Preserved Right Ventricular Function Research Articles

Right ventricular dysfunction after coronary artery bypass grafting

Abstract Background Impaired right ventricular (RV) function is a frequent echocardiographic finding following coronary artery bypass grafting (CABG). It is subject of debate whether this finding reflects actual RV dysfunction with clinical impact, or rather limitations of the applied echocardiographic measurements. Purpose We aimed to investigate prevalence of RV dysfunction using currently available echocardiographic measurements, and self-reported physical capacity more than two years after CABG. Materials and methods This pre-specified cross-sectional substudy of the SWEDEGRAFT trial included patients scheduled for follow-up more than two years after elective CABG at our institution. The SWEDEGRAFT trial is an ongoing multicenter, randomized clinical trial comparing patency of saphenous vein grafts harvested with "no-touch" and open skeletonized technique. We prospectively assessed RV function with multivariable transthoracic echocardiography. Self-reported physical capacity was assessed using the three items for physical limitation of the Seattle Angina Questionnaire (SAQ-7) (3 denotes the worst and 15 the best possible physical capacity), as well as NYHA-class. Baseline and procedural data were retrieved from the SWEDEGRAFT trial. Preoperative echocardiographies were systematically reexamined. Results We enrolled 207 patients into our substudy at a median follow-up after CABG of 31.0 (range 24.2-39.9) months. RV function assessed by tricuspid annular plane systolic excursion (TAPSE) was significantly reduced compared to the preoperative assessment. In contrast, postoperative RV function as assessed by RV fractional area change (FAC) was preserved. Similarly, assessment of three-dimensional RV ejection fraction (3D-RVEF) indicated preserved RV function (mean 49.4 ± 6.3 %). Mean RV global longitudinal strain was -19.7 (±3.6), and mean RV free wall strain was -22.7 (±4.9). At follow-up, assessments of 3D-RVEF and strain modalities were obtainable in 51.7% and 72.4% of patients, respectively. Patient-reported functional capacity was excellent (median score 15, interquartile range 1.5). NYHA-class improved significantly (NYHA-class I preoperative 49.4% vs. postoperative 61.4%, p=0.032). Postoperative median pro-Brain Natiuretic Peptide levels were 163 (interquartile range 195) ng/L. Conclusion RV systolic function was preserved more than two years after CABG when assessed by RV FAC and 3D-RVEF despite significant reduction in TAPSE. These findings likely reflect the increased sphericity of the RV following opening the pericardium during surgery. Our study supports that measurements of longitudinal systolic parameters likely underestimate RV systolic function after CABG.

Abstract 14585: Early Right Ventricular Snail Expression is a Druggable Target to Improve Right Ventricular Function in Pressure-Overloaded Right Heart Failure

Introduction: Cardiac fibrosis disrupts the myocardial architecture, impairs the exchange of oxygen and nutrients, and puts the heart at risk of failure. Snail (SNAI1) is a transcriptional factor involved in cell plasticity that has been linked to fibroblast-to-myofibroblast transition (FMT) in the hypoxic heart, however, it is unknown whether inhibition of FMT reduces fibrosis and improves right ventricular (RV) function in the pressure overloaded RV. We hypothesized that Snail is necessary for FMT and, as BMP signaling inhibits Snail, that two BMPR2 activators, FK506 and Enzastaurin, reduce cardiac fibrosis and improve cardiac function in a pulmonary artery banding (PAB) mouse model. Methods and Results: We performed PAB surgery on snail-YFP reporter mice and observed transient Snail expression exclusively in the RV 3-7 days after inducing pressure overload (Fig. 1). In PeriostinCre-TdTomato reporter mice we showed that Snail was expressed in proliferating Periostin and vimentin positive fibroblasts representing activated myofibroblasts. In vitro , stimulation of cardiac fibroblasts with TGFbeta resulted in the early expression of Snail at 2 hours, followed by a Snail-dependent Acta2 expression after 24 hours and Col1 after 48 hours, suggesting the critical role of Snail in fibroblast activation. Furthermore, application of stretch and pressure (50kPa) to cardiac fibroblasts, mimicking pressure-overload in vivo , increased Snail expression. FK506 and Enzastaurin inhibited Tgf-b induced Snail expression in vitro as well as in vivo when administered immediately after PAB surgery (Fig. 2). Finally, long-term treatment with Enzastaurin resulted in preserved RV function at week 7 as assessed by cardiac MRI (Fig. 3, N=6). Conclusions: Snail expression is strongly associated with fibroblast activation in the pressure-overloaded RV. Inhibiting Snail with BMPR2 pathway modulators is a promising approach to improve RV function in the pressure-overloaded RV.

