Right Heart Failure Research Articles

Abstract 4116410: A Novel Deep Learning Approach for Prediction of Right Heart Failure After Left Ventricular Assist Device Implantation using Pulmonary Artery Pressure Tracings

Introduction: Left ventricular assist device (LVAD) offers a lifeline for advanced heart failure patients, but ~30% experience post-operative right heart failure (RHF) with significant morbidity and mortality. Current methods for predicting RHF risk have limited accuracy. This study is the first of its kind to explore the feasibility of using a convolutional neural network (CNN) deep learning model with pulmonary artery pressure (PAP) tracings acquired during pre-operative hemodynamic assessment to identify patients at risk for early RHF. Methods: A CNN model was pre-trained on PAP tracings from the MIMIC-III Waveform Database to leverage transferable knowledge and improve model performance. The model learned general features and temporal relationships in hemodynamic tracing morphology for RHF prediction. It was then adapted for classification by modifying the output layers. Post-LVAD RHF was definitively adjudicated for each instance included from our 246 patient single center LVAD database. RHF was adjudicated using the 2020 Academic Research Consortium defintion. The database included 205 non-RHF instances and 41 RHF instances. We developed a novel signal processing method utilizing computer vision to extract PAP waveform data from pre-operative right heart catheterization reports. Data was reviewed to ensure accurate pressure tracing representation. SMOTE-ENN (synthetic oversampling) and class weighting addressed dataset imbalance during training to enhance model generalizability and RHF prediction accuracy. Results: The model achieved strong performance in classifying RHF from non-RHF outcomes, as evidenced by consistent AUC scores of 0.87 and 0.85 on validation and unseen test data, respectively. These findings indicate the potential for hemodynamic tracings to predict RHF after LVAD implantation. Notably, the model maintained its performance on unseen data, highlighting its generalizability. Conclusions: This study explored the feasibility of using a deep learning model for RHF risk stratification in patients with LVADs. The model, pre-trained on PAP tracings, achieved promising classification performance assessed by AUC. Further validation with larger, more diverse datasets will refine model performance and enhance generalizability for clinical application. Leveraging hemodynamic tracings within a deep learning framework holds promise for improved clinical outcome prediction.

Abstract 4138475: Comparative Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement in Patients with Right Heart Failure: Insights from Nationwide Readmission Database

Background: The annual number of transcatheter aortic valve implantation (TAVI) performed has surpassed that of surgical aortic valve replacement (SAVR) as its use expands to patient populations not included in initial clinical trials. However, in patients with Right Heart Failure (RHF), the outcomes of TAVI and SAVR remain unclear. Methods: We conducted a retrospective cohort study using the Nationwide Readmission Database from 2018 to 2021. Using ICD-10 codes, we identified all adult admissions for TAVI and SAVR with the presence of RHF. The primary outcome was in-hospital mortality. Secondary outcomes included in-hospital complications, 30-day readmission rate, length of stay, and total hospitalization charges. Results: The study included 3,712 adult patients with RHF, of which 1,386 (37.3%) underwent TAVI and 2,326 (62.7%) underwent SAVR. Compared to SAVR patients, TAVI patients were older (63 years vs. 76 years, p<0.01) and had a higher burden of peripheral vascular disease, chronic liver disease, and coagulopathy, while SAVR patients had a higher burden of hypertension, diabetes mellitus, coronary artery disease, left heart failure, chronic lung disease, smoking, malignancy, and anemia. On multivariable analysis, compared to TAVI, SAVR was associated with higher odds of mortality (26.6% vs. 9.3%, p<0.01), mechanical circulatory support use (41.5% vs. 9.22%, p<0.01), respiratory failure (34.2% vs. 10.2%, p<0.01), acute kidney injury (58.1% vs. 37.7%, p<0.01), and need for blood transfusion (31.4% vs. 11.0%, p<0.01). There was no difference in 30-day readmission (13.8% vs. 14.3%, p=0.51) and permanent pacemaker implantation (7.0% vs. 8.7%, p=0.33). SAVR was associated with a longer median hospital stay (14 days vs. 8 days, p<0.01) and higher hospitalization charges ($406,826 vs $265,303, p<0.01). When compared to patients wihout RHF, the presence of RHF predicted higher in-hospital mortality for both TAVI (9.3% vs. 1.2%, p<0.01) as well as SAVR (26.6% vs. 3.7%, p<0.01). Conclusions: From 2018 to 2021, more RHF patients underwent SAVR (62.7%) than TAVI (37.3%), but SAVR was associated with worse short-term outcomes, including higher in-hospital mortality, in-hospital complications, and healthcare resource utilization.

