Evidence Of Right Ventricular Dysfunction Research Articles

Intermediate-high risk pulmonary embolism: When teamwork really matters

Pulmonary embolism is a common disease associated with significant morbidity and mortality. Existing validated risk stratification tools have enabled the rapid identification of patients with low versus high-risk pulmonary embolism. Intermediate-high risk pulmonary embolism is defined as pulmonary embolism with haemodynamic stability, evidence of right ventricular dysfunction and elevated cardiac biomarkers. The therapeutic management of intermediate-high risk pulmonary embolism in the acute setting is challenging as these patients are often unwell, but do not fulfil criteria for high-risk pulmonary embolism. Although current guidelines recommend prompt first-line treatment with systemic anticoagulation and monitoring for deterioration, alternative strategies are being increasingly considered in this cohort. These include systemic or catheter-directed thrombolysis, surgical embolectomy, and mechanical circulatory support. In this case series, we discuss three cases of intermediate-high risk pulmonary embolism with a focus on multidisciplinary decision making in clinical management. Following on from this, we provide a brief narrative review of the current literature and guidelines surrounding this topic, considering the risks and benefits of alternative therapy options on patient outcomes.

Right Ventricular Function and Pulmonary Coupling in Patients With Heart Failure and Preserved Ejection Fraction

BackgroundLimited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). ObjectivesThis study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. MethodsThis study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. ResultsOverall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. ConclusionsWorsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Right ventricular cardiac resynchronization therapy in patients with right ventricular conduction delay and heart failure

Right ventricular cardiac resynchronization therapy in patients with right ventricular conduction delay and heart failure

Diagnostic accuracy of multiorgan point-of-care ultrasound compared with pulmonary computed tomographic angiogram in critically ill patients with suspected pulmonary embolism.

Critically ill patients have a higher incidence of pulmonary embolism (PE) than non-critically ill patients, yet no diagnostic algorithm has been validated in this population, leading to the overuse of pulmonary artery computed tomographic angiogram (CTA). This study aimed to comparatively evaluate the diagnostic accuracy of point-of-care ultrasound (POCUS) combined with laboratory data versus CTA in predicting PE in critically ill patients. A prospective diagnostic accuracy study. Critically ill patients with suspected acute PE undergoing CTA were prospectively enrolled. Demographic and clinical data were collected from electronic medical records. Blood samples were collected, and the Wells and revised Geneva scores were calculated. Standardized multiorgan POCUS and CTA were performed. The discriminatory power of multiorgan POCUS combined with biochemical markers was tested using ROC curves, and multivariate analysis was performed. A total of 88 patients were included, and 37 (42%) had PE. Multivariate analysis showed a relative risk (RR) of PE of 2.79 (95% CI, 1.61-4.84) for the presence of right ventricular (RV) dysfunction, of 2.54 (95% CI, 0.89-7.20) for D-dimer levels >1000 ng/mL, and of 1.69 (95% CI, 1.12-2.63) for the absence of an alternative diagnosis to PE on lung POCUS or chest radiograph. The combination with the highest diagnostic accuracy for PE included the following variables: 1- POCUS transthoracic echocardiography with evidence of RV dysfunction; 2- lung POCUS or chest radiograph without an alternative diagnosis to PE; and 3- plasma D-dimer levels >1000 ng/mL. Combining these three findings resulted in an area under the curve of 0.85 (95% CI, 0.77-0.94), with 50% sensitivity and 96% specificity. Multiorgan POCUS combined with laboratory data has acceptable diagnostic accuracy for PE compared with CTA. The combined use of these methods might reduce CTA overuse in critically ill patients.

Exploring the pathophysiologic basis of constrictive pericarditis of Kohlmeier Degos disease: A case series and review of the literature