Right-Left Ventricular Interdependence in Repaired Tetralogy of Fallot Patients With Right Ventricular Heart Failure.

Patients with repaired tetralogy of Fallot (rTOF) continue to face a heightened risk of deteriorating cardiac function, and quantitative techniques of cardiac MRI-derived cardiac structure and function provide an opportunity to explore the causes and mechanisms of cardiac deterioration. To explore right-left ventricular interdependence in rTOF patients before and after the onset of right ventricular (RV) heart failure. Retrospective. One hundred eighteen rTOF patients (21.85 [16.74, 29.20] years, 58 females) and 34 controls (23.5 [21, 26.5] years, 17 females) that underwent cardiac MRI were analyzed, with rTOF patients being further subdivided into those with preserved RV function (N = 54) and those that experienced RV heart failure (N = 64). 3.0 T/balanced steady-state free precession sequence. RV, left ventricular (LV), and septal strain; RV and LV volume. Chi-squared tests or Fisher's exact test, One-way ANOVAs with Bonferroni's post hoc test, Pearson/Spearman correlation, and multivariate backward linear regression analysis. A two-tailed P < 0.05 was deemed as the significance threshold. The MRI-derived RV, LV, and septal strain decreased sequentially in controls, patients with preserved RV function, and patients with RV heart failure, with a good intra-observer (0.909-0.964) and inter-observer (0.879-0.937) agreement. Correlations between LV and RV strain were found to change sequentially with RV function and were the closest in rTOF patients with RV heart failure (r = -0.270 to 0.506). Correlations between RV volume and septal strain was variable in controls (r = 0.483 to -0.604), patients with preserved RV function (r = -0.034 to -0.295), and patients with RV heart failure (r = -0.026 to 0.500). Multivariate analyses revealed that the RV longitudinal strain was independently correlated with LV strain in three directions in rTOF patients with RV heart failure (Radial -0.70 [-1.33, -0.06]; Circumferential 0.44 [0.17, 0.72]; Longitudinal 0.54 [0.26, 0.81]). In rTOF patients, the coupling between RV volume and septal strain was broken during RV function compensation, and the adverse effect of RV on LV deformation was highest in patients with RV heart failure. 4 TECHNICAL EFFICACY: Stage 5.

Right ventricular global dysfunction score: a new concept of right ventricular function assessment in patients with heart failure with reduced ejection fraction (HFrEF).

Right ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size. A total of 836 stable patients with HFrEF (LVEF 23.6 ± 5.8%, 82.8% males, 68% NYHA III/IV) underwent echocardiographic evaluation and were prospectively followed for a median of 3.07 (IQRs 1.11; 4.89) years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support. RV size (measured as RV-basal diameter, RVD1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area (RVD1i, p < 0.05 compared to non-indexed value). A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction (1-4 for preserved RV function, mild, moderate and severe dysfunction, respectively). RVGDs showed a superior prognostic role compared to RV dysfunction grade alone (ΔAUC >0.03, p < 0.0001). In every subgroup of RVGDs (<20, 20-40, 40-60, >60), patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size (all p > 0.50), independent of tricuspid regurgitation severity and degree of pulmonary hypertension. RV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function.

