Outcomes In Advanced Heart Failure Research Articles

MELD score predicts outcomes in patients with advanced heart failure: A longitudinal evaluation.

Advanced heart failure (AHF) is characterized by recurrent episodes of haemodynamic instability and frequent hospitalizations, leading to a progressive decline in quality of life and high mortality rates. The objectives of this study were to evaluate the effect of the model for end-stage liver disease (MELD) score and its variations in predicting adverse outcomes [death, urgent heart transplant, and left ventricular assist device (LVAD) implant] among patients with AHF to assess the clinical associations of the MELD score in this population and to compare the efficacy of this tool with other prognostic scores in AHF. In this longitudinal prospective study, 162 patients with advanced heart failure (AHF) were enrolled; all patients included in the study were receiving the maximum tolerated medical therapy according to guidelines. The MELD score was measured at baseline and every 6months during follow-up. All patients underwent echocardiographic assessment and cardiopulmonary testing, which included the evaluation of maximal oxygen uptake (VO2max) and the minute ventilation/carbon dioxide production (VE/VCO2) slope. The mean age of the study group was 57.7±11.6years. There were 26 deaths, 5 urgent transplants, and 1 LVAD implantation during a follow-up period of 31.4±15.6months. The mean New York Heart Association (NYHA) class was 2.8±0.5, ejection fraction (EF) was 26.3±6.5%, the mean VO2max was 11.7±3.5mL/kg/min. Multiple regression analysis revealed a positive correlation between the MELD score and NT-proBNP (β=0.215; P=0.041) and furosemide dosage (β=0.187; P=0.040). Conversely, a negative correlation was observed between the MELD score and TAPSE (β=-0.204; P=0.047). Multivariate Cox regression on combined outcome shows a HR of 1.094 (95% CI 1.003-1.196) for unit increase in MELD considered as a continuous variable. The predictive role is independent by the effect of covariates considered in the analysis such as age, sex, NYHA class, EF, TAPSE, PASP, VO2max, NT-proBNP, MELD score worsening, and NT-proBNP increase. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality, urgent heart transplant and LVAD implant. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.887 for MELD score and composite outcome of death, urgent transplant, and need for LVAD. The predictive performance of MELD was even superior compared with MELD-Na, MELD-XI, MAGGIC risk score, and MECKI. The MELD score and its longitudinal changes are effective predictors of adverse outcomes in AHF.

Cardiac power output associated with hospitalization and mortality in coronary artery disease patients at stage B heart failure

BackgroundCardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. MethodsWe conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up. ResultsA total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 – 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 – 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 – 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification. ConclusionResting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management.

Severe obesity among patients with left ventricular assist devices

Patients with obesity and advanced heart failure requiring left ventricular assist device (LVAD) support are more likely to experience LVAD complications and may be disproportionately Black and/or female when compared to patients without obesity. Among these patients, obesity may represent a barrier to transplant eligibility and a marker of inequity in heart transplantation and health outcomes in advanced heart failure. To better understand this issue at our institution, we examined our active LVAD cohort and found that almost one-third of all patients had severe obesity with BMI ≥ 35 kg/m2. Patients with LVADs and severe obesity were significantly younger and more likely to self-identify as Black, and numerically more likely to be female. Weight management in this group represents a vital area for improved equity in health outcomes and barriers to heart transplantation. NA.

Excessive fat expenditure in MCT-induced heart failure rats is associated with BMAL1/REV-ERBα circadian rhythmic loop disruption

Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light–dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light–dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA β oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.

Right ventricular-pulmonary arterial uncoupling and ventricular-secondary mitral regurgitation: Relationship with outcomes in advanced heart failure

