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Background: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. Methods: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7–8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. Results: In cohort A, median (interquartile range) age was 62 years (47–71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4–9). In cohort B, median (interquartile range) age was 59 years (49–71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6–9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P ≤0.002) and were greater in the high-risk compared with the low-risk category ( P ≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P =0.0001) and REVEAL risk groups (log-rank: P P =0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P P ≤0.02). Conclusions: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.

Heart failure-related cardiogenic shock (HF-CS) remains an understudied distinct clinical entity.The authors sought to profile a large cohort of patients with HF-CS focused on practical application of the Society of Cardiovascular AngiographyCardiovascular Interventions (SCAI) staging system to define baseline and maximal shock severity, in-hospital management with acute mechanical circulatory support (AMCS), and clinical outcomes.The Cardiogenic Shock Working Group registry includes patients with CS, regardless of etiology, from 17 clinical sites enrolled between 2016 and 2020. Patients with HF-CS (non-acute myocardial infarction) were analyzed and classified based on clinical presentation, outcomes at discharge, and shock severity defined by SCAI stages.A total of 1,767 patients with HF-CS were included, of whom 349 (19.8%) had de novo HF-CS (DNHF-CS). Patients were more likely to present in SCAI stage C or D and achieve maximum SCAI stage D. Patients with DNHF-CS were more likely to experience in-hospital death and in- and out-of-hospital cardiac arrest, and they escalated more rapidly to a maximum achieved SCAI stage, compared to patients with acute-on-chronic HF-CS. In-hospital cardiac arrest was associated with greater in-hospital death regardless of clinical presentation (de novo: 63% vs 21%; acute-on-chronic HF-CS: 65% vs 17%; both P 0.001). Forty-five percent of HF-CS patients were exposed to at least 1 AMCS device throughout hospitalization.In a large contemporary HF-CS cohort, we identified a greater incidence of in-hospital death and cardiac arrest as well as a more rapid escalation to maximum SCAI stage severity among DNHF-CS. AMCS use in HF-CS was common, with significant heterogeneity among device types. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).

The goal of this review is to summarize the current knowledge on the role of medical management of cardiogenic shock in the era of mechanical circulatory support based on important lessons from clinical trials and routine clinical practice, with a focus on providing practical recommendations that can improve contemporary in-hospital management.Despite an increasing number of invasive therapies being used to manage cardiogenic shock, evidence-based treatment regimens known to improve outcomes are limited. Medical management of cardiogenic shock includes pharmacological interventions aimed at optimizing determinants of cardiac output-contractility, preload, afterload, and heart rate. In this regard, inotropes and vasopressors remain cornerstone therapies for the management of cardiogenic shock. Norepinephrine has shown potential vasopressor advantage with compared with dopamine, and although milrinone and dobutamine are both considered appropriate first-line inotropes, there is limited data to guide selection, and a recent randomized clinical trial found no significant differences in the treatment of cardiogenic shock.In the absence of an evidence-based management approach to cardiogenic shock, clinical guidelines are based on expert opinion and routine clinical practice patterns. Further studies focusing on clinical outcomes among specific cardiogenic shock phenotypes are needed to better assess the clinical efficacy of these agents.

Preoperative variables can predict short term left ventricular assist device (LVAD) survival, but predictors of extended survival remain insufficiently characterized.Patients undergoing LVAD implant (2012-2018) in the Intermacs registry were grouped according to time on support: short-term (1 year, n = 7,483), mid-term (MT, 1-3 years, n = 5,976) and long-term (LT, ≥3 years, n = 3,015). Landmarked hazard analyses (adjusted hazard ratio, HR) were performed to identify correlates of survival after 1 and 3 years of support.After surviving 1 year of support, additional LVAD survival was less likely in older (HR 1.15 per decade), Caucasian (HR 1.22) and unmarried (HR 1.16) patients (p0.05). After 3 years of support, only 3 preoperative characteristics (age, race, and history of bypass surgery, p0.05) correlated with extended survival. Postoperative events most negatively influenced achieving LT survival. In those alive at 1 year or 3 years, the occurrence of postoperative renal (creatinine HR MT = 1.09; LT HR = 1.10 per mg/dl) and hepatic dysfunction (AST HR MT = 1.29; LT HR = 1.34 per 100 IU), stroke (MT HR = 1.24; LT HR = 1.42), infection (MT HR = 1.13; LT HR = 1.10), and/or device malfunction (MT HR = 1.22; LT HR = 1.46) reduced extended survival (all p ≤ 0.03).Success with LVAD therapy hinges on achieving long term survival in more recipients. After 1 year, extended survival is heavily constrained by the occurrence of adverse events and postoperative end-organ dysfunction. The growth of destination therapy intent mandates that future LVAD studies be designed with follow up sufficient for capturing outcomes beyond 24 months.

