Higher Right Ventricular Systolic Pressure Research Articles

Predictors of long-term outcomes of patients with concomitant moderate aortic and mitral valves diseases: a single tertiary care center experience 2010-2018

Abstract Background To date, moderate concomitant valvular heart diseases have been scarcely studied. This study aimed to further define predictors of long-term outcomes in patients diagnosed with concomitant moderate aortic and mitral valve disease at a tertiary center. Methods In this cohort we included 3257 patients (aged 71.7 ± 12.9 years; 55.2% male; 83.1% white) diagnosed with concomitant moderate aortic and mitral valves diseases who presented to the Cleveland Clinic between 2010 and 2018. The patients’ demographic, clinical and echocardiographic variables were collected. The primary endpoint of the study was the long-term composite outcome defined as heart failure hospitalization or all-cause mortality. We then conducted a univariate and multivariate cox proportional hazard survival analysis for the primary endpoint. Results The patients were followed up for 21.8 months. Baseline demographic characteristics are presented in table 1. Multiple demographic, clinical, and echo variables were evaluated. Using a univariate Cox proportional hazard survival analysis, older Age, history of smoking, Diabetes, Hypertension, Chronic Kidney Disease (CKD), Coronary Artery Disease (CAD), Atrial Fibrillation (Afib), Dyslipidemia, higher Right Ventricular Systolic Pressure (RVSP), higher New York Heart Association (NYHA) class, and lower Left Ventricular Ejection Fraction (LVEF) were associated with worse long-term outcomes. Additionally, patients who underwent an aortic (39.1%) or a mitral valve intervention (29.4%) were associated with better long-term outcomes (HR, 0.710, 0.708; respectively). In comparison, on Multivariable Cox analysis, female sex was significantly associated with worse survival (HR of 1.151, p-value=0.019). However, older Age, history of smoking, Diabetes, CKD, higher RVSP, NYHA class 2, 3, and 4, and lower LVEF remained significantly associated with worse long-term (table 2). Aortic valve intervention remained significantly associated with better survival (HR, 0.861, P-value=0.021). Compared to the Aortic Stenosis/ Mitral Stenosis (AS/MS) group, univariate analysis showed that patients in the Aortic Regurgitation/Mitral Regurgitation (AR/MR), and the AR/MS groups were significantly associated with better long term outcomes (HR, 0.738, HR, 0.575; respectively). Conversely, on Multivariate Cox analysis, AR/MR and AS/MR groups were significantly associated with better survival compared to AS/MS group (HR, 0.580, HR, 0.716; respectively). Conclusion In patients diagnosed with concomitant moderate aortic and mitral valve diseases, female sex, older age, history of smoking, diabetes, CKD, RVSP, NYHA class, LVEF and aortic valve intervention are independent predictors of the composite endpoint of heart failure hospitalization or all-cause mortality.Table 1Table 2

Right Ventricular Dysfunction Patterns among Patients with COVID-19 in the Intensive Care Unit: A Retrospective Cohort Analysis.

Rationale: Right ventricular (RV) dysfunction is common among patients hospitalized with coronavirus disease (COVID-19); however, its epidemiology may depend on the echocardiographic parameters used to define it. Objectives: To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among patients with COVID-19 admitted to the intensive care unit (ICU), as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality. Methods: We conducted a retrospective cohort study of ICU patients with COVID-19 between March 4, 2020, and March 4, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation, respectively, were defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality was assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at the time of transthoracic echocardiogram, and Acute Physiology and Chronic Health Evaluation II score. Results: A total of 116 patients were included, of whom 69% had RV dysfunction by one or more parameters, and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction were the presence of three abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RV fractional area change (24% vs. 36%; P = 0.001), worse RVFWS (16.3% vs. 19.1%; P = 0.005), higher RV systolic pressure (45 mm Hg vs. 31 mm Hg; P = 0.001) but similar TAPSE (13 mm vs. 13 mm; P = 0.30) compared with those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (odds ratio, 2.91; 95% confidence interval, 1.01-9.44), as was the presence of at least two parameter abnormalities. Conclusions: ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

Abstract 14268: Prognostic Value of Clinical and Echocardiographic Factors in Atrial Functional Tricuspid Regurgitation