BackgroundSecondary mitral regurgitation (MR) is common in heart failure with reduced ejection fraction (HFrEF) and associated with poor outcomes. However, there is little evidence regarding secondary MR in advanced HFrEF. Poor outcomes for MR intervention suggest a need for further risk stratification. ObjectivesWe hypothesized adverse prognosis in right ventricles (RV) less able to compensate for increased pulmonary pressures of post-capillary cause in the context of secondary MR. MethodsPatients were assessed with echocardiography, right heart catheterisation (RHC) and cardiopulmonary exercise testing. Ventricular-secondary MR was identified by echocardiography and categorised mild, moderate, or severe according to guidelines. RV ability to compensate for pulmonary pressure rise was assessed by RV-pulmonary artery (PA) coupling, calculated as ratio of tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) (echocardiography for TAPSE and RHC for SPAP). Primary endpoint was a composite of all-cause mortality, urgent heart transplantation or mechanical circulatory support. Results456 patients with ventricular-secondary MR were followed up for a median of 2.39 years, with 237 reaching a primary endpoint. Severe MR conferred a worse prognosis than mild or moderate (HR 2.6, p<0.001). Right atrial pressure was predictive of survival. RV-PA uncoupling, defined as TAPSE/SPAP below median value of 0.37, was associated with reduced survival across all severities of mitral regurgitation (p<0.001). ConclusionsVentricular-secondary MR is common and severity correlates with adverse prognosis in advanced heart failure. RV-PA uncoupling can improve risk stratification in all grades of MR severity, particularly with PA pressure determined invasively.

Abstract 16829: Systemic Arterial Pulsatility Index Correlates With Long Term Mortality in Cardiogenic Shock

Introduction: Systemic arterial pulsatility index (SAPi) is a marker for ventriculo-arterial coupling that incorporates the contractile properties of the left ventricle with aortic impedance. Prior studies have demonstrated the association of SAPi with adverse outcomes in advanced heart failure. The association of SAPi in cardiogenic shock has not been studied. We evaluated the association of SAPi with mortality in patients with cardiogenic shock with comparison to cardiac output. Methods: Consecutive patients with cardiogenic shock at University of Virginia from 01/2017 to 09/2021 with right heart catheterization data were included in this analysis. Baseline SAPi [systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure] and cardiac output were calculated on admission. Patients were stratified into high and low SAPi based on median SAPi. Cox proportional hazards regression was used to evaluate the association of SAPi stratas with mortality at 1 year. Receiver-operating characteristic (ROC) analysis was performed. Results: Among 120 patients (mean age 55.9, 34.1% female), 40 patients died (33.3%) within 12 months of admission. The median SAPi was 1.96 (IQR 1.25-2.49).Lower values of SAPi were associated with increased mortality at both 1 month (AUC =0.62, p=0.45) and 12 months (AUC =0.63, p=0.02) 12 months mortality with AUC of 0.63 (p=0.02) (Figure 1). The baseline cardiac output was not associated with this survival. Conclusions: In a contemporary cohort of cardiogenic shock patients, low SAPi was associated with increased mortality at both 1 and 12 months after admission for cardiogenic shock and provided better prediction than the baseline cardiac output. Further studies are needed to evaluate the utility of SAPi in hemodynamic monitoring of cardiogenic shock patients. Figure 1

Comparative Analysis of Different Prognostic Markers in Predicting Outcome in Advanced Heart Failure

Introduction: Heart failure (HF) is a debilitating condition with an adverse outcome, especially during the advanced stage having higher morbidity and mortality rates. Various parameters have been used as prognostic markers in advanced HF. This study highlights about the comparative analysis of different prognostic markers in predicting mortality in advanced HF. Methods: This prospective observational study was conducted in patients of advanced HF admitted to the department of medicine intensive care unit in a rural tertiary care hospital from 2018 to 2020. Advanced HF was diagnosed using the updated HF Association-European Society of Cardiology criteria. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk test (6MWT), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate, and glycosylated hemoglobin type A1c levels were measured on admission. Receiver operating characteristic (ROC) curve was also studied for the above-mentioned variables, and the area under ROC curve (AUROC) was also determined. Results: Seventy-five patients with an average age of 60.55 ± 14.04 years were evaluated. Out of 75, 48 (64%) were male and 27 (36%) were female. There was inhospital mortality in 20 (26.67%) patients. The mean NT-proBNP levels among the mortality group was 9826.95 ± 3485.10 pg/mL, while in nonmortality group, it was 6135.40 ± 2342.77 pg/mL (P = 0.001). The cutoff range in this study for on-admission serum NT-proBNP levels was 8990 pg/mL, with AUROC of 0.81, the sensitivity of 70.0%, and specificity of 90.9%. In multiple regression analysis keeping mortality as the dependent variable, it was seen that variables NT-proBNP, 6MWT (&lt;300 m), and LVEF were significantly associated with mortality. Conclusion: Serum NT-proBNP and 6MWT (&lt;300 m) were important predictors of mortality in advanced HF.

Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. The 158 patients (56.7 ± 13.6years, 28.5% female) studied had a median CPP of 40mmHg (IQR 35-52mmHg). During 6months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

Impact of frailty on mortality and morbidity in bridge to transplant recipients of contemporary durable mechanical circulatory support.

Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients. Patients undergoing left ventricular assist device (LVAD, n=96) or biventricular support (BiV, n=11) as BTT underwent frailty assessment. Frailty was defined as ≥ 3 physical domains of the Fried's Frailty Phenotype (FFP) or ≥ 2 physical domains of the FFP plus cognitive impairment on the Montreal Cognitive Assessment (MoCA). No difference in mortality at 360 days was observed in frail (n=6/38, 15.8%) vs non-frail (n=4/58, 6.9%) LVAD supported patients, p=0.19. However, there was a significant excess mortality in frail BiV (n=4/5) vs non-frail BiV (n=0/6) supported patients, p=0.013. In all patients, frail patients compared to non-frail patients experienced longer intensive care unit stay, 12 vs 6 days (p < 0.0001) and hospital length of stay, 48 vs 27 days (p < 0.0001). There was no difference in hemocompatibility and infection related adverse events. The majority (n=22/29, 75.9%) of frail patients became non-frail following MCS; contrastingly, a minority (n=3/42, 7.1%) became frail from being non-frail (p=0.0003). Abnormal markers of frailty are common in patients undergoing BTT-MCS support and those used herein predict mortality in BiV-supported patients, but not in LVAD patients. These findings may help us better identify patients who will benefit most from BiV-BTT therapy.

Systemic arterial pulsatility index (SAPi) predicts adverse outcomes in advanced heart failure patients.

Ventriculo-arterial (VA) coupling has been shown to have physiologic importance in heart failure (HF). We hypothesized that the systemic arterial pulsatility index (SAPi), a measure that integrates pulse pressure and a proxy for left ventricular end-diastolic pressure, would be associated with adverse outcomes in advanced HF. We evaluated the SAPi ([systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure) obtained from the final hemodynamic measurement in patients randomized to therapy guided by a pulmonary arterial catheter (PAC) and with complete data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Cox proportional hazards regression was performed for the outcomes of (a) death, transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and (b) DTxLVAD. Among 142 patients (mean age 56.8±13.3years, 30.3% female), the median SAPi was 2.57 (IQR 1.63-3.45). Increasing SAPi was associated with significant reductions in DTxLVAD (HR 0.60 per unit increase in SAPi, 95% CI 0.44-0.84) and DTxLVADHF (HR 0.81 per unit increase, 95% CI 0.70-0.95). Patients with a SAPi ≤ 2.57 had a marked increase in both outcomes, including more than twice the risk of DTxLVAD (HR 2.19, 95% CI 1.11-4.30) over 6months. Among advanced heart failure patients with invasive hemodynamic monitoring in the ESCAPE trial, SAPi was strongly associated with adverse clinical outcomes. These findings support further investigation of the SAPi to guide treatment and prognosis in HF undergoing invasive hemodynamic monitoring.

PO-633-03 RIGHT VENTRICULAR PRESSURE ANALYSIS ASSESSING THE IMPACT OF DIFFERENT PACING STRATEGIES DURING A LEFT VENTRICULAR ASSIST DEVICE SPEED OPTIMIZATION STUDY

CRT restores ventricular synchrony and improves outcomes in advanced heart failure. It is unknown if the benefit of CRT persists post LVAD; recent data suggest improved performance status and quality of life with RV-only versus biventricular (BiV) pacing. The mechanism underlying this observation is uncertain.

Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial.