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF., In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.

Background Understanding the prognostic impact of right ventricular dysfunction (RVD) in cardiogenic shock (CS) is a key step toward rational diagnostic and treatment algorithms and improved outcomes. Using a large multicenter registry, we assessed (1) the association between hemodynamic markers of RVD and in-hospital mortality, (2) the predictive value of invasive hemodynamic assessment incorporating RV evaluation, and (3) the impact of RVD severity on survival in CS. Methods and Results Inpatients with CS owing to acute myocardial infarction (AMI) or heart failure (HF) between 2016 and 2019 were included. RV parameters (right atrial pressure, right atrial/pulmonary capillary wedge pressure [RA/PCWP], pulmonary artery pulsatility index [PAPI], and right ventricular stroke work index [RVSWI]) were assessed between survivors and nonsurvivors, and between etiology and SCAI stage subcohorts. Multivariable logistic regression analysis determined hemodynamic predictors of in-hospital mortality; the resulting models were compared with SCAI staging alone. Nonsurvivors had a significantly higher right atrial pressure and RA/PCWP and lower PAPI and RVSWI than survivors, consistent with more severe RVD. Compared with AMI, patients with HF had a significantly lower RA/PCWP (0.58 vs 0.66, P = .001) and a higher PAPI (2.71 vs 1.78, P Conclusions RVD is associated with poor outcomes in CS, with key differences across etiology and shock severity. Further studies are needed to assess the usefulness of RVD assessment in guiding therapy.

Purpose Sympathetic activation results in a functional distribution of venous blood from the unstressed reservoir to the hemodynamically active stressed compartment. Such redistribution has been hypothesized to contribute importantly to the elevated filling pressures observed in decompensated heart failure and cardiogenic shock (CS). We recently reported a novel computational method to estimate SBV by fitting measured hemodynamic data from patients to outputs from a cardiovascular model. We hypothesized that estimated stressed blood volume (eSBV) may correlate with severity and clinical outcomes in cardiogenic shock. Methods Hemodynamic parameters including eSBV were compared among a subset of patients from the Cardiogenic Shock Working Group (CSWG) registry who had a complete set of hemodynamic data. eSBV was compared across shock etiologies (AMI vs HF-CS), SCAI stage, and between survivors and non-survivors. Results Among 528 CSWG registry patients analyzed, 25.4% had AMI-CS and 61.9% had HF-CS. Mean eSBV was 2423 ± 531 mL/70 kg (normal value ∼1500 mL) and was similar between the AMI-CS and HF-CS subgroups (2421 ± 478 vs 2342 ± 599 mL/70kg, p=0.90). eSBV increased with increasing SCAI stage (B, 2029 ± 540; C, 2305 ± 505; D, 2496 ± 507; E, 2707 ± 420 mL/70 kg, p Conclusion eSBV is a novel integrated index of congestion which correlates with shock severity. eSBV was higher in patients with HF-CS who died while no difference was observed in AMI-CS, suggesting that congestion may play a more significant role in the deterioration of patients with HF-CS.