Introduction: Atrial functional tricuspid regurgitation (AFTR) is an increasingly recognized and prevalent clinical entity associated with adverse outcomes. Hypothesis: We evaluated the clinical and echocardiographic features of AFTR and those associated with poor prognosis. Methods: Consecutive patients with at least moderate-to-severe and isolated AFTR during 14 years were studied, and clinical and echocardiographic parameters including that for TR and the right heart were analyzed. Multivariable and receiver-operative characteristics analyses were performed to identify predictors and their thresholds for all-cause mortality during follow-up. Results: Amongst 155 AFTR patients (age 73±15, female 83%), 58(37%) were symptomatic, and 80 (52%) had atrial fibrillation. There were 77 (49%) deaths over a mean follow-up of 3.9±3.3 years. Multivariable analyses results are shown in the Table 1, were symptoms, right atrial strain and right ventricular systolic pressure (RVSP) were independently associated with mortality during follow-up with hazards ratios (95% confidence intervals, P-values) of 3.27 (1.18-9.04, P=0.022), 0.95 per 1% increase (0.92-0.98, P=0.01), and 1.05 per 1 mmHg increase (1.01-1.09, P=0.003). Area under curve (95% confidence interval) and optimal thresholds for the most important echocardiographic parameters to predict mortality were RVSP 0.80 (0.74-0.92) >44 mmHg, right atrial strain 0.73 (0.62-0.84) < +21%, and right ventricular free wall longitudinal strain 0.69 (0.57-0.81) > -18%. Conclusions: Significant AFTR is associated with adverse prognosis, therefore accurate diagnosis is critical. The key predictors of mortality include symptoms, reduced right atrial strain and higher RVSP, and their presence may prompt more aggressive medical and procedural therapies in AFTR patients that warrants further research.

Abstract 259: BMPR2 +/r899x Mutation Contributes To Sex-linked Disparity In Hypoxia-induced Pulmonary Hypertension

Introduction: Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) and endothelial nitric oxide synthase (eNOS) have been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), a life-threatening disease characterized by pulmonary vascular remodeling, elevated right ventricular systolic pressure (RVSP), and right ventricular hypertrophy (RVH). Although the incidence of this disease is three times higher in females, males with PAH usually have a worse prognosis. The mechanism behind this sex-associated difference remains undetermined. Objective: Determine whether BMPR2 +/R899X loss-of-function mutation contributes to sex-associated differences in PAH, including the degree of vascular remodeling, RVSP, and RVH. Methods: Wild-type (WT) and BMPR2 +/R899X mice (male/female) were exposed to hypoxia (Hx) or normoxia (Nx) for 4 weeks, when the RVSP and RVH were measured. Lung tissue was used for western blot and histological analysis. Results/Discussion: Hx exposure elevated RVSP, inducing RVH in both groups, with a greater effect in BMPR2 +/R899X mice compared to WT (RVSP: 45.0+/- 2.2 and 34.9 +/- 1.3 mmHg, respectively). A higher RVSP was observed in BMPR2 +/R899X female mice, with males exhibiting more pronounced RVH, suggesting females might have a protective mechanism against severe RVH. Lung histology revealed no differences in vessel thickness/area between sexes, which may indicate that the RVSP differences are unlikely a response to vascular remodeling. Hx exposure increased the amount of α-SMA+ microvessels and eNOS expression in BMPR2 +/R899X females compared to males, but further experiments are required to determine whether elevated eNOS reflects higher function or an oxidative stress-driven endothelial cell phenotype. Conclusion: This work is uncovering the translational relevance of BMPR2 +/R899X mutation in the sex-linked differences in PAH incidence, severity, and outcome.

Abstract 10652: Epidemiology and Outcomes of Pulmonary Hypertension in the Cardiac Intensive Care Unit

Introduction: Pulmonary hypertension (PH), defined as an elevated mean pulmonary artery pressure, has been consistently associated with adverse outcomes in hospitalized patients. Limited epidemiologic data exist regarding PH in the cardiac intensive care unit (CICU) population. We used transthoracic echocardiography (TTE) to describe the prevalence, etiology, and outcomes of PH in the CICU. Hypothesis: PH will be associated with higher in-hospital mortality in CICU patients. Methods: CICU patients admitted from 2007 to 2018 who had right ventricular systolic pressure (RVSP) measured via TTE within 1 day of CICU admission were included. PH was defined as an estimated RVSP >35 mmHg. Predictors of in-hospital mortality were determined using multivariable logistic regression. Results: We included 5042 patients with a mean age of 69.4±14.8 (41% females); 81.1% had an admission diagnosis of acute coronary syndrome or heart failure. PH was present in 3085 (61%); the majority (68%) of patients with PH had left heart failure, and 29% had lung disease. In-hospital mortality occurred in 8% and was higher in patients with PH (11% vs. 4%, adjusted OR 1.40, 95% CI 1.03-1.92, p =0.03). PH was associated with higher in-hospital mortality in patients with acute coronary syndrome, heart failure or cardiac arrest (all p <0.01), but not in patients with cardiogenic shock, respiratory failure or sepsis ( Figure ). In-hospital mortality increased as a function of higher RVSP in each admission diagnosis group (adjusted 1.18 per 10 mmHg higher in the entire cohort, 95% CI 1.09-1.28, p <0.001). Conclusions: PH by TTE is very common in the CICU population and remains associated with a higher risk of death during hospitalization even after adjustment. TTE assessment of right heart hemodynamics can predict mortality in CICU patients, with variability across common admission diagnoses. This highlights the importance of PH determined by TTE in hospitalized patients with cardiac critical illness.

