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BACKGROUND The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension. RESEARCH QUESTION What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects? STUDY DESIGN AND METHODS This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019. RESULTS Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001). INTERPRETATION Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

An elevated right ventricular/pulmonary artery systolic pressure suggestive of pulmonary hypertension (PH) is a common finding noted on echocardiography and is considered a marker for poor clinical outcomes, regardless of the cause. Even mild elevation of pulmonary pressure can be considered a modifiable risk factor, informing the trajectory of patients' clinical outcome. Although guidelines have been published detailing diagnostic and management algorithms, this echocardiographic finding is often underappreciated or not acted upon. Hence, patients with PH are often diagnosed in clinical practice when hemodynamic abnormalities are already moderate or severe. This results in delayed initiation of potentially effective therapies, referral to PH centers, and greater patient morbidity and mortality. This mini‐review presents a succinct, simplified case‐based approach to the “next steps” in the work‐up of PH, once elevated pulmonary pressures have been noted on an echocardiogram. Our goal is for clinicians to develop a good overview of diagnostic approach to PH and recognition of high‐risk features that may require early referral.

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns. OBJECTIVE The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era. METHODS Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival. RESULTS Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival. CONCLUSIONS This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States. CLINICALTRIAL ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/25397

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns. Objective The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era. Methods Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival. Results Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival. Conclusions This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States. Trial Registration ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284 International Registered Report Identifier (IRRID) DERR1-10.2196/25397

A major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV).We enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment. All enrolled patients were on stable PH-specific therapy. Enrolled patients were assessed using CMR imaging, New York Heart Association functional class, N-terminal pro brain natriuretic peptide, 6-minute walk test, and quality of life health outcomes at baseline and repeated at the end of treatment. The primary outcome was change in RVEF after 6 months of treatment. Analysis of covariance was used to analyze the longitudinal changes taking into account baseline values, age, and sex, based on per protocol population. Twenty-two patients were enrolled, and 9 patients completed follow-up CMR imaging after ranolazine treatment and 6 completed placebo treatment. There was significant increase in RVEF at end of treatment compared with baseline in the ranolazine group adjusted for baseline values, age, and sex. There were no statistically significant changes in secondary outcomes such as changes in New York Heart Association functional class, 6-minute walk distance, N-terminal pro brain natriuretic peptide, or quality of life measures. Ranolazine treated patients experienced a higher number of adverse events, but only one was discontinued owing to side effects.Ranolazine may improve RV function in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Purpose To assess the efficacy and safety of macitentan in pts with PH post-LVAD. Methods SOPRANO (NCT02554903) was a double-blind, randomized, study of macitentan 10 mg once-daily vs placebo. Pts were ≥18 years with LVAD implanted within 90 days prior to randomization, had mean pulmonary arterial pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) ≤18 mmHg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The primary endpoint was change in PVR at week 12 of therapy from baseline. Results Fifty-seven pts were randomized: macitentan (n=28) or placebo (n=29). Baseline pt demographics and characteristics were well balanced. Baseline PVR (mean [SD]) was 4.3 [0.9] WU (macitentan) and 4.3 [1.3] WU (placebo). At week 12, mean PVR decreased to 58.5% (macitentan) and to 75.5% (placebo) of baseline. Mean placebo-corrected reduction in PVR of macitentan was 26.1% (95% CI: 58.0, 94.3; p=0.0158). Predefined secondary endpoints, notably including changes in PAWP, were not significantly different with macitentan vs placebo (Table). Another relevant hemodynamic parameter, transpulmonary gradient, significantly decreased with macitentan vs placebo (p=0.0499). The incidence of treatment adverse events (TAEs) was 21.4% (macitentan) and 24.1% (placebo); no TAEs occurred in >1 patient in the macitentan arm. AEs of interest included edema, anemia and hypotension: reported in 7 (25.0%), 3 (10.7%), and 4 (14.3%) pts on macitentan (mostly mild-moderate) and in 5 (17.2%), 2 (6.9%) and 1 (3.6%) pts on placebo, respectively. Two pts on macitentan and 1 pt on placebo discontinued for treatment-related AEs. Conclusion In the first prospective, multicenter, randomized controlled trial of pulmonary vasodilators in the early post-LVAD population, macitentan significantly reduced PVR and was well tolerated. The impact of macitentan on post-LVAD exercise capacity and RV failure warrants further study.

