Right Ventricular Research Articles

Interventricular abnormal septum displacement as contributory mechanism for impaired peak oxygen consumption and exercise cardiac output response in heart failure

Abstract Background In Heart failure (HF), the role of septum position and abnormal right ventricular (RV) geometry in determining exercise performance is unknown. Especially an abnormal interventricular septal (IVS) position is a well-known sign of RV pressure overload which affects left ventricular filling and output due to interdependence. Aim We postulated that an abnormal septum displacement during exercise and RV geometry alteration would affect peak exercise oxygen consumption (VO2) and cardiac output (CO) increase. Methods 17 HF patients with reduced ejection fraction (HFrEF) (mean age 71±12) underwent a cardiopulmonary exercise testing imaging (iCPET) with RV 3D-imaging analysis and were compared with a control population (mean age 67±14). 3D imaging of the RV chamber was examined off-line using the 4D RV TomTec software and obtained 3D mesh of the RV model using custom software to obtain the mean curvature value of IVS in 4 regions of: inflow tract (RVIT), outflow tract (RVOT), apical and body.We acquired measurements of curvature during end-diastole (ED) and at end systole (ES) phases and obtained a parametric curvature map. Results HF patients typically exhibited an abnormal of septal curve, with a more leftward configuration either at rest and under exercise (rest =−0.01±0.004 at ED, and −0.01±0.006 at ES; peak exercise= −0.01±0.004 at ED, and −0.01±0.004 at ES, Figure) compared to controls (rest=−0.02±0.003 at ED, and −0.02±0.005 at ES; peak exercise −0.02±0.008 at ED, and −0.03±0.006 at ES, Figure). Notably, the degree of the IVS curvature was found to linearly correlate with an impaired gas exchange performance as lower peak VO2 and a limited CO in HF (respectively r=0.62, p<0.001 and r=0.5, p<0.001 at ED during exercise; r=0.34, p<0.001 at ES during exercise, Figure). Conclusions In HF, the RV geometrical alterations reflected by an abnormal IVS displacement appear as novel contributory factors to a reduced exercise performance, impaired oxygen uptake and decreased CO.

Prognostic significance of right ventricular dysfunction in patients with TTR amyloidosis

Abstract Background Transthyretin amyloidosis (ATTR) is increasingly recognized as a cause of heart failure (HF) that now benefits from effective treatment. While the role of right ventricular (RV) systolic dysfunction has been widely accepted as an independent predictor of poor prognosis in HF patients, its implications in ATTR remain poorly understood. Right ventricular free wall strain (FWS) over pulmonary arterial systolic pressure (PAsP) has been recently proposed as an accurate and sensitive tool to evaluate RV function and its coupling to the afterload. Purpose Our study sought to analyze whether indexing FWS to PASP should integrate the set of fundamental data we have to assess the prognosis of ATTR patients. Methods 191 consecutive patients diagnosed with ATTR were enrolled. A comprehensive echocardiographic examination was part of the systematic evaluation. The primary outcome was a composite of cardiovascular mortality and hospitalization caused by heart failure worsening. Results After a median follow-up of 24 months, among patients with ATTR [median age 82 (77, 85), 89.5% male], the primary composite outcome occured in 26%. Cardiovascular mortality rate was 7.3% and the hospital event rate was 18.8%. Tricuspid annular plane systolic excursion (TAPSE), FWS, TAPSE/PAsP and PAsP were univariately significant risk factors for adverse outcome. In multivariate Cox regression analysis, after adjustment of confounding factors, FWS/PASP emerged as an independent predictor of the composite endpoint of cardiac death and rehospitalization (HR 1.61, 95% CI 1.07-2.42, p=0.021). Based on receiver-operating characteristic analysis, the optimal FWS/PASP cut-off value for event prediction was 42.5% (area under the curve = 0.749, p = 0.001). Conclusion Right ventricular function assessed with speckle-tracking echocardiography is an independent prognostic marker for cardiac mortality and heart failure hospitalization in patients with ATTR. FWS/PAsP should be integrated into regular clinical practice for a better evaluation and follow-up of ATTR patients.