Anatomic and Functional Determinants of Atrial Functional Mitral Regurgitation

ABSTRACT Background: It is not well understood why some patients with atrial fibrillation (AF) develop significant atrial functional mitral regurgitation (AFMR). We sought to investigate the mechanistic determinants ofAFMR by comparing anatomic and functional characteristics of patients with AFwho develop significant AFMR (≥2+ MR) to those without AFMR. Methods: We screened AF patients referred for cardiac computed tomography (CCT) before pulmonary vein isolation or appendage occlusion between 2017 and 2019. Patients with primary leaflet pathology, prior mitral surgery, left ventricular dysfunction or dilation, and without echocardiography within six months were excluded. We identified 50 patients with ≥2+ MR, and 50 controls were selected based on age and gender propensity matching. Mitral anatomy was compared by CCT, while diastology and strains were compared by echocardiography. Results: Patients with significant AFMR had larger annular and atrial dimensions (all p < 0.001), insufficient compensatory leaflet growth (p <0.001), shallower posterior leaflet angle (p < 0.001), but similar tenting height and area (p = NS). On strain analysis, they had lower LA strain (p = 0.001) and LV longitudinal strain (p = 0.001), with shorter deceleration time (DT, p = 0.001) and isovolumetric relaxation time (IVRT, p <0.001). Their estimated right ventricular systolic pressure (RVSP) was higher (p = 0.004) with more concomitant significant (≥2+) tricuspid regurgitation (TR, p = 0.006). Conclusions: Patients with significant AFMR have larger atria and annuli with insufficient compensatory leaflet growth but similar tenting height and area with a shallower posterior angle. They also have impaired atrial and ventricular strains and shorter DT and IVRT, with associated higher RVSP and more concomitant TR.

Phenotyping right heart function for prognosticating heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Right heart failure has been shown to portend poor prognosis. The pathophysiology of right heart function is complex, as right ventricular (RV) function is easily affected by preload and afterload. Purpose To test the hypothesis that machine learning would detect heterogeneity in right heart function and improve risk stratifications in a heart failure population Methods This study included 403 heart failure patients who had a history of hospitalization for decompensation. Patients were excluded if they had primary heart valve disease or pericardial disease or a previous cardiac surgery. Hierarchical clustering was undertaken on right heart variables (RV strain, right ventricular systolic pressure (RVSP), vena contracta of tricuspid regurgitation (TR) and diameter of inferior vena cava) to identify homogenous groups of patients with similar profiles of the variables. Cox hazard analysis was used to elucidate the benefit of clustering over each variable for prognosticating heart failure. Endpoint was hospitalization for worsening heart failure. Results Cluster analysis identified three groups with distinct right heart function. Cluster 1 (n = 191) represented patients with preserved RV function and low RVSP (figure A).  On the other hand, cluster 2 (n = 144) had reduced RV function and low RVSP, while cluster 3 (n = 68) had preserved RV function and high RVSP, associated with severe TR and high central venous pressure. The latter 2 clusters carried worse outcome than cluster 1 (p &amp;lt; 0.001, figure B). Cox hazard analysis demonstrated that, although the addition of each right heart variable to baseline model constructed from left heart variables did not improve predictive power, clusters predicted events with a hazard ratio of 1.566, independent from and incremental to the left heart variables (Figure C). Conclusion Cluster analysis identified two distinct phenotypes of right heart failure that were associated with adverse outcomes. This data-driven phenotyping can help in categorizing right heart failure and better prognosticating heart failure. Abstract Figure.

Abstract 14666: Association Between Right Ventricular Systolic Pressure and Health Status Following Transcatheter Aortic Valve Replacement

Introduction: Pulmonary hypertension (PH) was shown in multiple studies to be associated with an increased risk of mortality after transcatheter aortic valve replacement (TAVR). However, it is unclear if echocardiogram derived right ventricular systolic pressure (RVSP) is associated with health status outcomes in surviving patients after TAVR. We explored for an association between baseline RVSP and quality of life in patients before and after undergoing TAVR. Methods: We estimated RVSP by echocardiography using the modified Bernoulli equation in a single-center cohort of patients undergoing TAVR from 2012-2017 . Disease-specific health status was assessed at baseline and 1-month and 12-months after TAVR with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OS). We then explored the association between baseline RVSP and KCCQ-OS before and after TAVR using a linear mixed model with an interaction for time and baseline RVSP and adjusted for baseline mitral valve regurgitation and systolic blood pressure. Results: Among 485 patients who underwent TAVR (mean age 81.7±7.9 years, 54.8% men), baseline RVSP was 42±15 mmHg, and 73% had RVSP &gt;34 mmHg. After TAVR, mean RVSP decreased to 37±13 mmHg at 1 month and 36±14 mmHg at 12 months. Baseline KCCQ-OS was 46±25 and improved to 66.9±23.6 at 1 month and 69.5± 22.6 at 12 months. In the linear mixed model, there was a significant cross-sectional association between baseline RVSP and baseline KCCQ-OS, with higher RVSP associated with worse health status. However, baseline RVSP was not significantly associated with KCCQ-OS at 1 month or 12 months (Figure). Conclusions: RVSP is not associated with worse health status after TAVR. This suggests that while patients with high RVSP are at an increased risk for mortality after TAVR, surviving patients appear to have similar health status as those with normal RVSP.