OBJECTIVE Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease that often follows pulmonary embolism (PE). Screening for CTEPH is challenging, often delaying diagnosis and worsening prognosis. Predictive risk models for CTEPH could help identify at-risk patients, but existing models require multiple clinical inputs. We developed and validated a predictive risk model for CTEPH using health insurance claims that can be used by payers/quality-of-care organizations to screen patients post-PE. METHODS Adult patients newly diagnosed with acute PE (index date) were identified from the Optum De-identified Clinformatics Extended DataMart (January 2007-March 2018; development set) and IBM MarketScan (January 2008-June 2019; validation set) databases. Predictors were identified 12 months before or on the index PE. Risk of "likely CTEPH" was assessed post-PE based on CTEPH-related diagnoses and procedures since the CTEPH diagnosis code (ICD-10-CM: I27.24) was not available until 1 October 2017. Stepwise variable selection was used to build the model using the development set; model validation was subsequently conducted using the validation set. RESULTS The development set included 93,428 patients, of whom 11,878 (12.7%) developed likely CTEPH. Older age (odds ratios [OR] = 1.16-1.49), female (OR = 1.09), unprovoked PE (i.e. without thrombotic factors; OR = 1.14), hypertension (OR = 1.07), osteoarthritis (OR = 1.08), diabetes (OR = 1.07), chronic obstructive pulmonary disease (OR = 1.11), obesity (OR = 1.21) were associated with higher odds of likely CTEPH, and oral anticoagulants with lower odds (OR= 0.50, all p

Left ventricular assist devices (LVADs) are life-saving therapies for patients in end-stage heart failure (HF) with reduced ejection fraction regardless of candidacy for heart transplantation. Multiple clinical trials have demonstrated improved morbidity and mortality with LVADs when compared to medical therapy alone. However, the uptake of LVADs as a therapeutic option in a larger section of end-stage HF patients remains limited, partly due to associated adverse events and re-hospitalization.Accurate assessment and staging of HF patients is crucial to guide appropriate use of LVADs. Innovative methods to risk stratify patients and manage cardiac and noncardiac comorbidities can translate to improved outcomes in LVAD recipients. Inclusion of quality of life metrics and measurements of adverse events can better inform heart failure cardiologists to help identify ideal LVAD candidates. Addition of machine learning algorithms to this process may guide patient selection to improve outcomes.Patient selection and assessment of reversible medical comorbidities are critical to the postoperative success of LVAD implantation. Identifying patients most likely to benefit and least likely to experience adverse events should be a priority.

Rationale: Event-driven primary endpoints are increasingly used in pulmonary arterial hypertension clinical trials, substantially increasing required sample sizes and trial lengths. The U.S. Food a...

Background: Venous thromboembolism (VTE) is a common medical problem seen in primary care settings. The most common long-term adverse sequelae are recurrent thromboembolism and incomplete resolution of the embolic material, which may result in pulmonary hypertension after pulmonary embolism and post-thrombotic changes in the leg after deep vein thrombosis. Although there are detailed guidelines for diagnosing and treating acute VTE, there are few focused articles that provide recommendations for primary care physicians (PCPs) about how to manage VTE patients after completion of the initial period of anticoagulation treatment. Observations: In this article, we highlight several important clinical decisions that must be addressed after the first 3 months of anticoagulation treatment is complete, with a focus on particular management issues for PCPs. Conclusions: The 2 most important decisions the PCP must make are to determine, first, if symptoms of acute VTE have indeed resolved, and second, if they have resolved, to assess the long-term risk of recurrent VTE versus the risk of potential bleeding and decide if anticoagulation should be stopped, or if indefinite anticoagulation treatment is indicated. Among higher-risk patients who may benefit from indefinite anticoagulation, the PCP should discuss both the risks and benefits of anticoagulation treatment, empowering the patient to actively participate in this important shared decision-making process.