Kohlmeier-Degos Disease is a unique thrombotic microvascular and arteriopathic vasculopathy that is highly selective in the organs it targets. It invariably involves the skin and can be a purely cutaneous process. It affects both the microvasculature and the arterial system ranging from a thrombogenic microangiopathy to a fibrointimal obliterative arteriopathy with an accompanying background of extravascular fibrosis. A potentially lethal complication of Kohlmeier-Degos disease is constrictive pericarditis and pleuritis. We present three male patients, ages 26 years, 46 years and 58 years of age with established cutaneous and gastrointestinal Kohlmeier-Degos disease who developed progressive pericarditis which in two necessitated a pericardiectomy. There are 6 other reported cases, 5 in men, with restrictive symptoms developing on average 6 years following the onset of skin disease and all with gastrointestinal involvement. Half of the patients died within one year following the diagnosis of cardiopulmonary restrictive disease. The restrictive symptoms developed within 12 months, 2 years and 11 years following the initial skin presentation. In one patient this complication developed despite receiving eculizumab, indicative that this extravascular fibrosing reaction was not complement mediated as opposed to the thrombotic microvascular component of the disease which is C5b-9 mediated. Two of the three patients had evidence of right ventricular dysfunction. Two of our patients died within 1 year of developing constrictive pericarditis due to progressive cardiopulmonary failure. A profibrogenic process resembling scleroderma was seen given the degree of smooth muscle actin staining along with a mirror image reduction in CD34 expression within the fibrotic pleura and pericardium. There was significant upregulation in type I interferon signaling in cases tested as revealed by the degree of staining for MXA, the surrogate type I interferon marker. We propose that excessive type I interferon signaling results in the influx of monocyte derived dendritic cells with subsequent transdifferentiation into potent collagen producing myofibroblasts. We believe that targeting and suppressing type I interferon signaling should be a cornerstone of early therapy in patients with Kohlmeier- Degos disease to prevent pleural and pericardial fibrosis.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) remains significantly underdiagnosed in patients with a history of pulmonary embolism. These patients complain of persistent shortness of breath and present with hypoxemia despite proper anticoagulation. Further investigation reveals evidence of right ventricular dysfunction on echocardiogram, which progresses to right heart failure. CTEPH is associated with a significant increase in patient morbidity and mortality if left untreated. This article offers an approach for the timely recognition of this condition, in addition to suggesting a management protocol with an emphasis on the role of interventional radiology and balloon pulmonary angioplasty.

622 Long term prognostic impact of right ventricular dysfunction in patients with COVID-19

AimsThe characteristics and clinical course of hospitalized patients with Coronavirus disease 2019 (COVID-19) have been widely described, while long-term data are still poor. The aim of this study was to evaluate the long-term clinical outcome and its association with right ventricular (RV) dysfunction in hospitalized patients with COVID-19.Methods and resultsThis was a retrospective multicentre study of consecutive COVID-19 patients hospitalized at seven Italian Hospitals from 28 February to 20 April 2020. The study population was divided into two groups according to echocardiographic evidence of RV dysfunction defined by tricuspid annular plane systolic excursion (TAPSE) value <17 mm in accordance with the current guidelines. The primary study outcome was 1-year mortality. The study population consisted of 224 patients (mean age 69 ± 14, male sex 62%); RV dysfunction was diagnosed in 63 cases (28%). Patients with RV dysfunction were older (75 vs. 67 years, P < 0.001) and showed a higher prevalence of coronary artery disease (27% vs. 11%, P = 0.003), heart failure (5% vs. 22%; P < 0.001), chronic obstructive pulmonary disease (13% vs. 38%; P < 0.001), and chronic kidney disease (12% vs. 39%; P < 0.001). Left ventricular ejection fraction (LVEF) was significantly lower in patients with RV dysfunction that in those without (55% vs. 50%; P < 0.001). The rate of mortality at 1-year was significantly higher in patients with RV dysfunction as compared with those without (67% vs. 28%; P ≤ 0.001). After propensity score matching, patients with RV dysfunction showed a significantly lower long-term survival than patients without RV dysfunction (62% vs. 29%, P < 0.001). At multivariable Cox regression analysis, TAPSE, LVEF and acute respiratory distress syndrome during the hospitalization were independently associated with 1-year mortality (Table).ConclusionsRV dysfunction is a relatively common finding in hospitalized patients with COVID-19 and is independently associated with an higher risk of mortality at one-year follow-up.