Pathobiological characterization of pulmonary hypertension associated with heart failure with preserved ejection fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is an age-related cardiometabolic disease associated with vascular inflammation in cardiac tissue, pulmonary congestion and right ventricular dysfunction. Patients with HFpEF often develop pulmonary hypertension (PH) and right ventricular (RV) hypertrophy. Pulmonary vascular remodeling contributes to combined post- and precapillary PH (CpcPH), which is associated with worse outcome in humans. A recently developed meta-inflammatory murine HFpEF model approximates the characteristics of human HFpEF. Herein, HFpEF is induced by metabolic (high-fat diet (HFD)) and hypertensive stress (inhibition of constitutive NO synthase by Nω-nitro-1-arginomethyl ester (L-NAME)) over a 12-week period of time. With a focus on PH, we have developed a 'three-hit' model based on this model with a supplementary 21- or 42-day hypoxia phase (HFpEF-CpcPH). Methods Adult C57BL/6N mice were fed HFD for 15 or 18 weeks and supplied with L-NAME (0,5g/L or 1g/L) via drinking water, including a final period of 21 or 42 days, respectively, of hypoxia (normobaric, 10 % oxygen) or normoxia. Transthoracic echocardiography was performed using a small animal ultrasound device (Vevo 3100, Visual Sonics) and measurement of right ventricular systolic pressure (RVSP) using a Millar® pressure catheter (Mil-SPR-1000) inserted into the right ventricle. Right ventricular hypertrophy was measured as the ratio of the wet weight of the right ventricle to the left ventricle including the septum (RV/LV+S). Results Administration of HFD and L-NAME had no significant effect on RVSP in either HFpEF-normoxia group (15 weeks (n=8) or 18 weeks (n=5)) compared to the control group (n=8, n=5). 21 days of hypoxia increased RV systolic pressure (RVSP) to 37.05±1.6 (PH, n=8) and 40.33±0.87 mmHg (HFpEF-CpcPH, n=8) respectively, while 42 days of hypoxia caused no further increase (35.1±3.5 mmHg (PH, n=5) and 35.24±3.47 mmgHg (HFpEF-CpcPH, n=4)), respectively. RV hypertrophy (RV/LV+S) was significantly increased after 21 days of hypoxia in HFpEF-CpcPH compared to HFpEF (n=8) (34.42±1.75 vs. 24.93±1.1). Again, 42 days of hypoxia did not lead to a further increase in RV hypertrophy (35.2±3.9 vs. 25.80±4.39) in HFpEF-CpcPH, even though there was a significant difference compared to the HFpEF group. As expected, the heart weight/body weight ratio was significantly increased in HFpEF-CpcPH compared to HFpEF at both time points. However, mice under the prolonged hypoxia phase showed a significantly greater decrease in body weight, which complicates the interpretation of the results. Conclusion In summary, we could show that in the meta-inflammatory HFpEF model no significant PH can be observed within the investigated periods of time. However, a 21 day hypoxia phase was sufficient to induce a HFpEF-CpcPH phenotype. This model provides an important basis to develop new therapeutic approaches.

3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients

Abstract Background RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear. Aim To define new parameters able to detect early RV cardiotoxicity. Methods 51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) >50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline. Results 15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p<0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p<0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%). Conclusion 3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP

Serial changes in left and right ventricular global longitudinal strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, reduces the need for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients and symptoms. As a cardiac myosin inhibitor, mavacamten’s mechanism of action reduces myocardial hypercontractility. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function and can complement left ventricular ejection fraction (LVEF). Objective We sought to assess serial changes in LV and right ventricular (RV)-GLS in patients enrolled in the VALOR-HCM study. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean 60 years, 51% male, LVEF 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). LV and RV-GLS assessment was performed according to the current American and European guideline recommendations using a vendor-neutral post processing software. Non-foreshortened apical (4, 3 and 2-chamber) views were used to obtain peak value of LV-GLS. For RV-GLS, RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. Results Serial changes in LVEF, average LV-GLS, and RV-GLS (4-chamber and free wall) from baseline to week 56 are shown in the Figure. Despite preserved LVEF at baseline, average baseline LV-GLS was abnormal. There were significant and continued improvements in LV-GLS in the total group from baseline to week 56. 12 patients had transient reduction in LVEF (<50%) requiring temporary drug interruption (permanent discontinuation in 3). The LV-GLS in this subgroup was worse at baseline compared to the total study population, with no significant worsening from baseline through week 56. In the overall population, excluding these 12 patients, LV-GLS demonstrated an improvement sustained through week 56. Both free wall and 4-chamber RV-GLS were abnormal at baseline and remained unchanged from baseline to week 56. Conclusions In the VALOR-HCM trial, despite hypercontractile LVEF at baseline, average baseline LV-GLS was worse than normal reference values. Treatment with mavacamten resulted in an improvement in LV-GLS from baseline through Week 56 (with no significant worsening of LV-GLS in the subgroup who experienced any reduction in LVEF <50%), suggesting a favorable long-term impact on regional LV systolic function due to the reduction of cardiac hypercontractility. Additionally, there was no significant detrimental impact on RV systolic function on serial GLS assessment.Serial changes in LV and RV GLS in VALOR

Right ventricular myocardial work in heart failure with preserved ejection fraction: insights from invasive cardiopulmonary exercise testing