Left atrial dynamics and the pulmonary circulatory-right ventricular uncoupling in patients with severe degenerative mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background The uncoupling of right ventricular (RV) function to pulmonary circulation (Pc) represents a prognostic index in patients affected by degenerative mitral regurgitation (DMR) undergoing surgical or percutaneous repair. In this context, the deterioration of Left Atrial (LA) dynamics favors the development of pulmonary venous congestion and vascular remodeling, triggering pulmonary hypertension (PH) and right ventricular (RV) dysfunction. However, the relationship between LA function and RV-to-Pc coupling is not well defined in this population. Purpose The aim of the study was to investigate the association between RV-to-Pc uncoupling, assessed by the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPS), and LA dynamics, evaluated with Speckle Tracking Echocardiography (STE), in patients with DMR. Methods 351 consecutive patients with hemodynamically-significant DMR who were evaluated for cardiac surgery at San Raffaele Hospital and underwent a complete transthoracic and transesophageal echocardiography were retrospectively enrolled (mean age 59±14 years, 65% males). Patients were then stratified in two groups according to TAPSE/PAPS ratio (group I: TAPSE/PAPS &amp;gt;0.4 mm/mmHg; group II: TAPSE/PAPS ≤0.4 mm/mmHg). LA function was evaluated analyzing LA strain at peak relaxation (Global peak atrial longitudinal strain) and STE analysis was performed offline. All the patients enrolled were in sinus rhythm. Results At baseline, patients exhibited normal LV dimensions and function (EDVi 70±20 ml/m2, LVEF 63±6%), increased LA size (48±20 ml/m2) and a mean GPALS of 26±13%. Additionally, a preserved RV function and coupling with PC was found in the population in study (average TAPSE/PASP at admission: 0.84±0.2 mm/mmHg), with only 10% of the cohort exhibiting a reduced TAPSE/PAPS ratio. When stratified according to RV-to-PC coupling, patients with higher TAPSE/PAPS (&amp;gt;0.4 mm/mmHg) exhibited significantly higher values of LA reservoir strain (group I: GPALS 27.8±12.7% vs group II GPALS 22.7±11.3%; p = 0.04) (Figure 1, 2). Additionally, a direct correlation between LA-Strain values and TAPSE/PAPS ratio was noticed (r=0.3, CI 95% 0.21–0.5; p&amp;lt;0.001). Conclusions In DMR, there is a strong association between echo-derived measures of LA mechanics and RV to Pc uncoupling, with higher values of LA strain correlating with a better RV functioning and coupling. These results, although preliminary, suggest the importance of a multiparametric approach in the risk-stratification of these patients, potentially improving the long-term outcome.

Results after Tricuspid Valve Surgery for Preserved and Dysfunctional Right Ventricle.

This study aimed to compare long-term outcomes after tricuspid valve (TV) repair (TVr) with those after TV replacement (TVR) by adjusting the right ventricular (RV) volume and function. We enrolled 147 patients who underwent TVr (n = 78) and TVR (n = 69) for grade 3 or 4 tricuspid regurgitation and had preoperative cardiac magnetic resonance data. Long-term clinical outcomes were compared between the two groups using inverse probability treatment weighting (IPTW) to adjust for differences in preoperative characteristics between the two groups. Subgroup analyses were performed in patients with preserved and dysfunctional RV (ejection fraction < 50%). There were no significant differences in operative mortality or postoperative complications between the two groups before and after the IPTW adjustment. Five- and 10-year overall survival rates were 84.2 and 67.1%, respectively. Five- and 10-year cumulative incidences of TV-related events (TVREs) were 33.1 and 55.6%, respectively. There were no significant differences in overall survival and cumulative incidence of TVREs after IPTW adjustment (p = 0.236 and p = 0.989, respectively). The risk-adjusted overall survival was marginally higher in the TVr group of patients with preserved RV function (p = 0.054), while no such significant difference was found between the two groups of patients with dysfunctional RV (p = 0.513). Adjusted long-term clinical outcomes after TVr and TVR were comparable. TVr might be beneficial for patients with preserved RV function in terms of long-term survival; however, this benefit might disappear in patients with RV dysfunction.

Preservation of Right Ventricular Function in Middle-Aged Recreational Endurance Athletes

Preservation of Right Ventricular Function in Middle-Aged Recreational Endurance Athletes

Effects of radiofrequency catheter ablation for premature ventricular complexes originating from the right ventricular outflow tract on right ventricular function.

This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p < .001). FAC and GLS were significantly worse in proportion to PVC burden (p < .001 and p < .001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052-1.134); p < .001]. Improvement in FAC (13.0 ± 8.7% and -2.5 ± 5.6%, respectively; p < .001) and GLS (-6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p < .001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA.

Right Ventricular Maladaptation to Pressure Overload in Fischer Rats Is Associated With Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics.