Heart failure disproportionately affects Black patients. Whether differences among race influence outcomes in advanced heart failure with use of a fully magnetically levitated continuous-flow left ventricular assist device remains uncertain. We included 515 IDE (Investigational Device Exemption) clinical trial patients and 500 Continued Access Protocol patients implanted with the HeartMate 3 left ventricular assist device in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3). Outcomes were compared between Black and White left ventricular assist device recipients for the primary end point of survival free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years, overall survival, adverse events, 6-minute walk distance, and quality of life scores. Of 1015 HeartMate 3 patients, 675 were self-identified as White and 285 as Black individuals. The Black patient cohort was younger, more obese and with a history of hypertension, and more nonischemic cause of heart failure, relative to the White patient group. Black and White patients did not experience a difference in the primary end point (81.1% versus 77.9%; hazard ratio, 1.08 [95% CI, 0.76-1.54], P=0.6568). Black patients were at higher risk of adverse events (calculated as events per 100 patient-years), including bleeding (75.4 versus 63.5; P<0.0001), stroke (9.5 versus 7.2; P=0.0183), and hypertension (10.1 versus 3.2; P<0.0001). The 6-minute walk distance was not different at baseline and 6 months between the groups, however, the absolute change from baseline was greater for White patients (median: +183.0 [interquartile range, 42.0-335.3] versus +163.8 [interquartile range, 42.3-315.0] meters, P=0.01). The absolute quality of life measurement (EuroQoL group, 5-dimension, 5-level instrument visual analog scale) at baseline and 6 months was better in the Black patient group, but relative improvement from baseline to 6 months was greater in White patients (median: +20.0 [interquartile range, 5.0-40.0] versus +25.0 [interquartile range, 10.0-45.0]; P=0.0298). Although the survival free of disabling stroke or reoperation to replace/remove a malfunctioning device at 2 years with the HM 3 left ventricular assist device did not differ by race, Black HeartMate 3 patients experienced a higher morbidity burden and smaller gains in functional capacity and quality of life when compared with White patients. These findings require efforts designed to better understand and overcome these gaps through systematic identification and tackling of putative factors. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02224755 and NCT02892955.

A varied approach to left ventricular assist device follow-up improves cost-effectiveness

Background Left ventricular assist device (LVAD) implantation improves outcomes in advanced heart failure, however, the optimal frequency of outpatient assessments to improve cost-effectiveness and potentially avert readmissions is unclear. Methods To test if varying the frequency of follow-up after LVAD implantation reduces readmissions and improves cost-effectiveness, a less intensive follow-up (LIFU) strategy with scheduled visits at 1 month and then every 6 months was compared to an intensive follow-up (IFU) group with scheduled visits at 1, 2, and 4 weeks, and then every 3 months post-implant. We developed a decision-tree model to evaluate the cost-effectiveness of different follow-up schedules at 3, 6, and 12-months. The readmission rates for LIFU and IFU, along with the associated costs, were estimated using data from the IBM MarketScan Commercial Claims Databases (2015–2018). A total of 349 patients were enrolled, with 193 and 156 in the IFU and LIFU groups. Results Patients with IFU were found to have a lower risk for readmission at 3 months (HR: 0.69, 95% confidence interval (CI): 0.60–0.79), but this difference diminished overtime at 6 months (HR: 0.84, 95% CI: 0.73–0.96) and 12 months (HR: 0.94, 95% CI: 0.83–1.06). The incremental net benefit of IFU, when compared with LIFU, is greatest in the first 3 months and also diminishes over time (3 months: $19616, 6 months $9257, 12 months $717). Conclusions An initial IFU strategy, followed by a period of de-escalation at the 6-month post-implant mark in lower-risk patients, may be a more cost-effective strategy to provide follow-up care while not predisposing patients to a higher risk of readmission.

Phenotype-Guided Inflammation-Related Long Non-Coding RNA Discovery in Heart Failure Survival Prediction