Abstract 15193: Pulmonary Hypertension in Pregnancy: WHO Group 1 Outcomes Improved, Time to Focus on WHO Group 2

Introduction: Pregnancy is contraindicated in women with pulmonary hypertension (PH), yet many still decide to pursue pregnancy. Hypothesis: We hypothesized improved maternal mortality with PH at our center’s cardio-obstetrics program and sought to identify factors to estimate the risk of major adverse cardiac events (MACE). Methods: Pregnant women with right ventricular systolic pressure (RVSP) ≥35 mmHg or tricuspid regurgitant velocity &gt; 2.8 m/s on transthoracic echocardiogram (TTE) were identified. Women with intermediate to high probability PH by ESC criteria (TTE or catheterization, n = 70) were classified using the 6 th World Society of PH definitions. Results: In 70 women with PH (30 ± 6 years-old, RVSP 52 ± 16 mmHg) there were 12 (17%) with WHO Group 1 PH, 45 (64%) with Group 2 PH, 4 (6%) with Group 3 PH and 9 (13%) with Group 5 PH (Figure A). Baseline characteristics were similar except: Group 1 PH had 83% on prostacyclin (PC) therapy, higher RVSP (78 ± 20 mmHg vs. Groups 2 (46 ± 9), 3 (44 ± 2 mmHg) and 5 PH (48 ± 10mmHg), p&lt;0.01), and compared to Group 2 PH, more Group 1 PH women were diagnosed pre-pregnancy (9 (75%) vs. 12 (27%), p = 0.01) and had cardio-obstetrics care (10 (83%) vs. 16 (36%), p &lt; 0.01) (Figure B - E). There were no peripartum deaths, however 3 (4.3%) women with Group 2 PH had late mortality (7 ± 4 months post-partum). MACE occurred in 24 (34%) women and was more likely in those with: NYHA FC ≥ 2 (95% CI 4.7-57, p &lt; 0.01), pre-eclampsia (95% CI 1.2-13, p = 0.03), RVSP &gt;50 mmHg (95% CI 1.3-10, p = 0.02) and LVEF &lt;50% (95% CI 1.1-8.8, p = 0.04) (Figure F). Preterm birth occurred in 32 (49%) pregnancies, with no neonatal mortality. Conclusion: To conclude, in a large single center cohort we report 100% 1-year survival in Groups 1, 3, and 5 PH, with most Group 1 PH patients on PC therapy and under cardio-obstetrics care. We identify Group 2 PH as an under-recognized group for adverse outcomes in pregnancy, with NYHA FC, pre-eclampsia, RVSP &gt;50 mmHg and LVEF &lt;50% associated with increased MACE.

Ca2+ loading within mitochondria affects arrhythmogenesis in rat right ventricular hypertrophy