Abstract Backgrounds Symptoms of heart failure with preserved ejection fraction (HFpEF) is closely related to elevated pulmonary capillary wedge pressure (PCWP) during exercise. The understanding of right ventricle myocardial work, assessing of right ventricular (RV) function utilizing RV pressure–strain loops, in HFpEF is lacking. Methods The study population underwent invasive cardiopulmonary exercise tests, measuring pressures at rest and during exercise to identify HFpEF. Echocardiography assessed LV and RV parameters. Right ventricular myocardial work was calculated using strain-rate and pressure curves, matching them with ECG data. RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured PCWP at resting and peak exercise. Results Between November 2017 and July 2023, 41 patients with adequate data were enrolled, and 21 were diagnosed with HFpEF. There were no significant differences in various echocardiographic parameters between HFpEF and non-HFpEF groups, except higher post-exercise PCWP and mean pulmonary artery pressure. HFpEF patients had higher RVGWW and lower RVGWE. RVGWW and RVGWE had higher predictive ability for HFpEF diagnosis compared to other echocardiographic parameters. While RVGCW (r = 0.0.504, P = 0.001 and r = 0.430, P = 0.006, respectively) and RVGWW correlated (r = 0.408, P = 0.008 and r = 0.621, P <0.001, respectively) with post-exercise ∆PCWP and exercise PCWP, only RVGWW (β=1.981, P=0.044 and β=4.323, p<0.001) being independently associated with both after adjustment for confounding factors. Conclusions RVGWW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with post-exercise ∆PCWP than other standard echocardiographic parameters in HFpEF.

Prognostic relevance of baseline right ventricular echocardiographic evaluation in patients undergoing valvular surgery with tricuspid intervention

Abstract Background Tricuspid valve (TV) intervention is frequently performed both as part of multivalvular surgery and as an isolated procedure. Tricuspid regurgitation (TR) significantly worsen right ventricular (RV) function, which is a prognostic determinant in many clinical scenarios. Purpose Our aim was to evaluate the relevance of baseline right ventricular (RV) baseline echocardiographic in the prognosis after tricuspid valve surgery (TVS). Methods Retrospective observational study of patients undergoing TVS between 2009 and 2022 in our tertiary centre. Baseline right chambers echocardiographic parameters were evaluated: RV diameters (basal, mid and longitudinal), TAPSE, fractional area change (FAC), Doppler tissue velocity of the tricuspid annulus (RVS´) and free wall- (FW-) and 4 chambers- (4C-) global longitudinal strain (GLS). Likewise, systolic pulmonary artery pressure (sPAP) and left ventricular ejection fraction (LVEF) were collected among other variables. Association of echocardiographic parameters with major clinical events at year was explored. Results Finally 273 consecutive patients (71 ± 10.5 years old, 66.7% female) that underwent valvular surgery with tricuspid intervention were included. Multivalvular procedure was performed in 81.3% (50.6% mitral and tricuspid, 25.6% mitral, aortic and tricuspid and 5.1% aortic and tricuspid) and EuroScore was 5 [3-9]. The most common TV lesion was TR (97.8%), functional in 84.2%. The main surgical technique was tricuspid annuloplasty with prosthetic ring (57.9%). Preoperative echocardiographic parameters are presented in Table. Baseline LVEF was 59 [53-65]%. The most frequent postoperative complication was low output (23.4%) and there was an overall mortality rate of 8.3% during the first year of follow-up. Postsurgical low output state was associated with vena contracta TR (0,78 vs 0,66 cm; p <0.001) and 4C-GLS ((-15.7 vs -17.3%; p= 0.03). None of the baseline echocardiographic variables was associated with early mortality. Conclusions Baseline RV echocardiographic parameters were associated with postoperative low output but not mortality. The relatively preserved RV dimensions and function in our series may explain these findings. Table. Baseline RV echocardiographic variablesTable

Hemodynamic effects of right and biventricular pacing during exercise in hypertrophic obstructive cardiomyopathy

Abstract Background One third of patients with hypertrophic cardiomyopathy present with dynamic left ventricular outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medications, invasive septal reduction, or pacing. The importance of pacing site is unclear, and effects of pacing during physical activity have not been investigated. Purpose To determine the effect of right ventricular (RV) and biventricular (BiV) pacing, respectively, on LVOTO and cardiac output (CO) during exercise in patients with HOCM. Methods Patients with symptomatic HOCM, sinus rhythm, and no bundle branch block, scheduled for alcohol septal ablation (ASA), were eligible for inclusion. The day before ASA, we placed temporary pacing leads in the right atrium, the RV apex, and on the left ventricle’s lateral wall via the coronary sinus. LVOTO was assessed by echocardiography, and CO was measured by thermodilution with a pulmonary artery catheter. Patients performed supine cycling for 2 minutes until heart rate (HR) increased ≥20 bpm. We measured LVOTO and CO in sinus rhythm, and during cycling with atrial sensed RV pacing, and atrial sensed BiV pacing. The order of pacing sites was randomized, and the personnel performing echocardiography and CO measurements were blinded to the order of pacing. Results We included six patients (54±15 years) with a mean maximal left ventricular wall thickness of 16.7±1.8 mm. Resting LVOTO was 55.7±30.9 mmHg. The figures show LVOTO and CO in sinus rhythm (HR 85±10 bpm), RV pacing (HR 90±10 bpm), and BiV pacing (HR 91±9 bpm) during supine cycling. The LVOTO declined from 56±34 mmHg in sinus rhythm to 27±12 mmHg and 25±5 mmHg respectively for atrial sensed RV and BiV pacing. CO remained unchanged during sinus rhythm (9.0±1.2 L/min), atrial sensed RV pacing (9.0±1.7 L/min), and BiV pacing (8.9±1.5 L/min). Conclusion In this ongoing study evaluating cardiac pacing in HOCM, preliminary data indicate that both RV and BiV pacing are effective in reducing LVOTO during exercise, without compromising CO.