We explored the mechanism of maladaptive right ventricular (RV) remodeling in Fischer compared with Sprague-Dawley (SD) rats exposed to pressure overload. Pulmonary hypertension was induced by injection of the VEGFR antagonist, SU5416, followed by a 3-week exposure to hypoxia (Sugen chronic hypoxia). In vivo oxidative metabolism was assessed by RV/left ventricle ratio of [11C]acetate positron emission tomography clearance (kmono). Unbiased, global transcriptional and proteomic profiling was performed in Fischer and SD rats at baseline and after Sugen chronic hypoxia. All Fischer rats succumbed to RV failure by 5 weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (P<0.0001). Fischer rats exhibited increased oxidative metabolism at 4 weeks (P<0.05) and impaired RV efficiency compared with SD (work metabolic index: 52±10 versus 91±27 mmHg·mL/cm2, respectively; P<0.05), but no differences in mitochondrial complex activity. AK1 (adenylate kinase 1) was among the top 10 differentially expressed genes between Fischer and SD rats, with markedly lower RV expression in Fischer rats (FC: 3.36, P<0.05), confirmed by proteomic analysis and validated by Western blotting (>10-fold reduction, P<0.001). While whole-genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region likely involved in the regulation of AK1 expression. Therefore, Fischer rats exhibit profound AK1 deficiency and inefficient cardiac energetics likely related to reduced adenosine triphosphate shuttling from the mitochondria to the contractile fibers. This represents a novel mechanism for RV failure in response to chronic increases in afterload.

Abstract P3070: Distinct Inflammatory Milieu In Patients With Right Heart Failure

Introduction: Right heart failure (RHF) is associated with worse clinical outcomes in patients with heart failure (HF) and pulmonary hypertension. Previous studies have shown elevated circulating proinflammatory cytokines in patients with HF; however, no study has compared the inflammatory signature in patients with RHF to those with HF and preserved right ventricular (RV) function. Hypothesis: We predicted that patients with RHF would have a distinct inflammatory milieu compared to normal and HF patients. Methods: We recruited adult patients undergoing right heart catheterization (RHC) and excluded those with a history of transplant, autoimmune disease, malignancy, or infection. Patients underwent blood sampling during RHC and were classified into normal, HF, and RHF cohorts a priori . We then performed multiplex protein assay on serum targeting cytokines, chemokines, and growth factors. Results: A total of 43 patients were included. HF and RHF patients had similar demographics and cardiac indices, but the RHF cohort had elevated markers of congestion characterized by higher right atrial pressure and creatinine, and a trend towards higher bilirubin (Figure). Patients with RHF had elevated levels of select proinflammatory cytokines, chemokines, and growth factors. Of the factors measured, VEGF-A, soluble CD163, and CXCL12 were predictive of all-cause mortality and LVAD/transplant-free survival. Conclusion: Patients with RHF have a distinct proinflammatory signature compared to those with preserved RV function. VEGF-A, soluble CD163, and CXCL12 predicted clinical outcomes in an advanced HF population.

Prognostic impact of right ventricular function affected by pulmonary hypertension in hospitalized heart failure patients

BackgroundPulmonary hypertension (PH) may affect right ventricular (RV) function; however, the prognostic implications of RV function in patients with heart failure and PH remain unclear. We aimed to investigate the impact of RV function on the prognosis of hospitalized heart failure patients with and without PH. MethodsThis observational study initially included 1,349 consecutive hospitalized heart failure patients. After excluding patients who died in hospital, whose left ventricular (LV) function was preserved, and whose echocardiography data were incomplete, 573 patients with heart failure and reduced LV ejection fractions (HFrEF) were analyzed. The patients were grouped according to RV dysfunction that was defined as an RV-tissue Doppler imaging systolic velocity (RV-TDI s’) of ≤9.5 cm/s. The primary endpoint was a composite of cardiovascular death and rehospitalization as a consequence of heart failure. ResultsOverall, the patients with reduced RV function had significantly higher event rates than those with preserved RV function (log-rank test p = 0.01). This prognostic impact was observed in the patients with PH (p = 0.001) and was not evident among the patients without PH (p = 0.39). In the patients with PH, reduced RV function independently predicted the prognosis after adjusting for the covariates (adjusted hazard ratio: 3.12; 95% confidence interval: 1.44 to 6.73). ConclusionRV dysfunction that was estimated during hospitalization using the RV-TDI s’, which is a simply determined index, may predict clinical outcomes in hospitalized patients with HFrEF and PH after discharge, but not in those without PH.