Objectives The purpose of this study was to investigate the association between obtaining hemodynamic data from early pulmonary artery catheter (PAC) placement and outcomes in cardiogenic shock (CS). Background Although PACs are used to guide CS management decisions, evidence supporting their optimal use in CS is lacking. Methods The Cardiogenic Shock Working Group (CSWG) collected retrospective data in CS patients from 8 tertiary care institutions from 2016 to 2019. Patients were divided by Society for Cardiovascular Angiography and Interventions (SCAI) stages and outcomes analyzed by the PAC-use group (no PAC data, incomplete PAC data, complete PAC data) prior to initiating mechanical circulatory support (MCS). Results Of 1,414 patients with CS analyzed, 1,025 (72.5%) were male, and 494 (34.9%) presented with myocardial infarction; 758 (53.6%) were in SCAI Stage D shock, and 263 (18.6%) were in Stage C shock. Temporary MCS devices were used in 1,190 (84%) of those in advanced CS stages. PAC data were not obtained in 216 patients (18%) prior to MCS, whereas 598 patients (42%) had complete hemodynamic data. Mortality differed significantly between PAC-use groups within the overall cohort (p Conclusions The CSWG is a large multicenter registry representing real-world patients with CS in the contemporary MCS era. Use of complete PAC-derived hemodynamic data prior to MCS initiation is associated with improved survival from CS.

Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction (LVDD). Due to positive impact on transvalvular hemodynamics, transcatheter aortic valve replacement (TAVR) is expected to improve LV remodeling, LVDD and heart failure (HF)-related quality-of-life (QoL). We identified patients with severe AS and LV ejection fraction (LVEF) ≥ 50% who underwent TAVR. We reviewed pre-procedure, 1-month and 1-year post-TAVR transthoracic echocardiograms to assess LV volumetric changes and diastolic function. QoL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). In 171 patients studied, we found significant improvement in LV mass index (LVMI), LV end-systolic diameter and LV end-diastolic diameter from baseline to 1-month to 1-year post-TAVR. Predictors of LVMI regression included greater change from baseline in mean aortic valve (AV) gradient, peak AV velocity, and improvements in septal and lateral e’ velocities and E/e’ post-TAVR. The percentage of patients with ≥ grade 2 LVDD decreased from 65% to 53% at 1-month and 49% at 1-year. A significant improvement in symptomatology, as reported by KCCQ score was also noted. There is conceivable reverse LV remodeling post-TAVR, impacted by improvements in mean AV gradient, peak AV velocity, E/e’, medial and lateral e’ velocities, which occurs immediately post-TAVR and persists up to 1-year post-operatively. This is associated with concomitant improvement in LVDD and HF-related QoL as demonstrated by KCCQ scores.

Pulmonary hypertension (PH) frequently co-exists in patients with severe aortic stenosis (AS). In this study, we sought to identify the implications of invasive pulmonary hemodynamics on major adverse cardiac events (MACE), biventricular function and NYHA functional class after transcatheter aortic valve replacement (TAVR).Invasive hemodynamics via right heart catheterization (RHC) were performed pre-TAVR. Patients were stratified per mean PA pressure (mPAP), diastolic pulmonary gradient (DPG) and pulmonary vascular resistance (PVR), and followed at 1-month and 1-year intervals up to 6 years. MACE outcomes included cardiovascular death and heart failure hospitalizations post-TAVR.Among 215 patients, Kaplan-Meir estimates demonstrated an increased 1-year risk of MACE from 8% among those without pre-TAVR PH to 27% among patients with pre-existing PH. Specifically, the MACE risk was 32% among PH patients with PVR ≥ 3WU (p = .04) and 53% among PH patients with DPG ≥ 7 mm Hg (p.01). On univariate Cox regression, RV stroke work index (RVSWI) (HR,1.02; p = .02), and pulmonary hemodynamic index (PHI) (HR,1.27; p = .047) were identified as additional predictors of MACE post-TAVR. On multivariable Cox regression analysis, SvO2 (HR, 0.95; p = .01) and PVR (HR, 1.2; p = .04) were demonstrated as predictive of MACE post-TAVR. A significant improvement in LVEF (2-Factor ANOVA, p.01) and RV fractional area change (RVFAC%) (p.01) was noted as assessed at baseline, 1-month and 1-year follow up post-TAVR. There was a significant interaction between pre-TAVR PH status and time post procedure with respect to NYHA functional class (p = .03), that is, the manner and degree of change in NYHA class over time depended on pre-TAVR PH status.Defining invasive pulmonary hemodynamics, such as mPAP, PVR, and DPG among patients with severe AS undergoing TAVR has significant prognostic implications. Routine risk stratification by utilizing invasive hemodynamics can better identify patients who will have functional improvement and improved outcomes post-TAVR.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