Long-acting CRF2 receptor agonist COR-1389 improves cardiopulmonary function parameters in monocrotaline-induced pulmonary hypertension and right heart failure rat model

Abstract Background Pulmonary hypertension (PH) associated with right heart failure (RHF) poses a significant therapeutic challenge. Short term studies have shown that urocortin-2 (UCN-2) administration, either intravenously or subcutaneously, can ameliorate cardiac and/or pulmonary parameters in human heart failure (HF) and in animal models of PH and RHF. Purpose This study aimed to evaluate the potential benefits of COR-1389, a long-acting CRF2 receptor agonist, on cardiopulmonary function and adverse remodeling in a rat model of monocrotaline (MCT)-induced PH and RHF. Method Monocrotaline (40 mg/kg) was administered subcutaneously in rats on Day-0 to induce PH and RHF, while the control group received vehicle. After 14 days, MCT-injected rats were evenly allocated into two groups based on echocardiography parameters of accelerated time/ejection time ratio and tricuspid annular plane systolic excursion (TAPSE), before receiving either COR-1389 (100 ug/kg) or its vehicle subcutaneously every 4 days for 14 days. On Day-28, echocardiography was repeated in all groups, followed by right heart catheterization to directly measure pulmonary hemodynamics. Heart and lung samples were prepared for histological analysis. Results By Day-28, MCT-treated rats exhibited significantly elevated mean pulmonary arterial pressure (mPAP) and right ventricular (RV) mass (Fulton Index/BW), along with decreased RV function (increased TAPSE) and reduced cardiac output (CO) compared to control rats. These changes were accompanied by severe tissue remodeling, including increased vascular muscularization (alpha-smooth muscle actin content) and pulmonary arterial wall thickening, RV fibrosis, and cardiomyocyte hypertrophy. Following 14 days of curative treatment, MCT+COR-1389 compared to MCT, significantly decreased mPAP and RV mass (Fulton Index/BW), while RV function improved (reduced TAPSE) and CO was increased. Moreover, COR-1389 attenuated adverse pulmonary vascular remodeling (reduced muscularization and arterial wall thickening), RV fibrosis, and cardiomyocyte hypertrophy, consistent with its hemodynamic effects. Conclusions Chronic CRF2 agonism with COR-1389 improved dysregulated cardiac and pulmonary function and structure in the MCT rat model, suggesting its potential for the treatment of PH and RHF.

Sex-specific prognosis of right ventricular size measured by 3D echocardiography following isolated tricuspid valve surgery

Abstract Backgrounds Isolated tricuspid valve surgery (ITVS) is considered a high-risk procedure. Right ventricular (RV) size plays a critical role in the prognosis of ITVS patients. The effect of sex differences in the degree of right ventricular（RV）dilatation in ITVS patients has not been established. Purpose The primary objective of this study was to assess in-hospital major adverse events (AEs) following ITVS in women compared with men on the basis of preoperative RV size measured by 3D echocardiography. Methods Consecutive patients undergoing ITVS were identified from a prospectively maintained database.Transthoracic echocardiography was performed the day before ITVS. In-hospital AEs were defined as one of the following occurring before discharge: death, shock, acute renal failure requiring dialysis, or prolonged (>72h) mechanical ventilation. 3D RV parameters including end-diastolic volume (EDV), end-systolic volume (ESV), EDVi (indexed by body surface area), ESVi (indexed by body surface area) and ejection fraction (EF) were calculated using commercially available software. Comparison of the adjusted odds ratios (ORs) generated by multivariate logistic regression of in-hospital AEs between women and men on the basis of baseline RV parameters. Results 59 patients (median age 62 years, 42.37% male, functional tricuspid regurgitation in 62.71%) were finally enrolled. In-hospital AEs were identified in 23 patients (3 death, 5 shock, 5 renal failure, 10 prolonged mechanical ventilation). The risk of AEs was increased from baseline, when the ESV was 69.73 mL for women and 90.66 mL for men. Regarding EDV, the risk for women increased at 130.49 mL compared with 170.36 mL in men. Accordingly, when indexed by body surface area, women had a lower inflection point for both EDVi and ESVi (76.71 mL/m2 vs 91.35 mL/m2, 34.04 mL/m2 vs 52.49 mL/m2). However, there was no inflection point for increased risk with RVEF in either men or women. Conclusion Women undergoing ITVS have a higher risk of in-hospital AEs with smaller RV size. These results support the use of sex-specific thresholds for RV size when making surgical decisions in patients with severe tricuspid regurgitation.Figure 1.Adjusted ORs for RV size.