Purpose Disease associated long non-coding RNAs (lncRNAs) may yield biomarkers to assess the risk of disease progression, facilitating treatment decisions. We hypothesize that identification of lncRNA genes related to recovery/survival outcome in Advanced Heart Failure (AdHF) patients after various surgical/interventional therapies (S/IT), and integration of these lncRNAs into our existing independently validated outcome prediction algorithm further improves the survival prediction precision vs clinical parameters alone. Methods Study was conducted on 77 AdHF patients undergoing various S/IT. Clinical data was collected within 30 days before and 1 year post S/IT. All patients were assigned survivor/non survivor status based on 1 year outcome. Blood samples were collected within 30 days pre-intervention. Total RNA was isolated from peripheral blood mononuclear cells (PBMC) for RNAseq genomic/transcriptomic analysis. Raw RNAseq data was aligned to Hg19 build and subjected to DESeq normalization in StrandNGS software (3.2). Genes with fold change of 2.0 were included in the analysis. Biological significance, functional characterization, pathway analysis were assessed using GO annotations/KEGG/DAVID/BioCarta/GeneCards/LNCipedia databases. Results Out of 161 differentially expressed and patented AdHF outcome prediction genes we identified 13 lncRNAs related to 1 year survival/functional recovery. SEPT5-GP1BB was upregulated in AdHF patients surviving after S/IT and its neighbor protein coding genes (SEPT5, GP1BB, synphilin1, PARK2) involved in proteolysis pathway responsible for degrading regulatory proteins, have a role in immune/inflammatory responses. HIF1A-AS2 was upregulated in surviving patients and can be predictive based on its effect on the organ failure/hypoxia induced angiogenesis. XIST was upregulated in surviving patients, it is known to co-occur with at least 14 coding genes. The predictive information of XIST on survival might be linked to its immunomodulatory effect. Conclusion Differentially expressed lncRNA genes from PBMCs are correlated with recovery/1 year survival outcomes in AdHF patients and can be systematically identified by a phenotype guided NGS strategy. Incorporation of lncRNA data will allow for optimization of our existing multidimensional outcome prediction algorithm.

Endocrine Challenges in Patients with Continuous-Flow Left Ventricular Assist Devices

Heart failure (HF) remains a leading cause of morbidity, hospitalization, and mortality worldwide. Advancement of mechanical circulatory support technology has led to the use of continuous-flow left ventricular assist devices (LVADs), reducing hospitalizations, and improving quality of life and outcomes in advanced HF. Recent studies have highlighted how metabolic and endocrine dysfunction may be a consequence of, or associated with, HF, and may represent a novel (still neglected) therapeutic target in the treatment of HF. On the other hand, it is not clear whether LVAD support, may impact the outcome by also improving organ perfusion as well as improving the neuro-hormonal state of the patients, reducing the endocrine dysfunction. Moreover, endocrine function is likely a major determinant of human homeostasis, and is a key issue in the recovery from critical illness. Care of the endocrine function may contribute to improving cardiac contractility, immune function, as well as infection control, and rehabilitation during and after a LVAD placement. In this review, data on endocrine challenges in patients carrying an LVAD are gathered to highlight pathophysiological states relevant to this setting of patients, and to summarize the current therapeutic suggestions in the treatment of thyroid dysfunction, and vitamin D, erythropoietin and testosterone administration.

Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function.

Ventilatory efficiency (minute ventilation required to eliminate carbon dioxide, VE/VCO2) during exercise potently predicts outcomes in advanced heart failure with reduced ejection fraction, but its prognostic significance for at-risk individuals with preserved left ventricular systolic function is unclear. We aimed to characterize mechanistic determinants and prognostic implications of VE/VCO2 in a single-center dyspneic referral cohort (MGH-ExS [Massachusetts General Hospital Exercise Study]) and in a large sample of community-dwelling participants in the FHS (Framingham Heart Study). Maximum incremental cardiopulmonary exercise tests were performed. VE/VCO2 was assessed as the slope pre- and post-ventilatory anaerobic threshold (VE/VCO2pre-VATslope, VE/VCO2post-VATslope), the slope throughout exercise (VE/VCO2overall-slope), and as the lowest 30-second value (VE/VCO2nadir). In the MGH-ExS (N=493, age 56±15 years, 61% women, left ventricular ejection fraction 64±8%), higher VE/VCO2nadir was associated with lower peak exercise cardiac output and steeper increases in exercise pulmonary capillary wedge pressure (both P<0.0001). VE/VCO2nadir (hazard ratio, 1.34 per 1-SD unit [95% CI, 1.10-1.62] P=0.003) was associated with future cardiovascular hospitalization/death and outperformed classical VE/VCO2 measures used in heart failure with reduced ejection fraction (VE/VCO2overall-slope). In FHS (N=1936, age 54±9 years, 53% women), VE/VCO2 measures taken in low-to-moderate intensity exercise (including VE/VCO2pre-VATslope, VE/VCO2nadir) were directly associated with cardiovascular risk factor burden (smoking, Framingham cardiovascular disease risk score, and lower fitness; all P<0.001). Impaired ventilatory efficiency is associated with cardiovascular risk in the community and with adverse hemodynamic profiles and future hospitalizations/death in a referral population, highlighting the prognostic importance of easily acquired submaximum exercise ventilatory gas exchange measurements in broad populations with preserved left ventricular systolic function.