The model for end-stage liver disease (MELD) has been used as a predictor of mortality after left ventricular assist device (LVAD) placement. However, improvement or worsening of MELD and how those changes affect outcomes is unknown. We performed a retrospective analysis of 244 patients implanted with a continuous flow (CF) LVAD. Patients were dichotomized at admission into low- or high-risk categories using a cutoff of MELD ≥ 19, and they were reclassified at day of implant forming four groups: Group LL (low to low, remained low risk), LH (low to high, worsened to high risk), HH (high to high, remained high risk), and HL (high to low, improved to low risk). Patients who improved to a low risk (group HL) had the same 1 year survival as those that remained low risk (group LL; 80% vs. 77%; p = 0.6). However, patients who were initially classified as low risk and worsened to a high risk (group LH) had a survival that was worse than those that were consistently high risk (group HH; 55% vs. 10%; p = 0.01). Model for end-stage liver disease reclassification after adjusting for commonly attributed risk factors remained an independent predictor for mortality, including patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 and 2. In conclusion, our MELD score reclassification is an independent and powerful predictor of mortality in patients undergoing LVAD implantation.

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug-drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real-world issues in using macitentan to treat patients with PAH.

Background Anemia is common in patients with heart failure and is associated with adverse outcomes. Management of anemia in CF-LVAD patients is not well studied. Our purpose is to characterize and identify the etiology of anemia in CF-LVAD patients. Secondary objectives are to describe the effect of CF-LVAD on pre-existing anemia and assess its impact after CF-LVAD support. Methods Cross-sectional study from January to July 2015 of ambulatory patients supported with a CF-LVAD for at least 6-months that presented with hemoglobin Results In our cross-sectional cohort, iron deficiency was the most common cause of anemia. Notably, 49% of the iron-deficient patients were already on iron supplementation. In our retrospective cohort, 59% of the patients were anemic after 6 months of support. Anemic patients were older, had lower albumin, higher brain natriuretic peptide (BNP), worse renal function and New York Heart Association (NYHA) class. Anemia had a HR of 3.16 (95%CI 1.38–7.26) to predict a composite of 1-year death and HF readmissions, as well as HF-readmissions alone. Conclusions The most common cause of anemia in our study was iron-deficiency; almost half of the patients were iron deficient despite treatment, suggesting that oral iron may not be sufficient to reverse anemia. Anemia regardless of etiology was associated with adverse outcomes.

Pulmonary arterial hypertension (PAH) is a progressive, fatal vasculopathy that clinically manifests as increased pulmonary vascular resistance and elevation of pulmonary arterial pressures, ultimately leading to right heart failure and death. Median untreated survival period is 2.8 years, with a survival rate of 34% at 5 years before the availability of epoprostenol.1 Parenteral prostacyclin therapy is arguably the most effective and longest Food and Drug Administration-approved class of drugs for PAH and has been included in guidelines for treatment of PAH for almost 20 years. Intravenous epoprostenol as Flolan® remains the only drug that has demonstrated a survival advantage (Figure 1).2 Despite this demonstration of survival advantage and early evidence in its ability to improve a majority (70%) of patients to a point where they no longer required active listing for lung transplantation,3 epoprostenol or other infusion agents have consistently been shown to be withheld or underutilized in patients with advanced PAH.45 This apparent paradox as well as significant successful prostacyclin therapy in a variety of PAH patients6–8 forms the basis of our discussion on the role of infusion prostacyclins in modern management of PAH.

Purpose There are conflicting reports on the effect of donor-recipient HLA-DR matching in heart transplantation. Studies have shown HLA-DR matching reduces the incidence of graft rejection within the first year and improves short term graft survival It is not known if HLA-DR matching impacts long term outcomes. We sought to analyze the effect of HLA-DR mismatch on long term survival, and also explain possible mechanisms. Methods All adult heart transplants performed at our institution from 2000 to 2010 were retrospectively reviewed. Multi-organs, patients who expired within the first year after transplant and those with missing data were excluded. Patients were grouped according to number of HLA-DR mismatches: 0, 1 or 2. We analyzed allograft function [using most recent ejection fraction (EF)], development of significant (ISHLT grade ≥2) cardiac allograft vasculopathy (CAV) and survival. ANOVA used for analysis. Kaplan-Meier survival curves generated. P value Results 172 heart transplant recipients were included in the analysis. HLA-DR mismatch status was as follows: 9 (5.2%) had 0, 63 (36.6%) had 1, and 100 (58.1%) had 2 mismatches. There were more men in the group with 2 mismatches (82% vs 74.6% vs 66.7%, P Conclusion In our cohort, HLA-DR mismatches did not influence graft function, development of and severity of angiographically significant CAV. There was no impact on long term patient survival. HLA-DR matching prior to heart transplant may not be justified given the increased cost and logistical burden of HLA matching and longer cold‐ischemic times that may result from reliance on tissue typing.