Abstract 4138674: Long-acting CRF2 receptor agonist, COR-1389, improves cardiopulmonary function in the rat model of Sugen plus hypoxia-induced pulmonary hypertension and right heart failure

Introduction: Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use. Hypothesis: In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF). Methods: To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry. Results: Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups. Conclusion: These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.

The hemodynamic classification system for hemodynamic-related adverse events in left ventricular assist device patients

Abstract Background Durable left ventricular assist device (LVAD) physiology predisposes to right heart failure (RHF) and aortic insufficiency (AI), recently labelled hemodynamic-related adverse events (HDREs). However, the pathophysiology, incidence, and associated morbidity of HDREs remains largely unsettled due to heterogeneity in data reporting. Purpose We sought to validate the recently proposed LVAD Hemodynamic Classification System (HCS) for HDREs. Methods RHF and AI HDREs were retrospectively adjudicated, staged (mild to severe) and phenotyped (isolated or combined RHF/AI-HDREs) based on the HCS assessed at 6-month post-LVAD implant among 183 consecutive patients undergoing LVAD implant at a quaternary heart failure center, and either alive at 6-month on support (n=175) or deceased due to late HDREs 1 to 6 months post-LVAD implant (n=8). The primary outcome was a composite of first HF hospitalization or cardiovascular death between 6 and 24 months after LVAD-implant. Results At 6-month assessment, RHF-HDRE was adjudicated in all patients, while AI-HDRE could not be adjudicated in 22 (12.0%) patients. Overall, 53 (29.0%) patients developed an RHF-HDRE, and 26 (16.0%) an AI-HDRE (phenotypes: 39 isolated RHF, 15 isolated AI, 11 combined RHF-AI, 3 not-adjudicated). During pre-LVAD assessment, age and pulmonary artery pulsatility index were independently associated with RHF-HDRE; and pre-LVAD AI and systolic pulmonary artery pressure with AI-HDRE. Patients developing the combined RHF-AI phenotype required the most intensive bundle of critical care pre-LVAD implantation, had more frequent pre-LVAD RV dysfunction, the highest rate of early post-LVAD RHF, and the most prominent features of suboptimal left ventricular unloading, RV dysfunction, peripheral congestion, renal damage and impaired functional capacity at 6-month assessment. RHF-HDRE (adj-HR 2.69, 95%CI 1.14-6.34, p=0.024), AI-HDRE (adj-HR 4.21, 95%CI 1.70-10.40, p=0.002) and HDRE phenotype (isolated RHF or AI HDRE vs. no HDRE: adj-HR 2.80, 95%CI 1.03-7.62, p=0.044; combined RHF and AI HDRE vs. no HDRE: adj-HR 4.53, 95%CI 1.33-15.35, p=0.015) were associated with the primary outcome. A graded increase in primary outcome was observed with rising RHF and AI stages. Conclusions The LVAD Hemodynamic Classification System for HDREs identifies pathophysiological and clinical clusters of patients with significant prognostic implications. It may help the development of targeted strategies to mitigate HDREs and improve the success of long-term LVAD support.