Predictors of mortality in patients with intermediate risk pulmonary embolism

Abstract Introduction Information about treatment and outcome of patients with pulmonary embolism (PE) intermediate risk remains limited. Little is known about the benefits of reperfusion therapy in patients with intermediate risk PE and evidence of right ventricular dysfunction. Objective To evaluate clinical outcomes and predictors of mortality in patients admitted to ICU with pulmonary embolism and intermediate risk. Methods In a prospective single-center study 103 normotensive patients with an established diagnosis of pulmonary embolism confirmed by pulmonary CT were included. All patients met intermediate risk criteria according to the European Society of Cardiology guidelines (ESC 2019) for pulmonary embolism using severity index [PESI] with signs of right ventricular dysfunction and elevated cardiac biomarkers. The average age of patients was 67.6 years (95% CI, 65.1–70.5), 42 (41%) of them were men. Thrombolysis with standard dose of alteplase was performed in 54 (52%) patients. CT scan and echocardiography were done for all patients. Results Outcome data were collected for all patients through the 30-day and 180-day follow-up. During 30 days follow up 14 patients died (13,6%, 95% CI, 6,9–20%). The all-cause mortality rate after 180 days was 22,2% (95% CI, 13,5–31%) - 22 patient. In the thrombolysis group only 2 patients died after 180-day follow-up, mortality rate was 4,4% (95% CI, 1,7–10,6%), the mortality rate in patients not treated by thrombolysis was 40% (95% CI, 25,3–54,7%). Thrombolysis was associated with a significant decrease in mortality [OR 0.07 (95% CI, 0.01–0.31)]. In the thrombolysis group 2 patients (4.1%; 95% CI, 1.1–10%) had a non-fatal major bleeding event. The presence of chronic heart failure [OR 6 (95% CI, 1.8–20.2)] and previous stroke [OR 4.3 (95% CI, 0.9–21.1)] were higher among non-survivors when compared to survivors (p≤0.05). TAPSE less than 16 mm was found to be negatively associated with survival [OR 5.5 (95% CI, 0.9–40.3)], p=0.02. Conclusion In our study thrombolysis in patients with pulmonary embolism and intermediate-risk was associated with improved prognosis. Predictors of mortality were the presence of CHF, previous stroke and TAPSE of less than 16 mm. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier mortality curves. p&amp;lt;0.05

Overview of Ventricular Assist Devices and the Total Artificial Heart.

Patients with isolated left ventricular failure may have positive outcomes after being implanted with a left ventricular assist device. Unfortunately, almost half of patients with heart failure and reduced ejection fraction also have evidence of right ventricular dysfunction. For a subset of this population with severe biventricular failure, or those who develop right ventricular dysfunction after left ventricular assist device implantation, patients may necessitate biventricular assist devices or the total artificial heart. This overview of mechanical circulatory support devices will enhance nurses' ability to differentiate criteria for implantation, current practice, and outcomes with a focus on durable ventricular assist devices and the total artificial heart. A review of the literature involved searching CINAHL and PubMed databases using keywords biventricular assist devices, total artificial heart, and durable mechanical circulatory support. Results were narrowed to articles based on adults, 18 years or older. Seventy-eight relevant articles were identified, and 8 articles compared the durable biventricular assist devices. Similar patient outcomes were found when comparing the use of left ventricular assist devices as biventricular support versus the total artificial heart. The decision to implant the appropriate durable mechanical circulatory support for a patient in biventricular failure is complex and dependent on patient factors.

Detection of Right Ventricular Dysfunction in Acute Pulmonary Embolism By CT Scan: A Systematic Review and Meta-Analysis