The new allocation criteria classify patients on veno-arterial extracorporeal membranous oxygenation (VA-ECMO) as the highest priority for receiving orthotopic heart transplantation (OHT) especially if they are considered not candidates for ventricular assist devices. The outcomes of patients who receive ventricular assist devices (VADs) after being listed for heart transplantation with VA-ECMO is unknown. We analyzed 355 patients listed for OHT with VA-ECMO from the United Network for Organ Sharing database from 2006 to 2014. Univariate and multivariate Cox proportional-hazards models were used to determine the contribution of prognostic variables to the outcome. Thirty-three patients (9.3%) received VADs (15 dischargeable, 7 non-dischargeable VADs). The VAD and non-VAD groups had similar listing characteristics except that the VAD group were more likely to have non-ischemic cardiomyopathy (48.5% vs. 25.2%), and less likely to be obese (6.1% vs. 25.2%) or have a history of prior organ transplant (3% vs. 31.1%). Patients who underwent VAD implantation had more days on the list (median 189 vs. 14 days) compared to the non-VAD group. Amongst the patients who had VADs, (25/33) 75.5% patients were subsequently transplanted with similar post-transplant survival compared to the non-VAD group (72% vs. 60.5%, p = 0.276). Predictors of one-year post-transplant mortality included panel reactive antibodies (PRA) class I &ge, 20%, recipient smoking history, increased serum creatinine and total bilirubin. Therefore, a small proportion of patients listed for transplantation with VA ECMO undergo VAD implantation. Their waitlist survival is better than non-VAD group but with similar post-transplant survival.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.

Purpose Dobutamine stress echo (DSE) carries a class IIa recommendation for screening of cardiac allograft vasculopathy (CAV). Positive DSEs have a modest ability to predict development of CAV, but normal DSE has a low negative predictive value for CAV. Ability of a positive DSE to predict outcomes is controversial. Outcomes following a normal DSE have not been assessed in large, modern cohorts. We sought to analyze the prognostic value of DSE in heart transplant recipients. Methods All adult heart transplants performed at our institution from 2000 to 2010 were reviewed. Multi organ, recipients who expired within the first year, and those who did not have a DSE were excluded. Patients were grouped according to their DSE result and CAV grade and survival were analyzed. We also analyzed outcomes in patients with a normal DSE and predictors for CAV in this cohort. Unpaired t-test used for analysis. Kaplan-Meier survival curves generated. P value Results 179 (mean age 56.6 yrs, 77.6% male) heart transplant recipients were included. 26 (14.5%) patients had a positive DSE. 143 (79.9%) patients subsequently underwent coronary angiography [median duration 9 (1.1 - 17.2) yrs after transplant]. Positive DSE was associated with development of angiographically significant CAV (40% vs 12.2%, P=0.0015) and higher grade CAV (mean grade 1.2±1.2 vs 0.6±0.8, P=0.0077). Those with a positive DSE had a worse 10 yr survival (45.8% vs 68.7%, P=0.0092). Of those with a normal DSE, 15 (12.2%) developed significant CAV. In the normal DSE cohort, there were no differences in demographics, CMV mismatch status, HLA DR mismatch level or donor age between those who developed significant CAV and those who did not. Following a normal DSE, there was no difference in 10 yr survival (80% vs 77.7%, P=0.88) between those who developed and did not develop CAV. Conclusion Positive DSE is associated with development of significant CAV and worse survival. Normal DSE is associated with better survival, regardless of development of CAV.