Long-acting CRF2 receptor agonist COR-1389 improves cardiopulmonary function parameters in monocrotaline-induced pulmonary hypertension and right heart failure rat model

Abstract Background Pulmonary hypertension (PH) associated with right heart failure (RHF) poses a significant therapeutic challenge. Short term studies have shown that urocortin-2 (UCN-2) administration, either intravenously or subcutaneously, can ameliorate cardiac and/or pulmonary parameters in human heart failure (HF) and in animal models of PH and RHF. Purpose This study aimed to evaluate the potential benefits of COR-1389, a long-acting CRF2 receptor agonist, on cardiopulmonary function and adverse remodeling in a rat model of monocrotaline (MCT)-induced PH and RHF. Method Monocrotaline (40 mg/kg) was administered subcutaneously in rats on Day-0 to induce PH and RHF, while the control group received vehicle. After 14 days, MCT-injected rats were evenly allocated into two groups based on echocardiography parameters of accelerated time/ejection time ratio and tricuspid annular plane systolic excursion (TAPSE), before receiving either COR-1389 (100 ug/kg) or its vehicle subcutaneously every 4 days for 14 days. On Day-28, echocardiography was repeated in all groups, followed by right heart catheterization to directly measure pulmonary hemodynamics. Heart and lung samples were prepared for histological analysis. Results By Day-28, MCT-treated rats exhibited significantly elevated mean pulmonary arterial pressure (mPAP) and right ventricular (RV) mass (Fulton Index/BW), along with decreased RV function (increased TAPSE) and reduced cardiac output (CO) compared to control rats. These changes were accompanied by severe tissue remodeling, including increased vascular muscularization (alpha-smooth muscle actin content) and pulmonary arterial wall thickening, RV fibrosis, and cardiomyocyte hypertrophy. Following 14 days of curative treatment, MCT+COR-1389 compared to MCT, significantly decreased mPAP and RV mass (Fulton Index/BW), while RV function improved (reduced TAPSE) and CO was increased. Moreover, COR-1389 attenuated adverse pulmonary vascular remodeling (reduced muscularization and arterial wall thickening), RV fibrosis, and cardiomyocyte hypertrophy, consistent with its hemodynamic effects. Conclusions Chronic CRF2 agonism with COR-1389 improved dysregulated cardiac and pulmonary function and structure in the MCT rat model, suggesting its potential for the treatment of PH and RHF.

CMR predictors of acute right heart failure after LVAD implantation

Abstract Background Acute right heart failure (RHF) is one of the most dangerous complications after placement of left ventricular assisted device (LVAD), having a significant impact on prognosis, and is estimated to be around 3 to 35%. Even though right ventricular evaluation with hemodynamical and echocardiographic measurements is a key aspect prior to LVAD implantation, prediction of RHF remains a challenge in daily clinical practice. Purpose To identify cardiac magnetic resonance (CMR) predictors of RHF after LVAD placement. Methods We retrospectively enrolled patients referred to our centre for implantation who also underwent CMR scan prior to LVAD implantation. Acute RHF was defined according to Mechanical Circulatory Support Academy Research Consortium (MRC ARC) criteria. Baseline characteristics, preoperative laboratory, echocardiographic, right heart catheterization (RHC) and CMR parameters were obtained. Patients were divided into two groups based on the development of acute RHF. The variables showing significant differences between the two groups were analysed with the receiver operating characteristic (ROC) curves to find the best cut-offs and then combined into a risk score. Results We enrolled 54 patients who underwent continuous-centrifugal flow LVAD implantation from 2013 to 2021 in whom a CMR within median time of 30 days pre-implantation was available. Four patients were excluded due to low quality images. Among the final cohort of 50 patients, 15 (28%) developed acute RHF. Patients who developed RHF showed worse INTERMACS class, worse renal and liver function, higher central venous pressure at RHC, worse TAPSE at echocardiography and overall smaller left ventricles at the CMR analysis when compared to those who had not acute RHF. No CMR derived right ventricle parameters nor moderate to severe tricuspid regurgitation at echocardiography were different among the two groups. We found that CMR-derived LV mass indexed < 65 g/m2, left ventricular end diastolic diameter (LVEDD) < 70 mm, and LV eccentricity index >1,12 were independent predictors of acute RHF. A CMR-derived score with these three parameters was built (1 point for each). This CMR score has shown to be an independent predictor of acute RHF at multivariate analysis with an odds ratio of 7,084 (CI 95%1.614-37.734) when corrected for other clinical and instrumental predictors of acute RHF. Conclusions Our study proposes a simple scoring system based on three CMR- derived parameters (LVEDD, LV mass indexed and LV eccentricity index) to screen for acute RHF prior LVAD implantation. This score shows promise to be an independent predictor of acute RHF, even when adjusted for clinical, echocardiographic, and haemodynamic parameters. Our model is built on CMR measurement of the LV, showing how patients with smaller ventricles and a left displacement of the interventricular septum (expressed with a higher LV eccentricity index) are at higher risk of developing acute RHF.ROC curves