Background: Right ventricular (RV) dysfunction is associated with higher mortality in patients with acute pulmonary embolism (PE). While precise definitions of RV dysfunction vary, up to 40% of patients with acute PE have evidence of RV dysfunction on echocardiography. The incremental utility of echocardiography for identifying RV dysfunction in acute PE is uncertain particularly when evidence of RV dysfunction is present on computed tomography (CT) pulmonary angiogram. However, the diagnostic utility of CT for detecting RV dysfunction is not well established; if CT is shown to have good diagnostic utility, it may reduce the need for routine urgent echocardiography and associated healthcare costs and resource use. We conducted a systematic review and meta-analysis to assess the diagnostic utility of CT scan findings for detecting RV dysfunction compared to echocardiography. Methods: Using a pre-specified protocol (Prospero ID: CRD42020187812) we systematically searched the MEDLINE and EMBASE databases from inception to April 2020. Studies of any design were included so long as they (i) included patients with acute PE diagnosed by CT scan and received an echocardiographic study within a reasonable timeframe and (ii) reported on test characteristics such that a 2x2 table could be constructed to compare the two diagnostic modalities with echocardiography considered the reference standard. Results were analyzed with the bivariate mixed-effects regression framework. Study quality was assessed with the QUADAS-2 risk of bias tool. Results: A total of 631 unique studies were identified by the search. After screening titles and abstracts and reviewing full texts in duplicate, 26 studies (n=3,404 patients) were eligible for inclusion. In individual studies, the average age (mean or median) of patients ranged from 41 to 70 years and 20% to 64.3% were female. The prevalence of RV dysfunction on echocardiography ranged studies from 22.6% to 85.7% and was 63.7% overall. The most common measurements on CT scan were increased RV/LV ratio (21 studies), pulmonary artery measurements (6 studies), RV dilatation or increased size (5 studies), measurements of vena cava size (3 studies), and coronary sinus size (2 studies). Other parameters included reflux of contrast into the inferior vena cava (IVC reflux, 4 studies) and interventricular septal deviation (5 studies). Different combinations of measurements were evaluated in 5 studies. Pooled analysis was performed for septal deviation, IVC reflux, and RV/LV ratio. In pooled analysis septal deviation had a sensitivity of 0.31 (95% CI=0.25- 0.38; I2= 51.6%) and a specificity of 0.98 (95% CI=0.90 - 1.00; I2= 46.9%). IVC reflux had a sensitivity of 0.75 (95% CI = 0.40 - 0.93; I2=95.9%) and specificity 0.75 (95% CI=0.47 - 0.93; I2= 91.1%). Where multiple RV/LV ratios were reported, we utilized the one with the highest sensitivity. The pooled sensitivity of increased RV/LV ratio was 0.83 (95% CI=0.78 - 0.87; I2= 82.9) while the pooled specificity was 0.75 (95% CI=0.66- 0.82; I2= 94.6) (Figure 1). Considering all RV/LV ratio studies, the summary receiver operating characteristic (SROC) curve had an area under the curve (AUC) of 0.86 (0.83-0.89) for identifying the presence of RV dysfunction present on echocardiography. Overall, most studies were considered at high risk of bias. Subgroup analyses demonstrated that sensitivity was significantly affected by the risk of bias for RV/LV ratio for all QUADAS-2 domains. Specificity was not affected by the risk of bias for any of the QUADAS-2 domains. Conclusions: Our results suggest CT imaging findings appear to have moderate to good diagnostic utility for detecting the presence of RV dysfunction in acute PE. With the exception of septal deviation there was significant heterogeneity amount included studies. Overall, increased RV/LV ratio had the best test characteristics (sensitivity 0.83, specificity 0.75 and AUC 0.86). However, the veracity of these findings is limited by the high risk of bias among included studies. Further analyses regarding the diagnostic utility of combinations of multiple CT findings are warranted. Figure 1 Disclosures Crowther: Pfizer: Speakers Bureau; Alnylam: Divested equity in a private or publicly-traded company in the past 24 months; CSL Behring: Speakers Bureau; Servier Canada: Membership on an entity's Board of Directors or advisory committees; Diagnostica Stago: Speakers Bureau; Asahi Kasei: Membership on an entity's Board of Directors or advisory committees; Precision Biologicals: Membership on an entity's Board of Directors or advisory committees; Hemostais Reference Laboratories: Honoraria. Siegal:BMS Pfizer: Honoraria; Bayer: Honoraria; Novartis: Honoraria; Leo Pharma: Honoraria; Portola: Honoraria.

Right Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension

Idiopathic pulmonary arterial hypertension (PAH) is a severe disease associated with a 20% 5-year mortality, often due to right heart failure. Recent studies suggest that compensatory changes in right atrial (RA) function may precede other clinical and echocardiographic evidence of right ventricular dysfunction. No prior prospective study has evaluated the role of RA emptying pattern as a prognostic marker of adverse clinical events in pediatric PAH. To demonstrate whether RA fractional emptying indices will prospectively predict risk of adverse clinical outcomes in pediatric PAH patients. Single-center, prospective cohort analysis of 41 patients with idiopathic or heritable PAH and 1:1 age and sex-matched controls with normal echo and electrocardiogram. Right atrial area (RAA) was measured just prior to tricuspid valve opening (RAAmax), at electrical p wave (RAAp), and just after tricuspid valve closing (RAAmin). Right atrial conduit fraction percent (RA cF%) was defined as the percentage of total RAA change happening prior to the electrical p wave= (RAAmax - RAAp)/(RAAmax - RAAmin) ∗ 100. Clinical worsening was analyzed with a predefined composite adverse event outcome. RA measurements were technically feasible in all study participants. The PAH patients (median age 11.9years) had decreased RA cF% compared with controls (P<.0001), and PAH subjects with lower RA cF% demonstrated higher right ventricular systolic (R=-0.49, P=.019) and end-diastolic (R=-0.52, P=.012) pressure than those with higher RA cF%. Sixteen subjects had a clinical event. Right atrial cF% (hazard ratio=0.09; P<.001) was highly prognostic for risk of adverse clinical event with area under the curve=0.90 on receiver operating characteristic curve analysis (median 3.2-year follow-up). Right atrial conduit phase emptying is significantly altered in pediatric PAH. Within the PAH population, decreased RA cF% was prognostic for risk of clinical worsening. The combination of accuracy and ease of measurement could make RA cF% a clinically useful, noninvasive biomarker of early right heart failure and risk of disease progression in pediatric PAH.