Abstract Introduction Delayed afterdepolarizations (DADs) causes triggered arrhythmias, and intracellular Ca2+ (Cai) waves play important roles in the formation of DADs. It remains unclear, however, whether Ca2+ loading within mitochondria affects arrhythmogenesis in right ventricular (RV) hypertrophy. Purpose We focused on the properties of Cai wave propagation, investigating whether changes in Ca2+ loading within mitochondria affects arrhythmogenesis in a rat model of RV hypertrophy. Methods Rats were given a subcutaneous injection of 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). Four weeks after the injection, trabeculae were dissected from RVs. Force was measured using a silicon strain gauge, membrane potential using a microelectrode, Cai using microinjected fura-2 and a CCD camera, and ROS production using 2',7'-dichlorofluorescein (DCF) fluorescence. Cai waves and arrhythmias were induced by electrical stimulation (24°C). To change Ca2+ loading within mitochondria, Ru360 (10 μM), a mitochondrial calcium uptake inhibitor, was added. Results MCT-rats showed lower survival rate (p=0.075), higher RV systolic pressure (48.8±4.6 vs 21.3±6.5 mmHg), and heavier weight ratio of RV free wall to left ventricle (LV) (0.44±0.03 vs 0.25±0.04). MCT-rats showed a wider action potential (APD90, 320±20 vs 205±11 ms), a higher diastolic Cai (177±20 vs 110±8 nM), and faster and larger Cai waves (p&amp;lt;0.01). The velocity and amplitude of Cai waves were correlated with the diastolic Cai in Ctr- and MCT-rats. The velocity of Cai waves in MCT-rats was higher than that in Ctr-rats at the given amplitude of Ca2+ waves (p&amp;lt;0.01). The velocity and amplitude of Cai waves was linearly correlated with the amplitude of DADs in Ctr- and MCT-rats. Ru360 decreased the inducibility of arrhythmias in some trabeculae (MCT-A-rats, n=7), while it did not change it or it inversely increased it in the others (MCT-B-rats, n=11). RV systolic pressure in MCT-A-rats was higher than that in MCT-B-rats (62.2±6.0 vs 41.0±5.2 mmHg), and the weight ratio of RV to LV in MCT-A-rats was higher than that in MCT-B-rats (0.51±0.04 vs 0.41±0.03). The changes in Cai wave propagation velocity after the addition of Ru360 was inversely correlated with the weight ratio of RV to LV (r=−0.64) and the RV pressure (r=−0.60, n=7), suggesting that under the condition of severe RV hypertrophy due to higher RV pressure, reduction of Ca2+ within mitochondria results in a decrease in the velocity of the Cai waves, thereby improving of arrhythmias. In the presence of Ru360, DCF oxidation rate was decreased during 0.5 or 2.5 Hz electrical stimulation (n=5, p&amp;lt;0.05). Conclusions In RV hypertrophy, acceleration of Cai waves occurs due to an increase in diastolic Cai and an increase in Ca2+ sensitivity of the SR Ca2+ release channels, thereby causing arrhythmias. In more severe RV hypertrophy, Ca2+ within mitochondria may also be involved in arrhythmogenesis probably through an increase in ROS production. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science

A RETROSPECTIVE STUDY OF RED CELL DISTRIBUTION WIDTH AND RIGHT VENTRICULAR SYSTOLIC PRESSURE IN PULMONARY HYPERTENSION

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Red Cell Distribution Width (RDW), a measure that reflects the non-homogeneity in sizes of red cells, is a cheap and readily available parameter that has been correlated to various cardiac hemodynamic variables. The 6th World Symposium on Pulmonary Hypertension (PH) recently redefined PH to include all patients with a mean pulmonary artery pressure (mPAP) of greater than 20 mm Hg. Right Ventricular Systolic Pressure (RVSP) on transthoracic echocardiography is usually the first measured parameter when evaluating a patient for PH. We aimed to study the correlation between RDW and RVSP, so as to assess the potential role of RDW as a risk-stratifying aid for PH. METHODS: Patients who underwent right heart catheterization (RHC) at our center between November 2014 and November 2019 were included in this retrospective study. Exclusion criteria included patients under the age of 18, active malignancy, known hemoglobinopathy, blood transfusion within one month of laboratory testing, and lack of RDW measurement within 3 months of the RHC. Hemodynamic parameters obtained on RHC, as were hemoglobin and RDW values from the closest CBC obtained within 3 months of the RHC. Student’s t-test was used to compare RDW between patients with elevated RDW (> 14.5%) and normal RDW (≤ 14.5%). RDW was also compared between various cutoffs of RVSP. RESULTS: 342 patients were included in this study. A significantly higher RVSP was noted in the group with elevated RDW (> 14.5%, n = 130), as opposed to the group with normal RDW (≤ 14.5%, n = 212) (50.57 vs 41.39 mm Hg, p < 0.0001). Mean RDW was compared between high RVSP and non-elevated RSVP groups. When an RVSP > 35 mm Hg was used as the cutoff, there was a significant difference in RDW between the elevated (n = 233) and the normal (n = 109) groups (14.79 vs 13.82%, p < 0.0001). This held true when the cutoff was changed to an RSVP > 20 mm Hg; the elevated RSVP group (n = 336) tended to have a higher RVSP than the normal RVSP group (n = 6) (14.51 vs 12.9%, p = 0.0001). CONCLUSIONS: This study indicates a correlation between RDW and RVSP. This correlation may be a consequence of the association between RDW and mean pulmonary artery pressure (mPAP) in the setting of PH, which has been demonstrated in other previous studies. While the mechanism for this association is unknown, it is hypothesized to be a consequence of the nature of RDW to correlate to the level of inflammatory cytokines; PH is a disease with a significant inflammatory component. Alternatively, RDW may be tied to the level of subclinical hypoxia or hemolysis associated with microvascular disruption in PH. CLINICAL IMPLICATIONS: The measurement of RVSP is usually the first step in the evaluation of a patient with suspected PH. RDW, being a conveniently measured parameter on complete blood counts, appears to correlate with RVSP, and may have a role in pre-test risk stratification for PH. DISCLOSURES: No relevant relationships by Syed Haider, source=Admin input No relevant relationships by Pius Ochieng, source=Web Response No relevant relationships by Divya Ravi, source=Web Response No relevant relationships by NISHANT SHARMA, source=Web Response No relevant relationships by Metlapalli Venkata Sravanthi, source=Web Response No relevant relationships by Pandi Todhe, source=Web Response