A new right-heart failure staging system in patients with severe tricuspid regurgitation. Prognostic implications

Abstract Objective Our aim was to describe a new right-heart failure (RHF) staging system in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period, classified according to their clinical condition and right ventricular status, and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. A new RHF staging was proposed depending on clinical condition, RV dilation and RV systolic dysfunction (Table). The largest group of patients had a normal right ventricle with signs/symptoms of RHF (41%). Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the multivariate analysis the predictors of CV mortality were age, impaired renal function, previous HF admission, massive and torrential TR and Stages III and IV of the new right-heart failure staging system (figure). Conclusion The new RHF staging system accurately stratifies patients with severe TR into prognostic categories.

Ferroptosis Inhibition Combats Metabolic Derangements and Improves Cardiac Function in Pulmonary Artery Banded Pigs.

Right heart failure (RHF) is a leading cause of mortality in multiple cardiovascular diseases and preclinical and human data suggest impaired metabolism is a significant contributor to right-sided cardiac dysfunction. Ferroptosis is a nonapopotic form of cell death driven by impaired metabolism. Rodent data suggests ferroptosis inhibition can restore mitochondrial electron transport chain function and enhance cardiac contractility in left heart failure models, but the effects of ferroptosis inhibition in translational large animal models of RHF are unknown. Here, we showed ferrostatin-1 mediated ferroptosis antagonism improve right heart structure and function in pulmonary artery banded pigs. Molecularly, ferrostatin-1 restored mitochondrial cristae structure and combatted downregulation of electron transport chain proteins. Metabolomics and lipidomics analyses revealed ferrostatin-1 improved fatty acid metabolism. Thus, these translational data suggest ferroptosis may be a therapeutic target for RHF.

The effects of sodium-glucose cotransporter 2 inhibitors on the 'forgotten' right ventricle.

With the progress in diagnosis, treatment and imaging techniques, there is a growing recognition that impaired right ventricular (RV) function profoundly affects the prognosis of patients with heart failure (HF), irrespective of their left ventricular ejection fraction (LVEF). In addition, right HF (RHF) is a common complication associated with various diseases, including congenital heart disease, myocardial infarction (MI), pulmonary arterial hypertension (PAH) and dilated cardiomyopathy (DCM), and it can manifest at any time after left ventricular assist devices (LVADs). The sodium-glucose cotransporter 2 (SGLT2) inhibition by gliflozins has emerged as a cornerstone medicine for managing type 2 diabetes mellitus (T2DM) and HF, with an increasing focus on its potential to enhance RV function. In this review, we aim to present an updated perspective on the pleiotropic effects of gliflozins on the right ventricle and offer insights into the underlying mechanisms. We can ascertain their advantageous impact on the right ventricle by discussing the evidence obtained in animal models and monumental clinical trials. In light of the pathophysiological changes in RHF, we attempt to elucidate crucial mechanisms regarding their beneficial effects, including alleviation of RV overload, reduction of hyperinsulinaemia and inflammatory responses, regulation of nutrient signalling pathways and cellular energy metabolism, inhibition of oxidative stress and myocardial fibrosis, and maintenance of ion balance. Finally, this drug class's potential application and benefits in various clinical settings are described, along with a prospective outlook on future clinical practice and research directions.