Background Approximately 2–3% of patients undergoing advanced heart failure therapies such as left ventricular assist devices (LVAD) and orthotropic heart transplantation (OHT) have chemotherapy-related cardiomyopathy, according to analyses of large databases such as United Network for Organ Sharing (UNOS) or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registries. While these studies have shown similar survival outcomes post-interventions, these databases by definition exclude patients referred for advanced therapies but do not receive them, and thus there is little data on overall outcomes of such patients. Given the lack of nuance in the diagnoses in large registries and the possibility that many cancer treatment-related cardiomyopathy (CCMP) patients might be misclassified by the generic “non-ischemic” or “dilated” cardiomyopathies, we investigated the incidence and clinical outcomes of CCMP patients among advanced heart failure (HF) referrals at a single high volume institution. Methods All referrals from 2013 to 2016 were evaluated for type of cardiomyopathy, with careful chart review. Outcomes such as LVAD, OHT and death were compared between CCMP and other cardiomyopathies. Results Of 553 referrals for advanced HF, 19 (3.4%) were for CCMP. There was a higher percentage of patients receiving advanced therapies in the CCMP vs. non-ischemic cardiomyopathy (NICMP) and ischemic cardiomyopathy (ICMP) (42.1% vs 30.2% vs 33.6%, not significant). Of the CCMP patients, 3 had OHT directly, 2 had LVAD followed by OHT, and 3 had LVADs as bridge to candidacy or destination therapy. Fifty-eight percent of the CCMP did not receive LVAD or OHT compared to 69.8% and 66.3 of the NICMP and ICMP, respectively (p = 0.0388). Independent of type of advanced therapy, survival was significantly higher in the CCMP group compared to NICMP and ICMP (93.3% vs 84.8% vs 73.8%, respectively P = 0.0021 for 1 year, 93.3% vs 76.2% vs 58.3%, respectively, P =

The phase 4 COMPASS-3 study evaluated whether a singular endpoint produces clinically meaningful outcomes in patients with pulmonary arterial hypertension (PAH). The relationship between cardiac magnetic resonance imaging (cMRI)-derived parameters and right heart catheterization (RHC) measurements was also examined. In COMPASS-3 (ClinicalTrials.gov NCT00433329), 100 patients with PAH received bosentan monotherapy for 16 weeks. Patients continued monotherapy if their 6-min walk distance (6MWD) was ≥380 m, or otherwise received add-on sildenafil for an additional 12 weeks. 6MWD, RHC, and cMRI were performed at baseline, week 16, and week 28 (6MWD and cMRI). Baseline median 6MWD was 274 m and 82% of patients had WHO Functional Class III/IV. At week 16, 17% (n = 16) of remaining patients achieved the 6MWD threshold and 78 (83%) did not. In the intention-to-treat population, median 6MWD increased significantly relative to baseline (week 16 = 308 m; week 28 = 327 m; P

Purpose Persistent hyponatremia after LVAD implantation is not uncommon in patients with end-stage heart failure (HF) and maybe associated with adverse outcomes . The etiology of hyponatremia in HF patients is multifactorial. It is generally thought that with restoration of hemodynamics , hyponatremia would resolve after LVAD implantation. We sought to determine the etiology of persistent hyponatremia after LVAD implantation. Methods We performed a retrospective analysis of patients with end-stage HF who received a continuous-flow LVAD and subsequently underwent right heart catheterization (RHC) to assess invasive hemodynamics and for speed optimization. Data was collected concurrently on invasive hemodynamics, medication usage and basic metabolic panel . Hyponatremia was defined as serum sodium level Results We included 143 patients in our study. RHC was performed within 6 months from LVAD implantation in 70% of the population, the median time was 199 days. Patients with hyponatremia had a mean sodium of 130.5 mEq/L compared to 139.8 mEq/L in patients with normonatremia, p-value Conclusion Persistent hyponatremia after LVAD implantation does not appear to be related to low cardiac output state, volume expansion or depletion, RV dysfunction, use of ACEI or ARBs, loop diuretics or renal function. Hyponatremia may be an independent marker of adverse outcomes after LVAD implantation.