Acute venous thromboembolism in a limited resource healthcare system: Mitigating management challenges

Objective: The study's aim was to categorize patients' risk profiles, management options, and strategies to mitigate clinical practice challenges in a limited resource setting. Materials and Methods: We retrospectively reviewed the medical records of patients with acute venous thromboembolism (VTE) entered in a prospective database at our center from August 2014 to July 2021. Results: Twenty-two of 708 admitted patients were diagnosed with VTE for an incidence of 3.1%. The mean age was 63.7 ΁ 14.7, range 30-89, mean body mass index 31.5 ΁ 6.7 and 54.5% were female. Six (27.3%) patients had deep-vein thrombosis (DVT), 14 (63.6%) pulmonary embolism (PE) and 2 (9.1%) DVT/ PE. Dyspnea (68.2%) and leg swelling (63.6%) were the most frequent presenting symptoms. Hypoxemia with oxygen saturation <90 and cardiogenic shock was present in 27.3% and 13.6%, respectively. Due to limited access to computer tomography pulmonary angiogram (CTPA), transthoracic echocardiogram (TTE) was utilized to aide diagnosis and was performed in 14 (87.5%) patients with PE. All 14 patients showed evidence of right ventricular dysfunction, 78.5% had moderate-to-severe pulmonary hypertension and 57.1% right heart thrombus. 4 patients with DVT were treated as outpatients. All inpatients were anticoagulated with either unfractionated heparin or low-molecular-weight heparin and transitioned to Vitamin K antagonist or direct oral anticoagulant. The primary treatment duration was 3-6 months. The mean duration of follow-up was 17.5 ΁ 14.7 months. Hospital mortality was 16.7% (3/18), 30 days mortality 18.2% (4/22) and 6 months all-cause mortality 31.8% (7/22). All patients with late deaths had moderate-to-severe pulmonary hypertension. Conclusion: TTE in the absence of CTPA is a useful alternative diagnostic tool in the management of acute PE in limited-resource settings. It may also aid prognostication through estimation of pulmonary artery pressure.

Risk Stratification of Acute Pulmonary Embolism and Determining the Effect on Chronic Cardiopulmonary Complications: The REACH Study.

Introduction Patients with acute pulmonary embolism (PE) are at risk of developing chronic complications including the post-PE syndrome with reduced cardiopulmonary function and chronic thromboembolism pulmonary hypertension (CTEPH). Risk stratification at PE diagnosis is an important tool in predicting early mortality; however, its use in predicting chronic complications has not been evaluated. Objective This study investigates the effect of initial risk stratification of intermediate risk and standard risk PE on the rate of development of chronic complications including right ventricular (RV) dysfunction, residual perfusion defects, and CTEPH. Methods Cases of acute PE ( n = 1,524) were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification discharge diagnosis coding for PE. Evidence of RV dysfunction and systolic blood pressure < 90 mm Hg were used to risk stratify into high, intermediate and standard risk PE. Results There were 508 patients included in the analysis. Intermediate risk PE was associated with higher rates of persistent RV dysfunction as well as residual perfusion defects on repeat imaging. The overall rate of CTEPH was low (0.6%) and there was no difference between the intermediate risk and standard risk PE groups. Conclusion These findings demonstrate that acute intermediate risk PE is associated with higher rates of RV dysfunction on follow-up imaging than standard risk PE. However, the rate of CTEPH was similar between the two groups and overall the CTEPH rate was low among all patients with intermediate and standard risk PE.

Future perspectives in catheter-based treatment of pulmonary embolism.

Pulmonary embolism is the third commonest cause of cardiovascular death globally. The majority of such patients present with low-risk features and can be managed with simple anticoagulation; however, a large group of patients exhibit evidence of right ventricular dysfunction on echocardiography or CT at the time of presentation and these patients are at risk of early haemodynamic compromise, particularly in those with abnormal cardiac biomarkers. Catheter-directed thrombolysis has been proposed as a treatment-strategy for patients with pulmonary embolism with evidence of acute right ventricular dysfunction. We review the current technologies in mainstream use, the evidence base in support of their use and discuss future research requirements in this area.

Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension

Background: The prevalence of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is increasing. We aim to study the role of big endothelin 1 (Big ET1), endothelin 1 (ET1), and neprilysin (NE) in HFpEF with PH. Method: This was a single center prospective cohort study including 90 HFpEF patients; 30 with no PH, 30 with postcapillary PH, and 30 with combined post- and precapillary PH. After enrollment, pulmonary venous and pulmonary arterial samples of Big ET1, ET1, and NE were collected during right heart catheterization. Subjects were then followed long term for adverse outcomes which included echocardiographic evidence of right ventricular dysfunction, heart failure hospitalization, and all-cause mortality. Results: Patients with HFpEF-PH were found to have increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) compared to controls (2.3 ± 1.4 and 1.6 ± 0.9 pg/mL, respectively). ET1W levels were associated with both PH (OR 2.7, 95% CI 1.5–4.7, p = 0.01) and pulmonary vascular resistance (OR 1.6, 95% CI 1.04–2.3, p = 0.03). No evidence of right ventricular dysfunction was observed after 1 year of follow-up. ET1W (OR 1.8, 95% CI 1.2–2.6, p = 0.01) and ET1 gradient (ET1G; OR 1.4, 95% CI 1.04–2, p = 0.03) were predictive of 1-year hospitalization. ET1G ≥0.2 pg/mL was associated with long-term mortality (log-rank 4.8, p = 0.03). Conclusion: In HFpEF patients, ET1W and ET1G are predictive of 1-year heart failure hospitalization, while elevated ET1G levels were found to be associated with long-term mortality in HFpEF. This study highlights the role of ET1 in developing PH in HFpEF patients and also explores the potential of ET1 as a prognostic biomarker.

Oral Milrinone for the Treatment of Right Ventricular Failure in LVAD Patients

Purpose Early and late right ventricular failure (RVF) are major complications during left ventricular assist device (LVAD) support. Therapies to treat RVF are limited, leading to significant morbidity and increased mortality. Intravenous inotropes are a therapy for severe, persistent cases of RVF, but long-term use carries significant risks of infection and thrombosis associated with venous access. CRD-102 is a novel, extended-release form of oral milrinone. The aim of this study is to evaluate the safety of CRD-102 in LVAD patients with chronic RVF. Methods This is a Phase IIa, non-randomized, open-label study of CRD-102. Patients were eligible if they had a durable LVAD for more than 30 days, evidence of right ventricular dysfunction on echocardiogram, an implantable cardioverter defibrillator (ICD) and a right atrial pressure ≥ 12 mmHg. Patients with ongoing ventricular arrhythmias or uncontrolled atrial fibrillation were excluded. Hemodynamics, echocardiographic measures, ICD interrogation and biomarkers were measured before and during a 2-week period of treatment with CRD-102. Results Six patients were enrolled with mean age 64 ± 10 years, 4 male. The average duration of LVAD support was 5.0 ± 2.3 years. At baseline, mean tricuspid annular plane systolic excursion was 9.9 ± 1.3 mm, right atrial pressure was 16 ± 4 mmHg and pulmonary artery pulsatility index was 1.0 ± 0.4. Five patients completed the study and had no ventricular arrhythmias or increased incidence of atrial arrhythmias during the study period (ICD interrogation). One patient stopped study medication after an ICD shock due to ventricular fibrillation while potassium level was 2.8 mmol/L. There were no other adverse events related to therapy. During treatment, cardiac output significantly improved (5.0 ± 1.3 to 6.4 ± 1.7 L/min, p=0.008) while other hemodynamic parameters were unchanged. NT-proBNP numerically improved during the therapy, but did not reach statistical significance (1570 ± 902 to 1068 ± 390 pg/mL, p=0.3). Patient-reported quality of life improved during support. Conclusion Extended-release oral milrinone has an acceptable safety profile. Further studies are warranted to investigate the efficacy of this therapy for chronic RVF in LVAD patients.

Invasive Hemodynamics and Rejection Rates in Patients With Cardiac Sarcoidosis After Heart Transplantation

BackgroundOrthotopic heart transplant (OHT) is increasingly used for end-stage heart failure due to cardiac sarcoidosis (CS). However, concern regarding long-term outcomes in patients with CS after OHT persists because of multiorgan involvement. MethodsBaseline demographics and invasive hemodynamics were measured in 12 patients with CS and 28 patients with nonischemic cardiomyopathy requiring OHT at the time of transplantation, 1 week after OHT, and in routine follow-up. Primary endpoints included changes in pulmonary artery pressure, right ventricular stroke work index, and pulmonary compliance. Secondary endpoints included degree of allograft rejection and death. ResultsDuring a mean follow-up of 73.8 months, no differences in pulmonary artery pressures, right ventricular stroke work index, or cardiac index were observed in patient with CS (n = 12) compared with those without CS (n = 28) between 1 week after OHT and the most recent follow-up. Long-term follow-up showed that pulmonary hemodynamics remained normal in the CS group. International Society for Heart and Lung Transplantation (ISHLT) 1990 grade ≥ 1a rejection occurred less frequently in the CS group (17% vs 68%, P = 0.006), and 0 of 12 patients in the CS group experienced histologic or clinical recurrence of sarcoidosis or ≥2 rejection. Patients with CS had excellent survival after OHT, with 0 deaths or significant rejection. ConclusionsPatients with CS have similar post-transplant hemodynamics as patients without CS, without evidence of right ventricular dysfunction or pulmonary hypertension. Neither significant rejection nor recurrence of sarcoid in the allograft was observed in this cohort of patients with CS. Survival is similar between patients with CS and those without CS. Heart transplant is a viable strategy in selected patients with CS with excellent outcomes.