Reversal of Frailty after LVAD Associated with Significant Reduction in Markers of Inflammation

Inflammation has been implicated in frailty seen in heart failure (HF), and macrophage migration inhibitory factor (MIF) has been associated with worse outcomes in HF. Assessment of frailty is key in determining eligibility for advanced therapies (AT). Most programs use a subjective assessment (SA), but the Modified Fried Frailty Index (mFFI) has been widely validated. We assessed MIF levels in patients referred for AT and the changes in mFFI and MIF after LVAD. Additionally, we compared SA to mFFI testing in patients referred for AT. All patients referred for evaluation for AT underwent SA and mFFI assessments and blood testing for MIF. Three providers (Ps) independently assessed patients to be frail or not frail (SA). mFFI assigns a frailty point in each of five domains: weight loss, fatigue, activity, walk time, and strength. Patients are frail when scored ≥ 3. Patients who underwent LVAD were reevaluated for mFFI and MIF at 3 and 6 months. Over 18 months, 54 subjects (61±11 yrs) were studied, 11 underwent LVAD. Frail patients were older, and had lower albumin and Hb. SA significantly underestimated frailty compared to mFFI (3-23% vs. 60%, p<0.001) (Fig. 1A). Correlation between SA and mFFI was not strong (42-58% agreement, κ< 0.04). Most of the time, Ps were correct when designating a patient as frail and incorrect when designating a patient as not frail. Agreement between all 3 Ps was strong (71.4%, W= .34). Baseline MIF was elevated in AT patients (311±128 pg/mL). mFFI scores improved in all patients by 6 months after LVAD, such that they were significantly lower than baseline (2.9±1.4 vs. 0.9±0.9, p<0.003), with no patients being assessed as frail. In parallel, MIF significantly decreased after LVAD (Fig. 1B). SA significantly underestimates frailty as compared to mFFI. Both frailty scores and MIF improved after LVAD, suggesting reversibility of the frailty syndrome. Understanding frailty will be key to improving outcomes in advanced HF.

Impact of left ventricular assist device implantation on mitral regurgitation: An analysis from the MOMENTUM 3 trial

Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated. We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms. Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant MR at baseline. At 1-month of support, residual MR was present in 6.2% of patients with HM3 and 14.3% of patients with HMII (relative risk = 0.43; 95% CI, 0.22-0.84; p = 0.01) with a low rate of worsening at 2years. Residual MR at 1-month post-implant did not impact 2-year mortality for either the HM3 (hazard ratio [HR],1.41; 95% CI, 0.52-3.89; p = 0.50) or HMII (HR, 0.91; 95% CI, 0.37-2.26; p = 0.84) LVAD. The presence or absence of baseline MR did not influence mortality (HM3 HR, 0.86; 95% CI, 0.56-1.33; p = 0.50; HMII HR, 0.81; 95% CI, 0.54-1.22; p = 0.32), major adverse events or functional capacity. In multivariate analysis, severe baseline MR (p = 0.001), larger left ventricular dimension (p = 0.002), and implantation with the HMII instead of the HM3 LVAD (p = 0.05) were independently associated with an increased likelihood of persistent MR post-implant. Hemodynamic unloading after LVAD implantation improves clinically significant MR early, sustainably, and to a greater extent with the HM3 LVAD. Neither baseline nor residual MR influence outcomes after LVAD implantation.

First Let's Try… Will the Success of New Therapies Paradoxically Challenge Outcomes in Advanced Heart Failure?

First Let's Try… Will the Success of New Therapies Paradoxically Challenge Outcomes in Advanced Heart Failure?

Producing an effective care plan in advanced heart failure.

An effective discharge plan is associated with better outcomes in advanced heart failure (HF) patients. Furthermore, a patient-centred care planning can improve patients’ satisfaction, quality of life, and enhance self-care. Telemedicine may allow optimized monitoring of advanced HF patients. Nevertheless, its implementation into clinical practice across European countries is still limited. This document reflects the key points discussed concerning effective management plans in advanced HF by a panel of experts during a Heart Failure Association meeting on physiological monitoring of the complex multimorbid HF patient.