Prognostic preoperative factors for recurrence of tricuspid regurgitation following annuloplasty: examining the influence of 3d echocardiography

Abstract Introduction The increasing worry revolves around the reappearance of tricuspid regurgitation (TR) following tricuspid annuloplasty (TA) among individuals dealing with functional tricuspid regurgitation (FTR). Despite TA's efficacy as a treatment, a complete understanding of the echocardiographic elements influencing the recurrence of TR is pivotal. This knowledge holds the potential to guide the development of more robust preventive strategies, aiming to ease the incidence of recurrent TR after TA. Aim The aim of this study was to examine the prognostic value of tricuspid valve (TV) and echocardiographic parameters related to both right ventricular (RV) geometry and function. Specifically, our focus is on understanding these relationships in the context of recurrent TR following TA. Methods This prospective observational cohort study aimed to investigate determinants of recurrent TR post-surgical TV repair. The focus was on patients with moderate or severe functional TR related to left heart valvular disease, primarily severe mitral regurgitation, excluding those with ischemic heart disease. The study involved 66 participants, assessed preoperatively with 2D and 3D echocardiography, examining RV and right atrial (RA) geometry, functional, and TV parameters. TR severity followed ESC guidelines. Two groups were formed: effective TA group (50 patients) and recurrent TR group (16 patients), defined by mild to moderate TR and significant moderate-severe TR one year post-surgery, respectively. Statistical analysis employed SPSS software, with adjusted univariate logistic regression considering age and gender. Results Of the patients, 54% were male, with a mean age of 68±9 years. Echocardiography parameters in Table 1 showed no significant differences in gender, left ventricular, atrial geometrical, functional parameters, or preoperative effective regurgitant TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis highlighted RV and RA geometry, along with TV diameter, as predictors for recurrent TR. Notably, 3D TV geometrical parameters had prognostic significance, as confirmed by univariate adjusted logistic regression analysis. Functional RV parameters did not exhibit statistical significance in this analysis. Conclusion In conclusion, the recurrence of moderate-severe functional tricuspid regurgitation following tricuspid annuloplasty is linked to the tricuspid annulus size, as well as the geometry of the right atrium and right ventricle before surgery. Notably, no correlation was identified between the recurrence of TR and alterations in RV function.

Evolution and prognostic relevance of right ventricular morphofunctional parameters in patients undergoing isolated tricuspid valve surgery

Abstract Background Right ventricular (RV) function is key in evolution after isolated tricuspid valve surgery (ITVS). Right ventricular-pulmonary artery coupling (RV-PA coupling), determined with echocardiography as the ratio TAPSE/sPAP, has merged as a relevant functional parameter in many clinical scenarios. Purpose Our aim is to evaluate the prognostic relevance of RV-PA coupling in patients undergoing ITVS. Methods We carried out a retrospective study involving all the patients undergoing ITVS at our tertiary centre. Several RV function measurements were assessed from the baseline echocardiogram (TAPSE, fractional area change (FAC), systolic pulmonary artery pressure (sPAP), tricuspid annulus tissue Doppler velocity (RVS´) and free-wall global longitudinal strain (FW-GLS)) and RV-PA coupling was calculated. Association between RV morphofunctional variables and mortality during one year follow-up was determined. Results 45 patients were included (68 years-old, 51,1% female). The most common TR etiology was functional (51.1%) and 42.2% had previous left-sided valvular surgery. The median Tri-Score was 2 (1-4) points and the most frequent procedure was biological valve replacement (65%). Baseline echocardiographic parameters were as follows: basal 52 (48 – 53.5) mm, mid 40 (36-45.5) mm and longitudinal 73 (68-80) RV diameters, TAPSE 18.1 (15.5-20.7) mm, RVS´ 10.1 (9-12.5) cm/s, FAC 0.5 (0.43-0.57), sPAP 35 (31.5-37.5) mmHg, and FW-GLS - 21.1 (17.2-25) %. During the follow-up 8 (18%) patients died. Solely TAPSE (16 vs 19, p= 0.047) and RV-PA coupling (0.35 vs 0.5; p= 0.035) showed significant differences in mortality among RV echocardiographic parameters. An RV-PA coupling <0.375 mm/mmHg appeared to be the best mortality predictor (RR 1.45; p= 0.04) one year after the intervention (Figure). Conclusions In our series RV-PA coupling has proved to be the best echocardiographic prognostic factor in ITVS, so it could be considered a relevant parameter in risk stratification previous to this surgery. Figure. Kaplan Meier curves of mortality after ITVS by RV-PA coupling.Figure