Does Right Ventricular Dysfunction Predict Mortality in Hemodynamically Stable Patients With Acute Pulmonary Embolism: A Retrospective Review

SESSION TITLE: Venous Thromboembolism SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Acute Pulmonary Embolism (APE) is directly responsible for 100,000 deaths annually. Right ventricular dysfunction (RVD) on admission is considered a poor prognostic factor in these patients though existing evidence of its significance in predicting mortality in hemodynamically stable patients is still unclear. We attempted to clarify this association by doing a retrospective review. METHODS: We retrospectively reviewed electronic medical records of hemodynamically stable patients older than 18 years of age with APE who were admitted to a tertiary care hospital in rural Upstate New York from July 2014 - July 2016. 134 patients were reviewed in two groups: patients who presented with CT or echocardiographic evidence of RVD, and those without RVD. We defined RVD as RV/LV ratio >0.9 or RV hypokinesis on echocardiogram as defined by American Heart association or RV dilation on CT scan. To identify differences in mortality between the two groups, the chi-square/Fisher’s Exact Test and t-tests were used. Similar tests were used to identify univariate associations between RV dysfunction and subject characteristics. All variables with P<0.2 in the initial analysis were included in a stepwise multivariable logistic regression model to predict RV dysfunction. RESULTS: No statistically significant difference was found in 30-day mortality between the groups (7.8% in RV dysfunction and 5.3% in no RVD, P=0.563). The overall prevalence of RV dysfunction was found to be 57% (77/134). Troponin elevation (53.2% in RVD group vs. 19.3 in no RVD group with P<0.01) and central location of thrombus (53.1% vs. 32.1% with P=0.016) were more prevalent in RVD group. A marginally significant difference was found in length of hospital stay among those with RVD versus no RVD (7.13 days vs. 5.46 days p=0.061). The multivariable analysis shows that the odds of RVD were greater for patients with elevated troponin levels (OR =7.8). CONCLUSIONS: There was no difference in 30-day mortality in hemodynamically stable patients with APE having RVD compared to patients with no RVD. Troponin elevation was associated with significantly increased odds of RVD. The findings from this retrospective review do not provide evidence for aggressive management of hemodynamically stable patients with evidence of RVD with fibrinolytics or embolectomy as recommended in some prior studies and physicians may restrict those treatment options to hemodynamically unstable patients with APE. CLINICAL IMPLICATIONS: Aggressive management of hemodynamically stable patients with acute pulmonary embolism having evidence of right ventricular dysfunction with embolectomy or fibrinolytics do not improve mortality and may result in increased complications. Hence one should restrict those treatment options to hemodynamically unstable patients. DISCLOSURE: The following authors have nothing to disclose: Umair Iqbal, Ahmad Chaudhary, Ayesha Jameel, Hafsa Anwar, Edward Bischof No Product/Research Disclosure Information

Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: a post-hoc analysis of the Hokusai-VTE study