8527 The Role Of SGLT2 Inhibitors In Outcomes After LVAD Implantation

Abstract Disclosure: L. Carafone: None. S. McNitt: None. I. Goldenberg: None. J. Alexis: None. Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important medications in the treatment of diabetes mellitus, however they offer several additional benefits, including improved heart failure outcomes in patients with and without diabetes. The role of SGLT2i in heart failure outcomes for patients who receive left ventricular assist device (LVAD) implantation is not known. Right heart failure, in particular, is a frequent complication and major contributor to morbidity and mortality after LVAD implantation. SGLT2i have been increasingly used in patients who undergo LVAD implantation, however it is unknown whether right heart failure events post-LVAD implantation are meaningfully impacted by SGLT2i use. Objective: The purpose of this study was to evaluate the role of SGLT2i in outcomes after LVAD implantation. The primary endpoint was the onset of a first right heart failure (RHF) event following LVAD implantation. Secondary endpoints included recurrent RHF, first and recurrent hospitalization for RHF, and all-cause mortality. Methods: The study population comprised all consecutive patients who received a HeartMate 3 LVAD implantation at the medical center from 9/25/2015 through 9/1/2023 who are included in the institution’s LVAD Database. Both patients who received and did not receive a SGLT2i were included. A time-dependent model was used to evaluate treatment with SGLT2i as a time-dependent variable. Multivariable propensity score matching was used in the analysis of outcomes. Results: A total of 399 patients were analyzed, which included 175 patients who received SGLT2i and 224 patients who did not receive SGLT2i. Cox proportional hazards regression, employing propensity score stratification, demonstrated SGLT2i use was not associated with a statistical significant effect in the primary endpoint of a first occurrence of RHF event (HR = 1.41, 95% CI = 0.77-2.61, p = 0.268). Similarly, SGLT2i use was not associated with secondary outcomes, including recurrent RHF (HR = 1.28, 95% CI = 0.76-2.16, p = 0.360), first or recurrent hospitalization for RHF (HR = 0.38, 95% CI = 0.11-1.33, p = 0.131 and HR = 0.63, 95% CI = 0.27-1.46, p = 0.285, respectively), and all-cause mortality (HR = 0.90, 95% CI = 0.44-1.83, p = 0.771). Presence or absence of diabetes diagnosis did not significantly impact outcomes. Conclusions: The observational data in this study suggest no incremental benefit of SGLT2i for right heart failure or mortality outcomes after LVAD implantation, however large-scale prospective studies are needed to evaluate the role of SGLT2i in this setting. Further elucidating the role of these medications in LVAD outcomes will be critical in clinical decision-making regarding use of SGLT2i in this population. Presentation: 6/1/2024

The Right Ventricular-Arterial Compliance Index: A Novel Hemodynamic Marker to Predict Right Heart Failure Following Left Ventricular Assist Device.

The development of right heart failure (RHF) in patients with advanced heart failure following left ventricular assist device (LVAD) implantation remains difficult to predict. We proposed a novel composite hemodynamic index-the right ventricular-arterial compliance index (RVACi), derived from pulmonary artery pulse pressure (PAPP), ejection time (ET), heart rate (HR), and cardiac output (CO), with and expressed as mm Hg·s/L. We then conducted a retrospective, single-center analysis comparing the predictive value of RVACi for the development of RHF or unplanned right ventricular (RV) mechanical circulatory support following LVAD implantation against existing hemodynamic indices. One hundred patients were enrolled after screening 232 patients over a 10 year period, with 74 patients having complete hemodynamic data for RVACi calculation. There was good correlation between pulmonary arterial capacitance (R² = 0.48) and pulmonary vascular resistance (R² = 0.63) with RVACi, but not RV stroke work index or pulmonary artery pulsatility index. Reduced baseline RVACi (52 ± 23 vs. 92 ± 55 mm Hg·s/L; p = 0.02) was the strongest hemodynamic predictor of unplanned RV mechanical circulatory support requirement in patients following LVAD insertion. Composite pulsatile hemodynamic indices including RVACi may provide additional insight over existing hemodynamic indices for the prediction of RHF and need for RV mechanical circulatory support.

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia using Pulmonary Artery Banding.

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.