With improvement in the understanding of the pathophysiological mechanisms of heart failure with reduced ejection fraction (HFrEF), several drug classes have been developed targeting the renin-angiotensin-aldosterone system, the beta adrenergic system, and to a certain extent the nitric oxide pathway. Recently, the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors has resulted in a reduction in heart failure hospitalizations and cardiovascular death. As a result, SGLT-2 inhibitors are now the fourth drug class recommended as part of guideline-directed medical therapy (GDMT) for HFrEF. Soluble guanylate cyclase (sGC) stimulators, such as vericiguat, are a novel therapy targeting the cyclic guanosine monophosphate (cGMP) pathway with downstream effects including smooth muscle cell relaxation and a reduction in hypertrophy, inflammation, and fibrosis. The recently published VICTORIA trial has demonstrated a reduction in heart failure hospitalizations or cardiovascular death with vericiguat. Patients with a baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) values8000 pg/mL may identify a sub-group most likely to benefit with addition of vericiguat. The cumulative benefit of quadruple therapy with the addition of sGC stimulators remains unknown. We review the mechanism of action for sGC stimulators, clinical trial data, and their real-world application to HFrEF patients with consideration of quintuple therapy.

Background: Cell-free DNA (cfDNA) is a non-invasive marker of tissue injury. Although being incrementally used as a clinical biomarker, its significance in pulmonary arterial hypertension (PAH) is unknown. Methods: Plasma cfDNA was isolated in two independent PAH cohorts (A, n=48; B, n=161) and healthy controls (n=48). Clinical variables and survival status were collected for Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL 2.0) scores and outcome determinations. Total cfDNA levels were compared amongst controls and PAH patients and also used to predict transplant-free survival. A subset of samples from cohort B (n=96) and controls (n=16) were subjected to bisulfite sequencing and methylation analysis to quantify tissue-specific sources of cfDNA. Results: Median (IQR) cfDNA concentrations were higher in cohort A PAH patients (exploratory cohort) compared to controls and increased according to REVEAL 2.0 risk group: controls 13.7 (10.8-18.8) vs low risk 14.4 (10.0-19.9) vs medium risk 14.6 (11.3-28.2) vs high risk 31.5 (17.2-45.6) ng/ml (P Conclusions: cfDNA is elevated in PAH patients, correlates with disease severity and predicts worse survival. Methylation analysis of cfDNA in PAH patients is consistent with prevailing paradigms of disease pathogenesis. Thus, cfDNA may add prognostic power to PAH risk assessment and provide insight into disease progression.

Background: Pulmonary arterial hypertension (PAH) is a fatal and difficult to treat disease due to patient inter-variability. Accurate risk stratification is necessary for guiding treatment but no PAH risk calculator has achieved "excellent performance" (receiver-operator AUC > 0.8). Conversion of REVEAL 2.0 to a Bayesian network has shown promising results (Pulmonary Hypertension Outcomes Risk Assessment or PHORA). In this study, a new Bayesian network model (PHORA 2.0) was developed with a novel network structure and optimal feature selection. Methods: Patient-level data had been previously aggregated and harmonized across six PAH clinical trials (AMBITION, PATENT-1/2, GRIPHON, SERAPHIN, FREEDOM-EV, ARIES-1/2); all patients were assessed at baseline. Forty-one variables were initially considered based on p-value ranking from previous meta-analyses, availability across trials, and expert opinion. Training data was created by random sampling of 80% of the harmonized dataset, dropping early censored patients (N = 2531), leaving 20% of the data as a test set (N = 626). Continuous variables were discretized through univariate decision trees using 10-fold cross-validation maximizing Brier score. Genetic search selected combinations of features that maximized ranked correlation (Kendall’s tau) with one-year survival, with increasing penalty for redundant features. Feature combinations were evaluated in augmented naïve Bayesian networks, the best model was selected by 10-fold cross-validation on training data. Final performance is reported as performance on the test set. Results: The final model achieved the best cross-validation AUC using 16 variables. Performance on the test set was an AUC = 0.85. The final model outperformed multiple risk calculators at test time (Figure 1). Conclusion: Bayesian network modeling coupled with genetic feature selection has discovered for the first time a one-year mortality model for PAH with excellent performance.