In patients with pulmonary embolism, right ventricular dysfunction is associated with early mortality. The Hokusai-VTE study used N-terminal pro-brain natriuretic peptide (NT-proBNP) and right to left ventricular diameter ratio on CT as indicators of right ventricular dysfunction and reported that recurrent venous thromboembolism rates were lower with edoxaban than warfarin. The aim of the current study was to further explore the significance of right ventricular dysfunction and investigate potential explanations for the superiority of edoxaban-ie, differences in baseline clinical characteristics, duration of initial heparin treatment, bleeding rates, or quality of warfarin treatment. The Hokusai-VTE trial was a randomised, double-blind, event-driven non-inferiority trial in patients from centres in 37 countries that compared edoxaban with warfarin in the treatment of acute venous thromboembolism. Patients received treatment for at least 3 months and up to a maximum of 12 months. Patients were followed up for 12 months. Outcome data at 12 months was collected for all patients irrespective of treatment duration. This prespecified subgroup analysis focuses on the included patients with pulmonary embolism. The primary efficacy outcome was the incidence of adjudicated symptomatic recurrent venous thromboembolism defined as a composite of deep vein thrombosis or non-fatal or fatal pulmonary embolism at 12 months. Recurrence rates with edoxaban and warfarin were compared in patients with and without right ventricular dysfunction. In those with NT-proBNP concentrations of 500 pg/mL or higher, we compared baseline characteristics, duration of heparin treatment, and bleeding leading to study drug discontinuation in the edoxaban and warfarin groups. We also assessed quality of warfarin treatment. All analyses were done with the modified intention-to-treat population. The Hokusai-VTE trial is registered with ClinicalTrials.gov, number NCT00986154. Between Jan 28, 2010, and Oct 5, 2012, 8292 patients were enrolled from 439 centres, of whom 8240 received at least one dose of study drug. 3319 patients had pulmonary embolism. NT-proBNP was 500 pg/mL or higher in 465 (30%) of 1565 patients given edoxaban and in 507 (32%) of 1599 given warfarin. Recurrent venous thromboembolism occurred in 14 (3%) of 465 patients in the edoxaban group and 30 (6%) of 507 in the warfarin group (hazard ratio [HR] 0·50, 95% CI 0·26-0·94; p=0·033). The right to left ventricular diameter ratio was 0·9 or higher in 414 (44%) of 937 patients in the edoxaban group and 427 (45%) of 946 in the warfarin group. Recurrent venous thromboembolism occurred in 11 (3%) of 414 and 20 (5%) of 427 patients in the edoxaban and warfarin groups (HR 0·57, 95% CI 0·27-1·17; p=0·13). Baseline characteristics, duration of heparin treatment, and rates of bleeding leading to study drug discontinuation were similar in the edoxaban and warfarin groups and the quality of warfarin management was adequate for patients with NT-proBNP concentrations of 500 pg/mL or higher. Findings from our analysis suggest that edoxaban is more effective than warfarin in the treatment and prevention of recurrent venous thromboembolism in patients with pulmonary embolism and evidence of right ventricular dysfunction. Daiichi Sankyo.

Utility of Inferior Vena Cava Filters in Severe Pulmonary Embolism, Catheter-directed Therapy in Massive and Submassive Pulmonary Embolism, and HAS-BLED Score to Determine Risk of Major Hemorrhage in Pulmonary Embolism.

The American College of Chest Physicians and the American Society of Hematology advocate use of an inferior vena cava (IVC) filter only when anticoagulation is contraindicated, whereas the Society of Interventional Radiology has a list of absolute, relative, and prophylactic indications (2–4). To clarify this issue further, Mismetti and colleagues performed a prospective, randomized, open-label study evaluating the efficacy and safety of retrievable IVC filters for preventing pulmonary embolism (PE) recurrence in patients presenting with acute severe PE and superficial venous thrombosis or deep venous thrombosis (DVT) (1). A total of 399 patients from 17 French centers were openly randomized to either a retrievable IVC filter plus anticoagulation group (n = 200) or an anticoagulation-only group (n = 199). Approximately 65% of patients in each group had evidence of right ventricular dysfunction. Primary outcome was recurrence of fatal or symptomatic nonfatal PE at 3 months. Secondary outcomes were fatal or nonfatal symptomatic PE at 6 months and new or recurrent symptomatic DVT at 3 and 6 months. By 3 months, PE had recurred in six patients in the filter group and three patients in the control group (relative risk with filter, 2.00; 95% confidence interval [CI], 0.51–7.89; P = 0.50). One additional PE recurrence was observed in each group between 3 and 6 months. No difference was observed between the two treatment groups with respect to DVT, major bleeding, or death from any cause at 3 and 6 months. This is a landmark clinical trial as it sheds light on outcomes after IVC filter placement in patients with non–high-risk PE and superficial venous thrombosis or DVT who are also anticoagulated. An earlier study performed by the same investigators determined that in patients with proximal DVT on anticoagulation, IVC filters reduced the risk of PE but increased that of DVT and did not affect survival (5). The strengths of this study are in its originality, the clinical relevance of the subject matter, and the multicenter and prospective nature. A major limitation is that the patient characteristics selected to determine PE severity are not the ones in current use. Standardized criteria for PE severity, such as the Pulmonary Embolism Severity Index score or the classification of patients with acute PE on the basis of early mortality risk proposed by the European Society of Cardiology, were not available while this study was being undertaken (6, 7). Thus, this study may not represent the population that best benefits from an IVC filter placement. An exceptionally high filter retrieval rate seen in this study (79%) will be very difficult to duplicate in the community, leading to increased complications such as DVT, filter migration, and IVC stenosis (8). Another minor limitation was the time (7 yr) needed to complete this study. Studies with inclusion criteria that are better validated to measure PE severity are needed to define the specific role of IVC filters. n