Purpose There is paucity of data on assessment of invasive hemodynamics via right heart catheterization (RHC) after LVAD implantation and association with outcomes. We sought out to define if RV dysfunction, persistent volume overload and low cardiac output state defined via invasive hemodynamics is associated with adverse 1-year outcomes. Methods We conducted a retrospective analysis of end-stage HF patients who underwent continuous-flow LVAD implantation and subsequent RHC to determine invasive hemodynamics. 1-year outcomes including mortality, all-cause readmission and HF readmissions were assessed after index RHC. Definitions included low cardiac output state (CI 12 mm Hg), moderate RV dysfunction (RAP/pulmonary capillary wedge pressure (PCWP) >0.75) and severe right ventricle dysfunction (RA/PCWP >1). Results A total of 142 patients underwent invasive hemodynamics after LVAD implantation. The median time from LVAD implantation to RHC was 6 months. Conclusion RV dysfunction defined using invasive hemodynamic criteria did not predict adverse 1-year outcomes. RAP > 12 mmHg indicative of persistent volume overload after LVAD implantation was significantly associated with increase HF readmissions at 1 year.

Background Pulmonary arterial hypertension (PAH) is a potentially serious cause of dyspnea and exercise limitation in patients with HIV infection. In this trial, we propose using exercise MRI in conjunction with cardiopulmonary testing to delineate PAH from other causes of cardiovascular dysfunction, identify individuals with exercise-induced PAH who are at high risk of developing resting PAH, and provide longitudinal estimates of progression of PAH and right ventricular function. Methods In this prospective observational study, HIV patients with dyspnea and exercise limitation in the absence of identifiable causes and those who meet the inclusion criteria will be enrolled based on resting pulmonary artery pressure (≤ or >40 mmHg) on a screening echocardiogram and exercise limitation on the Modified Medical Research Council dyspnea scale. Patients without evidence of resting PAH will be enrolled into both rest and exercise MRI and cardiopulmonary testing protocol, whereas patients with evidence of PAH on resting echocardiograms will undergo only resting cardiac MRI studies to evaluate right ventricular function and fibrosis. Both patient subgroups will be followed for 24 months to obtain longitudinal progression of the disease. In a sub-study, we will further analyze inflammatory variables that may predict these changes, thus allowing early identification of these patients. Implications and conclusions This trial will be the first study to provide an understanding of the mechanisms underpinning the functional deterioration of the right ventricle in patients with HIV and will impart insight into the immune mediators of PAH progression and right ventricular functional deterioration in patients with HIV-PAH.

Patients bridged to transplant (BTT) with continuous-flow left ventricular assist devices (CF-LVADs) have increased in the past decade. Decision support tools for these patients are limited. We developed a risk score to estimate prognosis and guide decision-making. We included heart transplant recipients bridged with CF-LVADs from the United Network for Organ Sharing (UNOS) database and divided them into development (2,522 patients) and validation cohorts (1,681 patients). Univariate and multivariate Cox proportional hazards models were performed. Variables that independently predicted outcomes (age, African American race, recipient body mass index [BMI], intravenous [IV] antibiotic use, pretransplant dialysis, and total bilirubin) were assigned weight using linear transformation, and risk scores were derived. Patients were grouped by predicted posttransplant mortality: low risk (≤ 38 points), medium risk (38-41 points), and high risk (≥ 42 points). We performed Cox proportional hazards analysis on wait-listed CF-LVAD patients who were not transplanted. Score significantly discriminated survival among the groups in the development cohort (6.7, 12.9, 20.7; p = 0.001), validation cohort (6.4, 10.1, 13.6; p < 0.001), and ambulatory cohort (6.4, 11.5, 17.2; p < 0.001). We derived a left ventricular assist device (LVAD) BTT risk score that effectively identifies CF-LVAD patients who are at higher risk for worse outcomes after heart transplant. This score may help physicians weigh the risks of transplantation in patients with CF-LVAD.