Background Pulmonary arterial hypertension (PAH) is a chronic disease that ultimately progresses to right-sided heart failure (HF) and death. Close monitoring of pulmonary artery pressure (PAP) and right ventricular (RV) function allows clinicians to appropriately guide therapy. However, the burden of commonly used methods to assess RV hemodynamics, such as right heart catheterization, precludes frequent monitoring. The CardioMEMS HF System (Abbott) is an ambulatory implantable hemodynamic monitor, previously only used in patients with New York Heart Association (NYHA) class III HF. In this study, we evaluate the feasibility and early safety of monitoring patients with PAH and right-sided HF using the CardioMEMS HF System. Methods The CardioMEMS HF sensors were implanted in 26 patients with PAH with NYHA class III or IV right-sided HF (51.3 ± 18.3 years of age, 92% women, 81% NYHA class III). PAH therapy was tracked using a minimum of weekly reviews of CardioMEMS HF daily hemodynamic measurements. Safety, functional response, and hemodynamic response were tracked up to 4 years with in-clinic follow-ups. Results The CardioMEMS HF System was safely used to monitor PAH therapy, with no device-related serious adverse events observed and a single preimplant serious adverse event. Significant PAP reduction and cardiac output elevation were observed as early as 1 month postimplant using trends of CardioMEMS HF data, coupled with significant NYHA class and quality of life improvements within 1 year. Conclusions The CardioMEMS HF System provided useful information to monitor PAH therapy, and demonstrated short- and long-term safety. Larger clinical trials are needed before its widespread use to guide therapy in patients with severe PAH with right-sided HF.

Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay., A large multicenter study in a broad heart transplant surveillance population demonstrates the ability of standardized donor‐ derived cell‐free DNA testing to identify both T cell–mediated and antibody‐mediated acute rejection with a high negative predictive value.

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

Background: Cardiogenic shock occurring in the setting of advanced heart failure (HF-CS) is increasingly common. However, recent studies have focused almost exclusively on acute myocardial infarction-related CS. We sought to define clinical, hemodynamic, metabolic, and treatment parameters associated with clinical outcomes among patients with HF-CS, using data from the Cardiogenic Shock Working Group registry. Methods: Patients with HF-CS were identified from the multicenter Cardiogenic Shock Working Group registry and divided into 3 outcome categories assessed at hospital discharge: mortality, heart replacement therapy (HRT: durable ventricular assist device or orthotopic heart transplant), or native heart survival. Clinical characteristics, hemodynamic, laboratory parameters, drug therapies, acute mechanical circulatory support device (AMCS) utilization, and Society of Cardiovascular Angiography and Intervention stages were compared across the 3 outcome cohorts. Results: Of the 712 patients with HF-CS identified, 180 (25.3%) died during their index admission, 277 (38.9%) underwent HRT (durable ventricular assist device or orthotopic heart transplant), and 255 (35.8%) experienced native heart survival without HRT. Patients who died had the highest right atrial pressure and heart rate and the lowest mean arterial pressure of the 3 outcome groups ( P 1 AMCS device had the highest in-hospital mortality rate irrespective of the number of vasoactive drugs used. Mortality increased with deteriorating Society of Cardiovascular Angiography and Intervention stages (stage B: 0%, stage C: 10.7%, stage D: 29.4%, stage E: 54.5%, 1-way ANOVA= Conclusions: Patients with HF-CS experiencing in-hospital mortality had a high prevalence of biventricular congestion and markers of end-organ hypoperfusion. Substantial heterogeneity exists with use of AMCS in HF-CS with intraaortic balloon pump being the most common device used and high rates of in-hospital mortality after exposure to >1 AMCS device.