Recurrent Infected Bronchiectasis in Poorly Controlled Patient Leading to Cardio Hepatorenal Syndrome

Background: Cardio hepatorenal syndrome is a severe condition due to chronic congestive heart failure complications characterized by liver and kidney function impairment, however, this condition has a potentially reversible complication.Bronchiectasis as a chronic lung disease was a burden for the healthcare system, especially involving other organs like heart, liver, and renal function. Those conditions were complicated and created a quandary regarding the effective treatments to improve the clinical condition and reduce morbidity and mortality. Case illustration: A 42-year-old man developed cardio hepatorenal syndrome (CHRS), which may have occurred from recurrent infected bronchiectasis that he had. His HRCT scan of the thorax with contrast showed multiple dilated bronchiwith tram track and signet ring appearance with decreased liver and renal function in laboratory findings, and probability of pulmonary hypertension (PH) and right heart failure (RHF) in echocardiography examination. The diuretic, beta-blocker, and antibiotics were given. During hospitalization, there was improvement day by day not only in his clinical condition but also in his liver and renal function. He has used oxygen as needed, and there was no longer any indication for him to be hospitalized. Conclusion: Patients with chronic lung diseases like bronchiectasis could have decreased lung function, which developed into other connected organ functions, like heart, liver, and renal. In this case, we found reduced heart, liver, and renal function, requiring a multidisciplinary approach to improve the condition.

Dapagliflozin alleviates right heart failure by promoting collagen degradation by reducing ROS levels

BackgroundRight ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms. MethodsWe conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-β) to investigate the effect of DAPA. ResultsIn vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels. ConclusionsIn summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF.

Abstract Mo041: Bile Acid Dysregulation in Response to Right Heart Failure and Hepatic Congestion

Introduction: Right heart failure (RHF), the result of impaired RV contractility and/or severe right-sided valvulopathies, is a clinical syndrome that commonly results in chronically elevated central venous pressures and hepatic congestion. Hepatic dysfunction in patients with heart failure portends a poor prognosis. In part, this may be due to the liver’s pivotal role in bile acid synthesis and processing. In addition to the classic role of a digestive surfactant, bile acids serve as important and dynamic signaling molecule. The present study characterizes a unique bile acid profile found in patients with RHF. Research Question: We hypothesize that RHF and hepatic congestion results in a dysregulation of bile acids. These untoward changes in bile acids concentrations may provide both important prognostic value and novel mechanistic pathways in congestive liver disease. Aims: 1) To characterize systemic and hepatic vein bile acid concentrations in patients with right heart failure. 2) To phenotype a mouse model of hepatic congestion and understand the mechanistic effects of specific bile acids on liver biology Methods: We enrolled a total of 60 patients who were referred for right heart catheterization (RHC). Patient demographics, echocardiograms, and routine laboratory tests were captured at enrollment. Blood was sampled from the IVC and hepatic vein during RHC. Bile acids were quantified from serum using liquid chromatography-tandem mass spectrometry. To model hepatic congestion, mice underwent ligation of the IVC. Blood and tissue samples were harvested and underwent mass spectrometry evaluation for the bile acid composition and immunohistochemistry was performed to characterize the immune landscape, respectively. Results: We captured a total of 12 control samples from patients with normal filling pressures, 25 patients with left heart failure (LHF), and 23 patients with RF. Patients with RHF had poorer survival outcomes compared to control or LHF. Patients with RHF had significant increases in specific conjugated bile acids when compared to control or LHF (Figure 1). Conclusions: In this study, we identified several conjugated bile acids that are uniquely elevated in patients with RHF compared to LHF and control. Additionally, patients with RHF had poorer survival. Collectively, these data suggest bile acids may serve as important biomarkers and signaling molecules in the pathogenesis of cardiogenic liver disease.

Galectin-3 as a Prognostic Biomarker of Left Ventricular Assist Device Implantation Outcomes.