The impact of right ventricular dysfunction on the effectiveness of beta-blockers in heart failure with preserved ejection fraction

BackgroundWhether beta-blockers improve the clinical outcomes for heart failure with preserved ejection fraction (HFpEF) characterized by variable cardiac pathophysiology remains controversial. This study aimed to clarify cardiac dysfunction affecting the effectiveness of beta-blockers in patients with HFpEF. MethodsFour hundred and nine patients with HFpEF were enrolled retrospectively, and echocardiography and jugular venous pulse were examined to evaluate their cardiac function. The left ventricular (LV) ejection fraction, mean mitral e′, mean mitral E/e′ ratio, right ventricular (RV) systolic pressure, tricuspid annular plane systolic excursion, and jugular venous pulse waveform were used as indicators of LV contractility, LV relaxation ability, LV filling pressure, RV afterload, RV contractility, and RV diastolic function, respectively. The dominant ‘Y’ descent of the jugular venous waveform was detected as an established hemodynamic sign of a less-distensible right ventricle. ResultsTwo hundred and thirteen patients with HFpEF received beta-blockers. During a mean follow-up period of 33±20 months, 92 patients had cardiovascular events of HFpEF. A less-distensible right ventricle and RV systolic pressure were independent risk factors for cardiovascular events of HFpEF (p=0.016 and p=0.002, respectively). The administration of beta-blockers was not an independent factor, but patients with HFpEF and a distensible right ventricle who received them had fewer events than those who did not (p=0.017). Patients with HFpEF and lower RV systolic pressure (<33mmHg) who received beta-blockers also had fewer events than those who did not (p=0.028). A less-distensible right ventricle or higher RV systolic pressure (≥33mmHg) prevented the beneficial effects of beta-blockers for HFpEF. ConclusionsBeta-blocker usage was not associated with a reduction in the rate of cardiovascular events of HFpEF, but it may have beneficial effects on HFpEF with preserved RV function. RV function may serve as an indicator to administer beta-blockers to patients with HFpEF.

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

BackgroundLiver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases.MethodsFemale Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology.ResultsLiver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group.ConclusionSevere liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

Abnormal Pulmonary Artery Bending Correlates With Increased Right Ventricular Afterload Following the Arterial Switch Operation.

In transposition of great arteries, increased right ventricular (RV) afterload is observed following arterial switch operation (ASO), which is not always related to pulmonary artery (PA) stenosis. We hypothesize that abnormal PA bending from the Lecompte maneuver may affect RV afterload in the absence of stenosis. Thus, we sought to identify novel measurements of three-dimensional cardiac magnetic resonance (CMR) images of the pulmonary arteries and compare with conventional measurements in their ability to predict RV afterload. Conventional measurements and novel measurements of the pulmonary arteries were performed using CMR data from 42 ASO patients and 13 age-matched controls. Novel measurements included bending angle, normalized radius of curvature (Rc), and normalized weighted radius of curvature (Rc-w). Right ventricular systolic pressures (as the surrogate for RV afterload) were measured by either recent echocardiogram or cardiac catheterization. Conventional measurements of proximal PA size correlated with differential pulmonary blood flow (r = 0.49, P = .001), but not with RV peak systolic pressures (r = -0.26, P = .18). In ASO patients, Rc-w correlated with higher RV systolic pressures (r = -0.57, P = .002). Larger neoaortic areas and rightward bending angles correlated with smaller right pulmonary artery Rc (r = -0.48, P = .001; r = 0.41, P = .01, respectively). Finally, both pulmonary arteries had significantly smaller Rc compared to normal controls. Pulmonary arteries exhibit abnormal bends following ASO that correlate with increased RV afterload, independent of PA stenosis. Future work should focus on clinical and hemodynamic contributions of these shape parameters.

Abstract 226: Apoai Mimetic Peptide 6f Prevent Pulmonary Hypertension Induced by Oxidized Lipids

Introduction: Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial occlusion leading to increased pulmonary arterial pressure. Recently, a growing body of evidence demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). Nonetheless, the the causal role of 15HETE in promoting PH development remains elusive. In order to investigate this mechanism, we fed wild type mice with a diet rich in 15HETE and examine whether ApoA-I mimetic peptide can rescue PH induced by 15HETE. Methods: Wild type male mice (C57BL/6) were fed for 3 weeks with regular chow (n=16-21 mice/group), 15HETE (5μg/day), 15HETE diet supplemented with either empty vector or 6F for the last week of 15HETE diet. PH development was assessed every week via serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Results: Echocardiography revealed the first sign of PH as early as one week after starting 15HETE diet and a significant decrease in the pulmonary arterial acceleration time (PAAT) after 2 weeks of treatment (16.6±1.9 vs. 20.6±1.4 msec, p&lt;0.05). At the end of three weeks, mice on 15HETE diet had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05) and RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). This increased pressure was concomitant with a significant increase in pulmonary arteriolar thickness in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). At the end of three weeks mice treated with 6F showed a PAAT similar to control value(19±0.5 msec) concomitant with a significantly lower RVSP than mice fed with 15HETE+empty vector (33.6 ±5.7 vs 40.3±4.6, p&lt;0.05). Conclusion: Our data demonstrates that APOA-I mimetic peptide 6F is able to rescue pre-exisiting PH induced by 15-HETE diet in wild type mice.