Pathophysiological role of right ventricular function and interventricular functional mismatch in the development of pulmonary edema in acute heart failure

BackgroundParameters of cardiac function related to the development of pulmonary edema (PE) in acute heart failure (AHF), including right ventricular (RV) function and a mismatch of interventricular function, are not fully elucidated. The aim of this study was to verify the hypothesis that a relatively preserved RV function compared with left ventricular function may be associated with the development of PE by using two-dimensional speckle tracking echocardiography (2DSTE). MethodsHospitalized patients with AHF at 11 institutions were enrolled. PE was defined as lung congestion on chest X-ray with hypoxemia. Patients with systolic blood pressure ≥140 mmHg on admission were defined to have hypertensive AHF. Echocardiographic analyses, including 2DSTE, were performed prior to discharge. The index of mismatch between RV and left ventricular systolic function was assessed by interventricular longitudinal strain difference (IVLSD) which was defined as RV free wall longitudinal strain and left ventricular global longitudinal strain. ResultsOf 610 patients with AHF, 422 (69.2%) had PE. In patients with PE, IVLSD (p = 0.007) and RV fractional area change ratio (p<0.001) was significantly higher than those in patients without PE. In patients with non-hypertensive AHF, RV fractional area change ratio, age, ischemic etiology, and serum brain natriuretic peptide (BNP) levels were independent predictors of PE. In patients with hypertensive AHF, IVLSD, age, and serum BNP levels were independent predictors of PE. ConclusionsPreserved RV function might be one of the underlying mechanisms of the development of PE in AHF. Furthermore, interventricular functional mismatch might be related to the development of PE in hypertensive AHF.

Longitudinal change in postoperative right ventricular systolic function in patients undergoing surgery for isolated tricuspid regurgitation

Right ventricular (RV) dysfunction is an indication for tricuspid valve (TV) surgery in patients with severe isolated tricuspid regurgitation (TR). Postoperative RV dysfunction is associated with poor outcome; however, the longitudinal changes in RV function before and after surgery have not been established. We retrospectively analyzed 24 patients who underwent TV surgery for isolated severe TR. For assessing RV systolic function, we measured the RV fractional area change (RVFAC) at baseline, and 1 (immediate) and 4–20 (late) months after surgery. We divided patients into 2 groups according to the RVFAC late after surgery (<35%, post-op. reduced; and ≥35%, post-op. preserved). The mean RVFAC was significantly decreased immediately after surgery compared to baseline (41.5 ± 10.1% vs. 32.2 ± 9.6%; p < 0.001). The RVFAC reduction was still observed late after surgery (35.5 ± 7.4%; p = 0.002). Of 24 patients, 12 patients (50%) had preserved RV systolic function late after surgery. Although there was no significant difference in the preoperative RVFAC between the 2 groups, the preoperative RV end-systolic area (RVESA) /body surface area (BSA) was significantly less in the post-op. preserved RV systolic function group (13.8 ± 4.3 cm2/m2 vs. 8.6 ± 2.6 cm2/m2; p = 0.001). The optimal cut-off value for the preoperative RVESA/BSA in detecting postoperative preserved RV systolic function was 10.8 cm2/m2 (AUC, 0.85; sensitivity, 91.7%; and specificity, 75.0%). In patients undergoing surgery for isolated severe TR, the RVFAC was significantly decreased immediately after surgery and the reduction continued late after surgery. The preoperative RVESA/BSA might be helpful to predict preserved RV function after surgery.

Abstract 11091: Failure of Right Ventricular Adaptation to Pressure Overload Due to a Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics

Introduction: Interindividual heterogeneity in the ability of the right ventricular (RV) to adapt to pressure overload in pulmonary hypertension (PH) is likely influenced by genetic determinants. We took advantage of strain-dependent, maladaptive RV remodeling in Fischer compared to Sprague-Dawley (SD) rats to define the molecular and genetic mechanisms that predispose to development of RV failure in PH. Methods/Results: In the SU5416/hypoxia(SUHx) PH model, Fischer rats exhibited RV failure and 100% mortality by 5-weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (p&lt;0.0001). In vivo oxidative metabolism, assessed by [ 11 C]acetate PET, was increased in Fischer rats at 4 weeks (p&lt;0.05), associated with impaired RV efficiency compared to SD (work metabolic index: 58±12 vs 102±20 mmHg·mL/cm 2 , respectively; p&lt;0.001), but no differences were observed in mitochondrial complex activity in permeabilized RV cardiac fibers. Adenylate Kinase 1 (AK1) was among the top ten differentially expressed genes between Fischer and SD rats by unbiased transcriptomic analysis, with markedly lower expression in the RV of Fischer rats (FC:3.36, P&lt;0.05). Profound AK1 deficiency was confirmed by proteomics and validated by Western blotting (&gt;10-fold reduction, P&lt;0.001). Fischer rats also exhibited evidence of hemolysis, recapitulating the hemolytic phenotype seen in patients with rare AK1 coding region mutations. While whole genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region. AK1 levels were also reduced in the RV of PH patients with decompensated RV function and right heart failure. Conclusion: Fischer rats with AK1 deficiency have inefficient energetics likely related to reduced ATP shuttling from the mitochondria to the contractile fibers, which represents a novel mechanism for RV failure in response to chronic increases in afterload.