We assessed the prognostic potential of Galectin-3 in a sample of 159 heart failure patients who received a left ventricular assist device (LVAD) implant from 2012 to 2020. Clinical outcomes included hemodynamic data, right heart failure (RHF), hemocompatibility-related adverse events (HRAEs), and mortality. Galectin-3 was compounded into Michigan-RVF and EUROMACS-RHF risk scores and compared to the noncompounded risk scores. Right heart failure was significantly correlated with Galectin (p = 0.004) on a continuous spectrum. Inotrope duration was significantly correlated to Galectin-3 (interquartile range [IQR]: 7.58-8.65, p < 0.001) along with INTERMACS score (IQR: 2.14-1.90, p < 0.001). Intensive care unit length of stay (median 8 days, p = 0.02), blood urea nitrogen (p < 0.001), creatinine (p < 0.001), and pulmonary artery pulsatility index (p = 0.05) were also significantly correlated with Galectin-3. In our c-statistic analysis, the predictive value for RHF improved when Galectin-3 was included for both the Michigan-RVF (0.80-0.86) and EUROMACS-RHF (0.77-0.82) risk scores. When elevated over a binary cutoff of 18.2 ng/ml, Galectin-3 significantly correlated with HRAEs (p = 0.014) and mortality (p = 0.031). Galectin-3 shows great promise as a predictive biomarker in patients implanted with durable LVADs. In addition to significant correlation with key clinical outcomes, Galectin-3 enhanced the Michigan-RVF and EUROMACS-RHF risk scores in predicting progression to RHF.

Abstract Tu037: Unraveling the Cellular Mechanisms of Cardiogenic Liver Disease

Background: Right heart failure (RHF) is associated with chronically elevated central venous pressures which can lead to hepatic dysfunction, fibrosis, and ultimately cirrhosis. Despite the prognostic importance of liver disease in RHF little is understood about the cellular and molecular changes that define cardiogenic liver disease. Filling this knowledge gap has the potential to lead to better diagnostic and therapeutic approaches for patients with heart failure and liver dysfunction. Aims: 1) To evaluate the key clinical and pathologic features of cardiogenic liver disease in humans 2) To explore shifts in the cellular landscape in the congested liver using human samples and a mouse model congestive hepatopathy. Methods: We identified 34 patients with heart failure who underwent liver biopsy due to concern for cardiogenic liver disease. These biopsy samples were stained for numerous cellular markers (macrophage subsets, activated stellate cells, endothelial cells, biliary cells) and compared to normal controls. Clinical data was also collected for the included patients. To model cardiogenic liver disease in a mouse we performed partial IVC ligation (pIVCL) to induce liver congestion and then assessed the liver response using flow cytometry, tissue imaging and mRNA analysis. Results: Liver biopsies from patients with cardiogenic liver disease demonstrated increased liver fibrosis, macrophage aggregates, and biliary metaplasia. The severity of biliary metaplasia was closely associated with the extent of liver congestion. Using multi-marker staining the metaplastic cells were found to be of hepatocyte origin. Interestingly, the liver niche containing metaplastic biliary cells was also enriched for recruited macrophages and activated stellate cells. Similar pathologic features were observed in the mouse model of liver congestion. Conclusions: In this study we identified biliary metaplasia and macrophage recruitment as key pathologic features of cardiogenic liver disease. Ongoing investigation of the interplay between macrophages and metaplastic biliary in humans and animal models of congestive hepatopathy may lead to the discovery of novel disease mechanisms and biomarkers for liver dysfunction in heart failure.

Perioperative and intermediate outcomes of patients with pulmonary embolism undergoing catheter-directed thrombolysis vs percutaneous mechanical thrombectomy