Reverse RV remodeling after isolated tricuspid valve surgery

Abstract Background Impact of tricuspid regurgitation (TR) on right ventricular (RV) and atrial (RA) size and function is one of the main determinants of prognosis. However, there is scarce data about the recovery of right chambers after isolated tricuspid valve surgery (ITVS). Purpose Our aim is to evaluate postsurgical changes in right chamber morphofunctional parameters by echocardiography after ITVS. Methods We selected all the patients that underwent ITVS in our tertiary centre between 2009 and 2022 excluding those with congenital anomalies. Echocardiographic right ventricular classical parameters (RV diameters, RA area, TAPSE and fractional area change (CAF)) as well as myocardial deformation (free wall (FW)- and 4 chambers (4C)- global longitudinal strain (GLS)) were compared in baseline studies, early and late postsurgical periods. Results Among the 45 patients included (65 ± 2 years-old, 51% female, TRI-SCORE 2 [1-4]) surgical indication was functional TR in 51%, 29% underwent tricuspid valve repair and 71% replacement. The treatment was considered ineffective (postoperative TR ≥ moderate) in 9%. In the early postsurgical phase (1.9 [1.2 – 3] months) a significant reduction in basal (-17%, p<0.01), mid (-15%, p<0.01) and longitudinal (- 7%, p<0,01) RV diameters as well as RA area (-26%, p<0.01) was noted. These changes persist in the late postoperative period for basal (-16%, p<0.01) and mid (-20%, p<0.01) RV diameters and RA area (-19%, p=0.03). RV function parameters suffer significant reduction in the early phases: TAPSE (-39%, p<0.01), FAC (-24%, p<0.01), FW-GLS (-17.1%, p<0.01) and 4C-GLS (-16.3%, p<0.01). In later stages the major worsening in classical parameters persist: TAPSE (-28%, p=0.01) y FAC (-20%. P=0.01). However, strain variables recover to the baseline values. Postoperative RV reverse remodeling is reflected in Table and Figure. Conclusions Postoperative changes in echocardiographic right chambers features after ITVS suggest that myocardial deformation parameters should be the method of choice for follow-up of this surgical procedure. Table. Comparison of baseline and postsurgical echocardiographic parameters. Figure. Echocardiographic parameters evolution.TableFigure

High altitude exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Acute high-altitude exposure increases the risk of acute mountain disease (AMS) and high-altitude pulmonary edema. After the initial exposure to high altitude, mountain climbers are worried about whether they will develop AMS. At high altitudes, there are no accurate indicators to predict the near future occurrence of AMS. Objectives To investigate whether treadmill exercise stress echocardiography at high altitude can predict the occurrence of AMS, and to find out some powerful factors associated with the susceptibility to AMS. Methods 36 healthy lowlanders were taken by bus from sea level to an altitude of 3600 m the next morning, during which they rested overnight at an altitude of 2150 m. Treadmill exercise stress echocardiography was performed immediately upon arrival at 2150 m, and the 2018 Lake Louise Questionnaire Score was performed the next day when arrived at the altitude of 3600 m. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and immediately after exercise. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (SPAP), right ventricular (RV) dimension by 2D, RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI). Pulmonary vascular resistance (PVR) was calculated according to the formula: TRV/RVOT VTI*10+0.16. Mean PAP (mPAP) was calculated as the formula: sPAP*0.61+2. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, SO2 and LV systolic and diastolic function between the two groups (P > 0.05). No significant differences were noted at rest except for TV s' (P < 0.05). Immediately after exercise, TRV, TAPSE, SPAP, mPAP, PVR, and RV area at the end of systole were much higher in AMS (+) group (all P < 0.05). While FAC and TVs’/SPAP were much lower in AMS (+) group (P < 0.05). By multivariable logistic regression model, mPAP immediately after exercise was significantly correlated with AMS occurrence (OR =1.332, 95% CI: 0.669-0.993, P= 003). The cutoff value of mPAP to predict AMS was 32 mmHg (AUC: 0.831, specificity: 86.7%, sensitivity: 76.9%). Conclusions The mPAP immediately after exercise upon arrival at an altitude of 2150 m is a strong predictor of near future AMS, and treadmill exercise stress echocardiography is a simple and non-invasive tool to help mountain climbers avoid more severe mountain sickness.

Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation

Abstract Background The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF. Methods A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure. Results Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1). Conclusions In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.