Background There is paucity of data on assessment of invasive hemodynamics via right heart catheterization (RHC) after LVAD implantation and association with outcomes. We sought out to define if right ventricular (RV) dysfunction, persistent volume overload and low cardiac output state defined via invasive hemodynamics is associated with adverse 1-year outcomes. Methods We conducted a retrospective analysis of end-stage heart failure (HF) patients who underwent continuous-flow LVAD implantation and subsequent right heart catheterization (RHC) to determine invasive hemodynamics. 1-year outcomes including mortality, all-cause readmission and HF readmissions were assessed after index RHC. Definitions included low cardiac output state (CI) 12 mm Hg), moderate right ventricle (RV) dysfunction (RAP/pulmonary capillary wedge pressure (PCWP) >0.75) and severe right ventricle dysfunction (RA/PCWP >1). Chi-square for categorical variables and Student's T-test for continuous variables were used to determine significant differences in each group. Results A total of 142 patients underwent invasive hemodynamics after LVAD implantation. The median time from LVAD implantation to RHC was 6 months. RAP/PCWP ratio was not predictive of adverse outcome and although RAP > 12 mmHg was not associated with increased mortality it was associated with significantly increased HF readmissions at 1 year. Discussion RV dysfunction defined using invasive hemodynamic criteria did not predict adverse 1-year outcomes. RAP > 12 mmHg indicative of persistent volume overload after LVAD implantation was significantly associated with increase HF readmissions at 1 year.

Purpose The gold standard to determine adequate LV unloading after LVAD implantation remains invasive hemodynamics via right heart catheterization (RHC). Echocardiogram parameters have been used as surrogates for adequate LV unloading as part of LVAD speed optimization protocols. We sought to determine if echocardiogram can be used to precisely predict adequate LV unloading as compared to invasive hemodynamics. Methods Single-center retrospective analysis of all patients that underwent LVAD implantation followed by pump speed optimization using echocardiogram and RHC concomitantly in the catheterization laboratory. Adequate LV unloading was defined as CI >=2.2 and PCWP Results Our sample included 142 patients with a mean age of 57.5. Significant parameters associated with LV unloading are shown in table 1. Not significant parameters include: E/A, E/e’ and PASP estimate. Conclusion Our study shows that echocardiogram is able to determine adequate LV unloading with enough specificity only when it shows very significant changes from the baseline echocardiogram. If the cutoffs are not met, patient would benefit from RHC to determine with confidence if LV is adequately unloaded and if necessary, LVAD speed optimization.

Background Pulmonary arterial hypertension (PAH) is a progressive disease with lung transplantation as the only option for those patients refractory to medical therapy. Although several equations have been developed to predict PAH patient survival, it is unclear whether they can predict survival for patients awaiting transplantation. Methods Data were analyzed on 827 patients listed since 1991 on the Scientific Registry of Transplant Recipients. Overall survival and survival for patients listed prior to and after January 1, 2006 was estimated using the Kaplan–Meier (K-M) method and compared with predicted survival from the pulmonary hypertension connection (PHC) and lung allocation system (LAS) equations. A new equation using a novel model selection algorithm for correlated covariates and missing data was developed using clinical factors and variables in the LAS score. Model validation statistics were calculated and averaged across 500 bootstrap resamples within each of 5 imputation data sets. K-M with 95% confidence intervals and receiver–operator characteristic (ROC) curves assessed model performance. Results PHC predicted overall survival but underestimated and overestimated survival for those listed pre- and post-2006, respectively. The best model included baseline 6-minute walk distance (6MWD), invasive cardiac output and resting oxygen requirement (O 2 ). Factors associated with 1-year waitlist survival included: resting O 2 amount; invasive hemodynamics; 6MWD; and functional class. The new equation by ROC analysis outperformed the LAS and PHC equations. Conclusions Current prediction models overestimate survival for PAH patients listed for transplant in the LAS era. This new survival equation can help guide clinicians caring for PAH patients with progression of disease requiring transplant.

Pulmonary arterial hypertension (PAH) is a specific, rare disease characterized by a well-described pattern of pulmonary vascular remodeling. The elevated pulmonary artery pressure in PAH results in increased right ventricular afterload, which, if untreated, leads rapidly to right ventricular failure and death. Recent marked expansion in knowledge about PAH has resulted in the development of effective therapies that improve quality of life and survival. However, delays in diagnosis and suboptimal treatment remain significant barriers to achieving optimal patient outcomes. Continued success in raising PAH awareness, earlier diagnosis, and the availability of new therapies mean a promising future for PAH patients.