Changes of Right Ventricular Function After Transcatheter Aortic Valve Replacement and Association With Outcomes

BackgroundBaseline right ventricular (RV) dysfunction represents a predictor for poor outcome in patients undergoing transcatheter aortic valve replacement (TAVR). However, RV function may improve after TAVR, which could have important implications on outcomes. The aim of the present study was to assess changes in RV function after TAVR and its prognostic value regarding clinical outcome. Methods and ResultsPatients undergoing TAVR at our institution were consecutively enrolled and categorized into 4 groups according to changes in RV function during echocardiographic follow-up at 6 months. A total of 188 patients were included. Of those showing normal function at baseline, 87% (130/149) had preserved RV function at follow-up (group 1), whereas 13% (19/149) developed new RV dysfunction (group 2). Of those with RV dysfunction at baseline (39 patients), RV function normalized in 46% (18/39) (group 3) and remained impaired in 54% (21/39) (group 4). The Kaplan–Meier estimated survival at 3 years was highest in patients in group 1 (83%), intermediate in group 2 (65%) and 3 (69%), whereas group 4 had the worst survival (37%; P < .001). Furthermore, new or persistent RV dysfunction was identified to be independently associated with mortality during follow-up (hazard ratio 2.55; interquartile range 1.03–6.47, P = .004). ConclusionsPatients with preserved RV function have a high 3-year survival. Normalization of RV function showed improved survival compared with patients with persistent RV dysfunction, who had a dismal prognosis despite TAVR.

CA125 Predicts Right Heart Hemodynamic and Function and Identifies Distinct Congestion Phenotypes: Guidance for Therapy

<h3>Purpose</h3> Elevated carbohydrate antigen 125 (CA125) correlates with serosal effusions and has previously been thought to be associated with the clinical severity of heart failure (HF) and fluid congestion. We assessed CA125 as a predictor of hemodynamics and investigated the additive prognostic benefit of B-type natriuretic peptide (BNP). <h3>Methods</h3> Between 2015-2019, 235 patients hospitalized for HF were prospectively assessed for CA125 and BNP serum levels simultaneously with echocardiography and right heart study. <h3>Results</h3> CA125 correlated positively with intracardiac pressures and inversely with cardiac index (CI). The strongest correlation was for right atrial pressure (RAP) (ρ = 0.82, p<0.001). CA125 >42 U/mL had a sensitivity of 95.8% and specificity of 95.3% for the prediction of RAP ≥11 mmHg. The predictive accuracy of CA125 vs BNP was superior for RAP (AUC 0.99 vs 0.84, p<0.001) and right ventricular (RV) pressure (AUC 0.99 vs 0.82, p<0.001), but BNP was better for the prediction of pulmonary capillary wedge pressure (AUC 0.95 vs 0.82, p<0.001) and CI (AUC 0.92 vs 0.84, p=0.03). Elevated CA125 was independently associated with increased right heart pressures, while BNP with left-sided filling pressures and lower CI (p<0.05). Combining CA125 and BNP values delineated 4 distinct HF congestion phenotypes (Figure): high CA125-high BNP - reduced ejection fraction (HFrEF) with RV dysfunction; low CA125-high BNP - HFrEF with preserved RV function; and high CA125-low BNP and low CA125-low BNP - preserved EF, with and without RV dysfunction, respectively. <h3>Conclusion</h3> CA125 predicts and quantifies right heart function and hemodynamic. CA125-BNP congestion phenotypes can be used as a guidance for diagnosis (improved diagnosis of HFpEF and delineation of congestion status) and therapy (LVAD candidate selection and individualized drug therapies and titration).