ObjectiveThrombolytic therapy has been a mainstay of treatment for massive or submassive pulmonary embolism (PE), a common and highly morbid pathology. New percutaneous mechanical thrombectomy (PMT) devices have recently become widely available and have been used increasingly for the treatment of acute PE, but evidence demonstrating its efficacy over standard catheter-directed lytic protocol remains limited. MethodsUsing TriNetX Data Network, a global federated database of >250 million patients, we conducted a retrospective cohort study of patients from January 2017 to August 2023 with a diagnosis of PE, treated with either PMT or catheter-directed thrombolysis (CDT). Eligible patients were 1:1 propensity score-matched for preoperative covariates including demographics and comorbidities. We calculated and compared the 30-day outcomes of all-cause mortality, bleeding complications (blood transfusion, gastrointestinal bleed, and intracranial hemorrhage), diagnosis of acute respiratory failure (RF), myocardial infarction (MI), and pulmonary hypertension (PH) using odds ratios (OR) with 95% confidence intervals (CIs). Also, the 5-year outcomes of all-cause mortality, a composite outcome of chronic PH (chronic PE, chronic cor pulmonale, chronic thromboembolic PH), right heart failure (RHF), RF, and emergency department visits, were compared using hazard ratios (HRs) with 95% CIs. ResultsWe identified 2978 patients treated with PMT and 1137 patients treated with CDT. After matching, we compared 1102 patients in each cohort. For 30-day outcomes, all-cause mortality, acute RF, and blood transfusion were similar between the two groups. However, compared with CDT, PMT was associated with a better safety profile, including lower bleeding risk for both ICH (OR, 0.46; 95% CI, 0.24-0.890) and gastrointestinal bleed (OR, 0.42; 95% CI, 0.28-0.63). PMT also demonstrated better immediate functional outcomes, with less PH (OR, 0.53; 95% CI, 0.41-0.68) and MI (OR, 0.54; 95% CI, 0.41-0.76). At 5 years, the all-cause mortality and RF for both procedures were similar, but PMT was associated with lower rates of chronic PH (HR, 0.70; 95% CI, 0.55-0.90), RHF (HR 0.49; 95% CI, 0.37-0.65), and emergency department visits (348 for PMT vs 426 for CDT; P < .01). ConclusionsIn patients undergoing catheter-based therapy for PE, PMT has an improved procedural safety profile vs CDT and results in significantly fewer 30-day postoperative complications, with fewer bleeding events, and is also associated with fewer periprocedural MIs and less acute PH. Perhaps, more important, PMT also demonstrated improved long-term outcomes with significantly fewer chronic PH and RHF diagnoses with fewer emergency department visits.

Concomitant tricuspid valve surgery in patients with significant tricuspid regurgitation undergoing left ventricular assist device implantation: A systematic review and meta-analysis.

Significant tricuspid regurgitation (TR) is a predictor of right heart failure (RHF) and increased mortality following left ventricular assist device (LVAD) implantation, however the benefit of tricuspid valve surgery (TVS) at the time of LVAD implantation remains unclear. This study compares early and late mortality and RHF outcomes in patients with significant TR undergoing LVAD implantation with and without concomitant TVS. A systematic search of four electronic databases was conducted for studies comparing patients with moderate or severe TR undergoing LVAD implantation with or without concomitant TVS. Meta-analysis was performed for primary outcomes of early and late mortality and RHF. Secondary outcomes included rate of stroke, renal failure, hospital and ICU length of stay. An overall survival curve was constructed using aggregated, reconstructed individual patient data from Kaplan-Meier (KM) curves. Nine studies included 575 patients that underwent isolated LVAD and 308 patients whom received concomitant TVS. Both groups had similar rates of severe TR (46.5% vs. 45.6%). There was no significant difference seen in risk of early mortality (RR 0.90; 95% CI, 0.57-1.42; p = 0.64; I2 = 0%) or early RHF (RR 0.82; 95% CI, 0.66-1.19; p = 0.41; I2 = 57) and late outcomes remained comparable between both groups. The aggregated KM curve showed isolated LVAD to be associated with overall increased survival (HR 1.42; 95% CI, 1.05-1.93; p = 0.023). Undergoing concomitant TVS did not display increased benefit in terms of early or late mortality and RHF in patients with preoperative significant TR. Further data to evaluate the benefit of concomitant TVS stratified by TR severity or by other predictors of RHF will be beneficial.

Right Ventriculoarterial Coupling Surrogates and Long-Term Survival in LVAD Recipients: Results of the ASSIST-ICD Multicentric Registry

Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.