Echocardiographic predictors of mortality in cardiac intensive care unit patients with pulmonary hypertension

Abstract Background Pulmonary Hypertension (PH) is a diverse condition associated with elevated mortality. We sought to determine the association of Transthoracic Echocardiography (TTE) parameters with in-hospital mortality in patients with PH admitted to Cardiac Intensive Care Unit (CICU). Methods We included 1 Clinic CICU admissions from 2007 to 2018, with available TTE parameters within the first day of CICU admission who had PH defined as an estimated right ventricular systolic pressure (RVSP) ≥36 mmHg. The primary outcome was in-hospital mortality, evaluated using logistic regression. Results We included 3085 unique CICU patients with PH, predominantly WHO group 2 and 3. Median age was 73.7 (63.8, 82.4) years, and 1343 (43.5%) were females. Heart failure (65.6%) and respiratory failure (34.0%) were the most common admission diagnoses. The median RVSP was 47 (41, 56) mmHg, and 1314 (42.6%) had RVSP ≥50 mmHg. A total of 337 (10.9%) patients died during hospitalization. In-hospital deaths had higher RVSP (51 versus 47 mmHg, p <0.001), reflecting higher right atrial (RA) pressure (14 versus 10 mmHg, p <0.001) (Figure). In-hospital mortality increased with worse TTE parameters reflecting Right Ventricle-Pulmonary Artery (RV-PA) coupling, such as Tricuspid Annular Plane Systolic Excursion/ Right Ventricular Systolic Pressure (RVSP), Tricuspid Annular Systolic Velocity (TASV)/RVSP and TASV/ Tricuspid Regurgitation velocity ratios. Conclusion In CICU patients with PH, we have identified the specific Doppler TTE parameters with strong associations with outcomes. Specifically, RA pressure and parameters of RV-PA coupling had the highest discrimination for in-hospital mortality. Comprehensive Doppler TTE is valuable for identification of high-risk PH patients to facilitate further investigation plans, management, and prognostication. Figure: In-hospital mortality in association with right ventricular (RV) function and right atrial pressure (RAP).In-hospital mortality in association wit

Relationship between epicardial adipose tissue and ventricular fibrillation in Brugada syndrome by cardiac computed tomography analysis

Abstract Background Fibrofatty changes in the myocardium of the right ventricular (RV) to right ventricular outflow tract (RVOT) in patients with Brugada syndrome (BrS) may contribute to ventricular conduction delay and ultimately in the development of ventricular fibrillation (VF). In patients with atrial fibrillation (AF), inflammatory infiltration of epicardial adipose tissue (EAT) into the atrial muscle, along with reduced quantity and quality of EAT, has been demonstrated to be associated with the development of AF. We hypothesized that EAT in the RVOT from the RV in patients with BrS may lead to organic abnormalities in the ventricular muscle, resulting in VF. Purpose The purpose of this study was to evaluate the quantity and quality of EAT in patients with BrS using cardiac computed tomography (CT) and to determine the relationship with the occurrence of VF. Methods We retrospectively evaluated 61 of 82 patients with BrS regularly followed in our outpatient clinic from January 2000 to December 2023, who underwent cardiac CT scans. Patients were divided into two groups: those with VF events during follow-up (VF event group) and those without events (VF non-event group). Patient background, various parameters, volume of epicardial adipose tissue (EAT), and CT values from cardiac CT scans were compared between the two groups. EAT volume and CT values were measured for the entire heart and four specific regions: right ventricle (RV-EAT), right ventricular outflow tract (RVOT) to pulmonary artery bifurcation (RVOT-EAT), left ventricle (LV-EAT), and the left coronary artery main trunk circumference (LV summit-EAT) were measured for four specific sites. Results Median age at first diagnosis of BrS was 43 years, 98% were male patients, 41 patients (71%) had symptomatic BrS, and 18 patients (31%) had a family history. During a median follow-up of 72 months (30-136 months), 22 patients (38%) had VF events, including 2 arrhythmic sudden deaths. The median time from diagnosis to the first VF event was 14.3 months (4.3-24.5 months). The VF event group had more overall EAT volume (98.3 cm3 [range: 77.4 to 120.3 cm3] vs. 70.1 cm3 [range: 53.8 to 98.0 cm3], P=0.02) and significantly more RV-EAT volume (18.4 cm3 [range: 11.5 to 28.0 cm3] vs. 11.0 cm3 [range: 7.9 to 18.3 cm3], P=0.008). The CT value of RV-EAT was significantly lower in the VF event group (-83.1±6.1 vs -78.0±6.2, P=0.003), although the RV-EAT/LV-EAT density ratio was not different between the two groups (1.01±0.05 vs 0.99±0.07, P=0.14). On the other hand, the density ratio of RVOT-EAT/LV-EAT was significantly lower in the VF event group (0.95±0.08 vs. 1.00±0.08, P=0.03). Conclusions EAT analysis via CT in patients with BrS revealed that those experiencing VF events during follow-up tended to exhibit greater RV-EAT volume, lower CT values of RV-EAT, and higher CT values of RVOT-EAT density. These findings suggest EAT involvement in VF occurrence in patients with BrS.

