left ventricular longitudinal strain (LS) is an echocardiographic clue to cardiac amyloidosis but may also occur in hypertensive heart disease (HHD). Objectives: To determine whether apical sparing in HHD is associated with regional left ventricular wall stress estimated according to Laplace's law. Methods: We retrospectively studied 1,559 patients with HHD, 47 with light-chain cardiac amyloidosis (ALCA), and 409 normotensive controls. Artificial intelligence-assisted echocardiography quantified segmental LS, wall thickness, and cavity radius at the basal, midventricular, and apical levels. Wall stress was estimated as mean blood pressure (MBP) x radius/(2 x wall thickness). Apical sparing was defined as a relative regional strain ratio (RRSR)[&ge;]1.0. Results: Apical sparing was present in 14 patients with HHD (0.9%), 13 with ALCA (27.7%), and no controls. Among HHD patients with apical sparing, RRSR decreased from 1.11{+/-}0.13 to 0.72{+/-}0.10 after antihypertensive treatment (P<0.001), accompanied by reduced wall stress and improved basal and midventricular LS, with resolution of apical sparing in all 14 patients. In the overall HHD cohort, changes in MBP and left ventricular mass index were independently associated with changes in RRSR. In an exploratory analysis of HHD patients with apical sparing, a reduction in basal wall stress was associated with a reduction in RRSR ({beta}=0.267 for {bigtriangleup}RRSRx100, 95% CI 0.023-0.511; P=0.036). In ALCA, favorable hematologic response was the only determinant of RRSR reduction. Conclusions: Apical sparing in HHD was uncommon but reversible and may represent a load-sensitive deformation pattern associated with regional wall stress, consistent with Laplace's law.