Pulmonary hypertension (PH) in the setting of left side heart disease is associated with adverse outcomes. The exact prevalence of PH in the different pathologies that affect the left ventricle, however, is difficult to access with the current literature. The lack of a standard definition of PH in older studies, the different modalities to assess pulmonary artery pressures and the varying disease severity, all account for the great variability in the reported prevalence of PH. PH can accompany heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) as well as mitral and aortic valve disease; in any of these instances it is important to recognize whether the elevation of pulmonary pressures is driven by elevated left ventricular pressures only (isolated post-capillary PH) or if there is an accompanying remodeling component in the pulmonary arterioles (combined post-capillary and pre-capillary PH). The objective of this review is to describe the definitions, prevalence and the risk factors associated with the development of PH in the setting of HFrEF, HFpEF and valvular heart disease.

Tracing the history of nomenclature and classification of pulmonary hypertension reveals a complex journey spanning three centuries. Initial observations regarding the functions of cardiopulmonary systems served as a platform for the tremendous progress achieved in the past century, with the most significant event being the introduction and standardization of right heart catheterization. The advent of the pulmonary hypertension epidemic due to aminorex galvanized the medical community to learn more about this fatal disease, major outcome being the formation of the PPH Registry from which the natural history, epidemiology and clinical features were gathered. These initial efforts paved the way for tremendous advances which followed in screening, diagnosis, and discovery of targeted therapies. A critical contributor to the progress is the introduction and evolution in nomenclature and classification system created from the need to standardize terminology and provide structure to serve as framework for research and patient care. This chapter will discuss the key events leading to the present day nomenclature scheme and classification system for pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary pressures and chronic right heart failure. Therapies for moderate and severe PAH include subcutaneous (SQ) and intravenous (IV) prostanoids that improve symptoms and quality of life. However, treatment compliance can be limited by severe side effects and complications related to methods of drug administration. Inhaled prostanoids, which offer the advantage of direct delivery of the drug to the pulmonary circulation without need for invasive approaches, may serve as an alternative for patients unable to tolerate SQ/IV therapy. In this retrospective cohort study we collected clinical, hemodynamic, and functional data from 18 clinically stable patients with World Health Organization group I PAH seen in 6 large national PAH centers before and after transitioning to inhaled treprostinil from IV/SQ prostanoids. Before transition 15 patients had been receiving IV or SQ treprostinil (mean dose 73 ng/kg/min) and 3 patients had been on IV epoprostenol (mean dose 10 ng/kg/min) for an average duration of 113 ± 80 months. Although most patients who transitioned to inhaled treprostinil demonstrated no statistically significant worsening of hemodynamics or 6-minute walk distance, a minority demonstrated worsening of New York Heart Association functional class over a 7-month period. In conclusion, although transition of patients from IV/SQ prostanoids to inhaled treprostinil appears to be well tolerated in clinically stable patients, they should remain closely monitored for signs of clinical decompensation.

Pulmonary arterial hypertension (PAH) is a disabling, progressive disease. The past decade has seen an explosion in the available therapies for the management of PAH. Choosing appropriate pharmacotherapy can be a daunting task for the practitioner, as no head-to-head comparisons between drugs have been published. This article aims to assist the practitioner in developing an evidence-based, rational pharmacologic treatment algorithm for the management of patients with PAH. Currently approved pharmacotherapy and the pivotal trials that led to approval for the respective agents are reviewed. Common dilemmas in the treatment of PAH for which strong evidence is lacking are discussed.

The American College of Cardiology Foundation (ACCF), Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and the American Association for Thoracic Surgery, along with key specialty and subspecialty societies, conducted an update of the appropriate use criteria (AUC) for coronary revascularization frequently considered. In the initial document, 180 clinical scenarios were developed to mimic patient presentations encountered in everyday practice and included information on symptom status, extent of medical therapy, risk level as assessed by noninvasive testing, and coronary anatomy. This update provides a reassessment of clinical scenarios the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document, and the definition of appropriateness was unchanged. The technical panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate and likely to improve patients' health outcomes or survival. Scores of 1 to 3 indicate revascularization is considered inappropriate and unlikely to improve health outcomes or survival. Scores in the mid-range (4 to 6) indicate a clinical scenario for which the likelihood that coronary revascularization will improve health outcomes or survival is uncertain. In general, as seen with the prior AUC, the use of coronary revascularization for patients with acute coronary syndromes and combinations of significant symptoms and/or ischemia is appropriate. In contrast, revascularization of asymptomatic patients or patients with low-risk findings on noninvasive testing and minimal medical therapy are viewed less favorably. The technical panel felt that based on recent studies, coronary artery bypass grafting remains an appropriate method of revascularization for patients with high burden of coronary artery disease (CAD). Additionally, percutaneous coronary intervention may have a role in revascularization of patients with high burden of CAD. The primary objective of the appropriate use criteria is to improve physician decision making and patient education regarding expected benefits from revascularization and to guide future research.