Characteristics and prognostic value of right ventricular (dys)function in patients with non‐ischaemic dilated cardiomyopathy assessed with cardiac magnetic resonance imaging

AimsIn non‐ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all‐cause mortality and ventricular arrhythmias (VA) was evaluated.Methods and resultsConsecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe‐like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all‐cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all‐cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = −0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = −0.12, P = 0.34). During a median follow‐up of 2.2 years [IQR 1.6–2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49–6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83–22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99–6.57], P = 0.05).ConclusionsRight ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow‐up, RV dysfunction was associated with shorter time to all‐cause mortality and ventricular arrhythmic events.

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 13912: 17-Beta-Estradiol Directly Regulates Microtubule Dynamics: New Insights Into Sex-Differences in Right Ventricular Function in Pulmonary Hypertension

Introduction: Female sex is associated with better right ventricular (RV) function in pulmonary hypertension (PH). The female sex hormone 17-beta-estradiol is postulated to mediate these differences, but the molecular mechanisms underlying these observations are incompletely defined. Interestingly, 17-beta-estradiol induces microtubule depolymerization in cell culture, which may be relevant to RV dysfunction because microtubule remodeling promotes RV dysfunction via dysregulation of junctophilin-2 (MT-JPH2 pathway). We speculate that 17-beta-estradiol modulates the MT-JPH2 pathway and preserves RV function in PH. Methods: Pressure-volume assessments quantified RV function in monocrotaline (MCT) and pulmonary artery-banded (PAB) rats. Immunoblots quantified the tubulin and junctophilin-2 protein content in RV extracts. Echocardiography quantified RV function by RV fractional area change for 379 human PH patients. Sedimentation experiments, fluorescence-based polymerization assessments, and total internal reflection fluorescence (TIRF) microscopy examined the effects of 17-beta-estradiol on microtubules. Results: Female sex results in better RV function and less dysregulation of the MT-JPH2 pathway in both MCT and PAB rats. Moreover, in human PH, female sex was associated with better RV function, which persisted after adjusting for afterload. 17-beta-estradiol inhibited microtubule polymerization in vitro and TIRF microscopy showed 17-beta-estradiol localized to microtubule tips and prevented further microtubule polymerization. Conclusions: Preclinical and human studies show that females are better able to tolerate RV pressure overload. There are blunted microtubule-mediated t-tubule remodeling and preserved RV function in female MCT and PAB rats. In human PH, females have better RV function. These findings may be due to 17-beta-estradiol directly regulating microtubule dynamics as shown by sedimentation and polymerization assays and TIRF microscopy. These results provide additional insights into sex-differences in RV function in PH.

Very low birth weight is associated with reduced right ventricular function detected by strain imaging in early adulthood – findings from a prospective matched cohort study

Abstract Introduction Being born at very low birth weight (VLBW, &amp;lt;1500g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. Strain imaging provides prognostically important information regarding RV dysfunction in diverse cardiopulmonary conditions however, these indices have not previously been described within VLBW cohorts. Purpose To assess differences in right heart function using strain in young adults born at VLBW, compared to normal weight term born controls. Methods The New Zealand Very Low Birth Weight Study has followed all infants born in 1986 with birth weight &amp;lt;1500g. Of 323 survivors to adulthood, 228 (71%) had echocardiograms at 26–30 years which were compared to age and sex-matched term-born, normal-weight controls (n=100). RV global longitudinal strain (GLS) was measured by speckle tracking echocardiography by an investigator blinded to group allocation. Established measures of RV function (fractional area change (FAC), tricuspid annular systolic velocity (RV S') and tricuspid regurgitation velocities) were also obtained. Results VLBW subjects were smaller than their peers as young adults (Table 1). Strain measurement showed reduced myocardial deformation among VLBW subjects (RV myocardial GLS: −22.4% vs −23.5%, p=0.008; RV endocardial GLS: −23.6% vs −24.9%, p=0.005; free wall myocardial GLS −25.2% vs −26.1%, p=0.039; free wall endocardial GLS −26.7% vs −27.9%, p=0.009). TR velocity was higher in VLBW: 224 cm/s v 210 cm/s (p=0.002). RV S', and FAC were not different. Conclusion Young adults born at VLBW have impaired myocardial strain despite preserved RV function as assessed by standard techniques. Echocardiographic strain imaging may be an important tool to detect subclinical RV dysfunction. Graph 1 Funding Acknowledgement Type of funding source: None