Exercising Skeletal Muscle Blood Flow is Diminished in a Rat Model of Pulmonary Arterial Hypertension

PURPOSE: Skeletal muscle dysfunction including a shift toward glycolytic metabolism has been suggested to contribute to exercise intolerance in pulmonary arterial hypertension (PAH) but an exercise perfusion limitation of skeletal muscle has not been identified. Therefore, we performed novel characterization of skeletal muscle blood flow response to exercise in a rat model of PAH. METHODS: Treadmill running at 50% VO2max was performed by male Sprague-Dawley rats (368±13g) injected with monocrotaline (MCT, 60mg/kg) to elicit a severe PAH phenotype (MCT, n=7), or vehicle control (saline) (CON, n=7). Fluorescent microspheres injected during run and rest bouts were utilized to determine blood flow via photo spectroscopy of harvested skeletal muscles. VO2max was measured prior to terminal blood flow studies to characterize exercise capacity of each rat and determine relative exercise intensity for flow analysis. Echocardiographic determination of right ventricular (RV) morphometry and function was also performed. Values are mean ± SE. RESULTS: As expected, MCT exhibited RV hypertrophy (as elevated ratio of RV to LV+S mass, p=0.002, and RV wall thickness in echocardiography, p=0.004), higher RV systolic pressure (p=0.02) and lower VO2max (p=0.03) vs. CON. During exercise, blood flow (expressed as as ml/min per 100g tissue) of the vastus lateralis, semitendinosus, gastrocnemius and biceps femoris was significantly reduced (p=0.02) in MCT (0.187±0.07) compared to CON (0.662±0.17) concomitant with higher (p=0.008) whole blood lactate in MCT (10.44±1.65 mmol/L) vs. CON (4.33±0.72 mmol/L). Further, exercising blood flow was inversely related to blood lactate at exercise (r=-0.603, p=0.03), and positively related to cardiac output (r=0.61, p<0.05). At rest, there was a tendency for both blood flow reduction (p=0.06) and higher lactates (p=0.09) in MCT (0.053±0.01, 5.98±2.48 mmol/L) vs. CON (0.148±0.04, 1.82±0.19 mmol/L). CONCLUSIONS: Exercising blood flow is reduced in a rat model of PAH and may contribute to metabolic limits to exercise capacity. Future studies will explore ways to augment skeletal muscle exercising blood flow in PAH, with the hope of improving tolerance for exercise in patients. Funding: NIH-NHLBI R-15 (MB Brown)

Abstract 250: Pulmonary Hypertension Induced by 15-HETE is Reverse by Apoai Mimetic Peptide 6f Administration

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial occlusion leading to increased pulmonary arterial pressure. Recently, a growing body of evidence demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). Recently, our group demonstrated that 15HETE induce PH. Nonetheless, the precise mechanism by which 15HETE participates in PH development remains elusive. In order to investigate this mechanism, we fed wild type mice with a diet rich in 15HETE and examine whether ApoA-I mimetic peptide can rescue PH induced by 15HETE. Methods: Wild type male mice (C57BL/6) were fed for 3 weeks for 3 weeks with regular chow (n=16-21 mice/group), 15HETE (5μg/day), 15HETE diet supplemented with either empty vector or 6F for the last week of 15HETE diet. PH development was assessed every week via serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Results: Echocardiography revealed the first sign of PH as early as one week after starting 15HETE diet and a significant decrease in the pulmonary arterial acceleration time (PAAT) after 2 weeks of treatment (16.6±1.9 vs. 20.6±1.4 msec, p&lt;0.05). At the end of three weeks, mice on 15HETE diet had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05) and RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). This increased pressure was concomitant with a significant increase in pulmonary arteriolar thickness in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). Furthermore, these WT mice did not develop atherosclerosis as there was no detectable plaque in aorta of the mice on 15HETE diet. At the end of three weeks mice treated with 6F showed a PAAT similar to control value(19±0.5 msec) concomitant with a significantly lower RVSP than mice fed with 15HETE +empty vector (33.6 ±5.7 vs 40.3±4.6, p&lt;0.05). Conclusion: Our data demonstrates that APOA-I mimetic peptide 6F is able to rescue pre-exisiting PH induced by 15-HETE diet in wild type mice.