A panel of experts convened by telephone on April 20, 2011 to discuss their experiences and recommendations regarding diagnosis and management of patients with Group 2 PH. The conversation was facilitated by Myung Park, MD, Associate Professor of Medicine and Director, Pulmonary Vascular Disease Program, Division of Cardiology at University of Maryland School of Medicine and guest editor of this issue. The participants were Rene Alvarez, MD, Associate Professor of Medicine and Director, Advanced Heart Failure/Pulmonary Hypertension Outreach Program, University of Pittsburgh School of Medicine; Teresa De Marco, MD, Professor of Medicine, Director, Heart Failure and Pulmonary Hypertension Program and Director, Heart Transplantation, University of California San Francisco Medical Center; Marc Semigran, MD, Medical Director of the Heart Failure and Cardiac Transplant Program at the Massachusetts General Hospital Center and Associate Professor of Medicine at Harvard Medical School; and Ivan Robbins, MD, Assistant Professor of Medicine and Director, Lung Transplant Program, Vanderbilt University Medical Center.

Background Hyponatremia is a known predictor of adverse outcomes in patients with chronic systolic heart failure (HF). It is unclear if persistent hyponatremia after LVAD implantation has an adverse influence on outcomes including mortality and recurrent hospitalizations. Methods We conducted a retrospective analysis of patients who received a continuous-flow LVAD from 2008-2017. Sodium levels were assessed prior to surgery and at discharge. Hyponatremia was defined as sodium Results Our population consisted of 143 patients, mean age 57.4 (range 25-79), 75.5% of male gender and 55% had an ischemic etiology of HF. Mean sodium level in patients with persistent hyponatremia at discharge was 132±2.7 mEq/L compared to 138.3±2.7 mEq/L in patients with normonatremia, p-value table 1 ). Discussion Hyponatremia is thought to be the pathophysiological sequela of progressive heart failure. LVAD implantation often restores normal hemodynamics and leads to correction of pre-existing hyponatremia in HF patients. However, persistent hyponatremia at the time of discharge is not uncommon and is associated with higher 1-year mortality. Further studies are needed to elucidate the etiology of hyponatremia in this population.

Background Persistent hyponatremia after LVAD implantation is not uncommon in patients with end-stage heart failure (HF) and maybe associated with adverse outcomes. The etiology of hyponatremia in HF patients is multifactorial including - low cardiac output state, volume expansion, impaired free water excretion due to renal insufficiency and use of loop diuretics. It is generally thought that with restoration of hemodynamics hyponatremia would resolve after LVAD implantation. We sought to determine the etiology of persistent hyponatremia after LVAD implantation. Methods We performed a retrospective analysis of patients with end-stage HF who received a continuous-flow LVAD and subsequently underwent right heart catheterization (RHC) to assess invasive hemodynamics and for speed optimization. Data was collected concurrently on invasive hemodynamics, medication usage and basic metabolic panel. Hyponatremia was defined as serum sodium level 12 mmHg, volume depletion defined by RAP 0.75 (moderate) and >1.0 (severe), partially unloaded left ventricle (LV) defined by PCWP > 15, use of angiotensin converter enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), use of loop diuretics and renal function measured by estimated glomerular filtration rate (GFR). Each of the factors were compared between patients with hyponatremia and normal sodium levels. Results We included 143 patients in our study. RHC was performed within 6 months from LVAD implantation in 70% of the population, the median time was 199 days. Patients with hyponatremia had a mean sodium of 130.5 mEq/L compared to 139.8 mEq/L in patients with normonatremia, p-value table 1 ). One-year mortality and all-cause readmissions (from time of RHC) were both higher in the hyponatremia group, p-values of 0.012 and 0.023 respectively. Discussion Persistent hyponatremia after LVAD implantation does not appear to be related to low cardiac output state, volume expansion or depletion, RV dysfunction, use of ACEI or ARBs, loop diuretics or renal function. Hyponatremia may be an independent marker of adverse outcomes after LVAD implantation.