Impaired right ventricular strain is associated with worse prognosis in patients with liver cirrhosis

Abstract Introduction Cirrhotic cardiomyopathy is a complication of liver cirrhosis accounting for significant morbidity and associated with reduced patient survival. It is characterized by reduced afterload, increased cardiac output, and diastolic dysfunction. However, there are limited data regarding the prognostic significance of right ventricular (RV) mechanics. Novel echocardiographic techniques such as speckle tracking echocardiography can detect subclinical myocardial dysfunction early in the course of non-ischemic myocardiopathies. Purpose To investigate the prognostic role of RV free wall strain (RVFWS) in patients with liver cirrhosis. Methods We prospectively enrolled 70 patients with liver cirrhosis in stable clinical condition. Patients with coronary artery disease, valvular heart disease, ongoing alcohol consumption or poor acoustic window were excluded from the study. Transthoracic echocardiography was performed and RVFWS was calculated from RV focused 4-chamber views using a dedicated software. Since RVFWS was as expected negative in all patients, absolute values were used for all calculations. Clinical and laboratory examination was also performed in all patients and the Model for End-Stage Liver Disease (MELD) score a widely used tool for assessing liver disease severity was calculated. All-cause mortality at 24 months was the primary endpoint and was available in all patients. Results Mean RVFWS in the cohort was 27.4±6.3% and using a lower normal limit of 20%, reduced RVFWS was detected in six patients. According to the Spearman coefficient analysis, RVFWS was correlated with MELD (rho=0.274, p=0.023) indicating increased values in patients with more advanced liver disease. According to the univariate Cox-regression proportion hazard models RVFWS as a continuous variable was not significantly correlated with worse two year survival (HR: 1.01 (0.95-1.08, p=0.658). Interestingly, among conventional echocardiographic parameters basal RV diameter (p=0.004) and right atrial end-systolic area (p=0.008) were associated with increased risk for the primary endpoint. The association of the primary endpoint with other parameters of RV systolic function was also not statistically significant. The Multivatiate Cox Regression survival analysis, which incorporated age, sex, MELD, hemoglobin, systolic blood pressure and cardiac output, showed that among echocardiographic parameters for the evaluation of the RV, only RVFWS showed a tendency to be associated with worse survival (p=0.062). When patients were stratified into tertiles according to RVFWS values, those in the first tertile (with lower absolute RVFWS values) had significantly increased hazard for the primary endpoint (HR: 5.82, 2.18-15.8, P<0.001) (figure 1). Conclusions RVFWS values are within normal limits in most patients with liver cirrhosis. When adjusted for the severity of the liver disease, reduced RVFWS values are associated with worse prognosis in cirrhotics.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

Prognostic value of combined myocardial performance index in patients with acute ST-elevation myocardial infarction

Abstract Background Myocardial performance index (MPI) also known as Tei index is a unique echocardiographic parameter which can estimate both systolic and diastolic performances of left and right ventricles. We previously suggested the echocardiographic parameter combined MPI (CMPI) as a new predictor of the prognosis of acute ST-elevation myocardial infarction (STEMI). The CMPI is the sum of left ventricular (LV) MPI and right ventricular (RV) MPI (CMPI = LV MPI + RV MPI). We supposed that CMPI might be a better predictor in STEMI, because it reflects both ventricular systolic and diastolic functions. Objectives The purpose of this study is to assess the prognostic value of a new echocardiographic parameter CMPI in STEMI patients calculated in acute phase. Methods 240 STEMI patients who underwent primary PCI have been included in the study. Echocardiography (EchoCG) was performed, and LV MPI and RV MPI were assessed within 24 hours after the symptom onset, prior to primary PCI. The MPI was calculated as the sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT), divided by the ejection time (ET): MPI = (ICT + IRP) / ET. 50 % of the patients had anterior STEMI. 30 patients (12.5%) had concomitant RV myocardial infarction (MI). Patients were divided into two groups: Group 1 – CMPI > 0.9 (110 patients), Group 2 – CMPI ≤ 0.9 (130 patients). Baseline demographic and clinical characteristics were similar in both groups. Also, there were no differences in LV MI localization and concomitant RV MI between the groups. Primary endpoints were in-hospital and the one-year cardiovascular mortality rates. The secondary endpoint was the one-year heart failure hospitalization rate. Results In Group 1 the in-hospital mortality rate was 9.1%, and 3.1% in Group 2 (p = 0.0489). One-year cardiovascular mortality rate was 12.7% in and 5.4%, respectively (p = 0.0465). One-year heart failure hospitalization was also significantly lower in Group 2 (22.7% vs. 12.3%, p = 0.0332). Conclusion CMPI can be offered as a new predictor for the in-hospital and one-year cardiovascular mortality and one-year heart failure hospitalization rate in patients with acute STEMI.