Acute Cardiac Effects of Severe Pre-Eclampsia

BackgroundPre-eclampsia with severe features (PEC) is a pregnancy-specific syndrome characterized by severe hypertension and end-organ dysfunction, and is associated with short-term adverse cardiovascular events, including heart failure, pulmonary edema, and stroke. ObjectivesThe authors aimed to characterize the short-term echocardiographic, clinical, and laboratory changes in women with PEC, focusing on right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle tracking parameters. MethodsIn this prospective observational study, the authors recruited 63 women with PEC and 36 pregnant control patients. ResultsThe PEC cohort had higher RVSP (31.0 ± 7.9 mm Hg vs. 22.5 ± 6.1 mm Hg; p < 0.001) and decreased global RV longitudinal systolic strain (RVLSS) (−19.6 ± 3.2% vs. −23.8 ± 2.9% [p < 0.0001]) when compared with the control cohort. For left-sided cardiac parameters, there were differences (p < 0.001) in mitral septal e′ velocity (9.6 ± 2.4 cm/s vs. 11.6 ± 1.9 cm/s), septal E/e′ ratio (10.8 ± 2.8 vs. 7.4 ± 1.6), left atrial area size (20.1 ± 3.8 cm2 vs. 17.3 ± 2.9 cm2), and posterior and septal wall thickness (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). Eight women (12.7%) with PEC had grade II diastolic dysfunction, and 6 women (9.5%) had peripartum pulmonary edema. ConclusionsWomen with PEC have higher RVSP, higher rates of abnormal diastolic function, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema, when compared with healthy pregnant women.

Impact of right ventricular distensibility on congestive heart failure with preserved left ventricular ejection fraction in the elderly.

To elucidate involvement of age-related impairments of right ventricular (RV) distensibility in the elderly congestive heart failure (CHF), we examined the prevalence of less-distensible right ventricle in patients with preserved left ventricular ejection fraction (LVEF) over a wide range of ages. In 893 patients aged from 40 to 102years, we simultaneously recorded electrocardiogram, phonocardiogram, and jugular venous pulse wave. Using signal-processing techniques, the prominent 'Y' descent of jugular pulse waveform was detected as a hemodynamic sign of a less-distensible right ventricle. Prevalence of less-distensible right ventricle and elevated RV systolic pressure increased along with aging from the 50s to the 90s in an exponential fashion from 3.3 and 12% up to 33 and 61%, respectively (p<0.001 for each). This age-dependent deterioration of ventricular distensibility was not observed for the left ventricle. Higher age and higher RV systolic pressure were independently associated with less-distensible right ventricle (Odds ratio, 1.05 per 1year, p=0.003; and 1.03 per 1mmHg, p=0.026, respectively). The elderly CHF was associated with high prevalence of the less-distensible right ventricle and higher RV systolic pressure, both of which were independent risk factors for CHF (Odds ratio, 5.27, p=0.001, and 1.08 per 1mmHg, p<0.001, respectively). In elderly patients with preserved LVEF, the combination of a less-distensible right ventricle and a high RV systolic pressure seems to be related to developing CHF. The less-distensible right ventricle and elevated RV systolic pressure are closely associated with CHF with preserved LVEF in the elderly patients.

Abstract 216: Causal Role of Oxidized Lipids in Pulmonary Hypertension Development

Pulmonary arterial hypertension (PAH) is a deadly disease characterized by increased pulmonary arterial pressure and pulmonary vascular occlusion. Recently, we and others demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15-HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). We hypothesized that diets rich in 15-HETE are sufficient to cause PH in wild type mice. We also examined whether 15-HETE or its metabolites are required to cause PH by comparing the effect of 15-HETE with 15-HETE methyl ester, which is a stable form of 15HETE that is not easily metabolized. C57BL/6 male mice were fed for 3 weeks with 15-HETE diet (5μg/day), 15-HETE methyl ester (15-HETE-ME, 5μg/day), or regular chow diet (n=8-21 mice/group). PH development was followed via weekly serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via direct heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Echocardiography revealed the first sign of PH in mice on 15HETE diet as early as one week and a significant decrease in the pulmonary arterial acceleration time after 2 weeks of treatment (16.6±1.9 vs. 21.2±1.4 msec, p&lt;0.05). Mice on 15HETE diet also had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05). Increase in RVSP was concomitant with significantly higher RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). Pulmonary arteriolar thickness was also significantly increased in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). Our new model of PH is not a model of atherosclerosis as there was no detectable plaque in aorta of the mice on 15-HETE diet. Finally, mice on 15-HETE-ME diet also developed PH as RVSP was significantly higher compared to control (31.3±1.1 vs. 39±3 mmHg, p&lt;0.05). The severity of PH was similar in 15HETE-ME and 15HETE, confirming 15HETE itself and not its metabolites is sufficient to cause PH in wild type mice. We have developed a new and physiologically relevant animal model to study PH as a consequence of oxidized lipids overload as it occurs in humans with PAH.