Right Ventricular Dysfunction Research Articles

Abstract 4126672: Clinical Predictors and Outcomes of Catheter-Directed Therapies in Patients with Intermediate-Risk Central Pulmonary Embolism

Background: The management of intermediate-risk pulmonary embolism (PE) is unclear. The use of catheter-directed therapies (CDTs) in these patients has increased. However, their selection is not standardized, and outcomes of CDT compared to anticoagulation alone (ACA) are limited. Research Question: What are the clinical predictors of using CDT and their outcomes compared to ACA? Methods: Single center, 11-year, retrospective study of patients with intermediate-risk central PE. We stratified data by CDT use vs. ACA. We used the simplified pulmonary embolism severity index (sPESI) and right ventricular (RV) dysfunction as surrogates of PE severity and the VTE-BLEED score for baseline bleeding risk. We looked for predictors of CDT use and bleeding complications on multivariate logistic regression analyses. Results: Of 490 patients identified, 110 (22%) underwent CDT (Figure 1, Table 1). Higher BMI (OR 1.04, 95% CI 1.01-1.06; p=0.002), prior venous thromboembolism (VTE) episodes (OR=1.92, 95% CI 1.05-3.50; p=0.032), saddle PE (OR=3.42, 95% CI 2.00-5.85; p<0.0001), RV dysfunction (OR=6.93, 95% CI 3.53-13.57; p<0.0001), and creatinine elevation (OR=1.36, 95% CI 1.13-1.64; p=0.001) were independently associated with CTD use (Table 2). After adjusting for PE severity and bleeding risk, CDT was independently associated with bleeding complications (OR=3.77, 95% CI 1.74-8.15; p=0.001) (Table 3). The overall in-hospital mortality was low (3%, n=13). Conclusions: Higher BMI, prior VTE, saddle PE, RV dysfunction, and creatinine elevation were independently associated with CDT use. The CDT group had more major bleeding without mortality difference compared to ACA. Further studies are needed to standardize the use of CDT in intermediate-risk PE.

Abstract 4136565: Atrial Fibrillation Linked to Right Ventricular Dysfunction in Patients with Acute Pulmonary Embolism

Background: Atrial fibrillation (AF), both new-onset and preexisting, is linked to increased mortality in acute pulmonary embolism (APE). The causal pathway for this association, whether through increased right ventricular dysfunction (RVD) is less well understood. Hypothesis: AF independently predicts RVD in APE patients, affecting mortality and clinical outcomes. Goals: Examine the relationship between AF and RVD to understand its impact on APE survival. Guide further research into optimal APE therapeutic strategies, focusing on early rhythm control. Methods: We conducted a retrospective, multi-center cohort study using data from our Pulmonary Embolism Response Team (PERT) registry. Inclusion criteria included PERT activation and adults over 18. Exclusions were for missing transthoracic echocardiogram (TTE) within 3 days or incomplete TTE data. Patients were categorized by AF status, with RVD assessed by TTE markers. Analysis involved logistic regression and Cox proportional hazards models. Results: Among 535 APE patients, 15% had AF. These patients showed higher unadjusted RVD rates (56% vs. 39%, p=0.006) and significant differences in TTE parameters: TAPSE (1.72 vs. 1.89 cm, p=0.007), S` (11.5 vs. 13.4 cm/s, p=0.0002), and RVOT VTI (13 vs. 14 cm, p=0.019). Adjusted analyses confirmed AF's significant association with RVD (OR 2.32, CI 1.3-4.1), inpatient mortality (OR 4.9, CI 1.5-17, p=0.0106), acute renal failure (OR 2.2, CI 1.2-4.1, p=0.0102), and one-year mortality (HR 1.9, CI 1.06-3.44, p=0.03). Conclusions: AF significantly influences mortality in APE, partly through increased RVD. These findings underline the need for further studies to confirm these relationships and enhance treatment strategies.

Abstract 4136701: A combined approach of cardiac magnetic resonance and CardioMEMS to assess right ventricular dysfunction during exercise in HFpEF-PH

Background: Right ventricular dysfunction (RVD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with shortened life expectancy. Early identification of these at-risk patients could facilitate the initiation of future treatments. Evaluating the RV during exercise has proven to enhance the diagnostic accuracy in revealing RVD that is not detectable at rest. The CardioMEMS device has emerged as a non-invasive tool to remotely monitor pulmonary artery pressures (PAP) and enable early identification of clinical worsening. Research Questions: Using a hybrid approach of combined real-time CMR-derived volume measurements with CardioMEMS-derived PAP measurements, we aimed to identify RVD during exercise which is not detectible at rest in a population of patients with HFpEF and pulmonary hypertension (PH). Methods: In this prospective cohort study, we used a hybrid approach of two consecutive exercise tests in HFpEF patients ( Figure 1 ). First, PAP were measured using the CardioMEMS signal on a supine bike at rest, and 25%, 50%, and 75% of peak power output determined previously on an upright cycle ergometer. Subsequently, volumes were derived by CMR at rest and during exercise at 25% and 50% of peak power output. The RV end-systolic pressure-volume relationship (RVESPVR), a surrogate of RV contractility, was calculated as mean PAP divided by RV end-systolic volume. RV contractile reserve, as a marker of RVD during exercise, was calculated as the ratio of peak exercise to resting RVESPVR, with values < 2.0 indicating impairment. Results: Fourteen patients with HFpEF-PH were included (age 76.6±6.9 years, 57% women). Eleven (79%) had impaired RV contractile reserve during exercise ( Table 1 ). Although not significant, RVESPVR at rest tended to be better in the group with RVD during exercise (0.47±0.17 vs 0.27±0.03; P=0.070). Peak VO 2 was significantly reduced in patients with RVD during exercise (13.1±2.0 vs. 18.6±6.4%; P<0.021). Conclusion: A new hybrid approach combining cardiac MRI and CardioMEMS is feasible during exercise in HFpEF patients and identifies RVD in approximately eighty percent of patients with HFpEF and elevated mPAP at inclusion. Evaluation of RV contractility at rest showed a discordant trend, pointing out the need to test the RV during exercise. Further research is needed to determine if this approach can predict progression of RVD over time and serve as a risk stratification tool for these patients.

Abstract 4132909: Hemodynamic Indices of Right Ventricular Function Differentially Predict Adverse Clinical Outcomes in Heart Failure with Preserved vs Reduced Ejection Fraction

Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF<50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI <450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p<0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p<0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p<0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.

Abstract 4114220: Majority of Patients with New Ventricular Dysfunction After Acute COVID-19 Infection Did Not Have Cardiac Recovery

Background: It is still not well understood whether cardiac injury observed during acute COVID-19 infection extends after recovery from the initial viral infection. The purpose of this study was to determine the incidence of left and right ventricular dysfunction in patients hospitalized with acute COVID-19 and evaluate for cardiac recovery. Methods: A multicenter, retrospective cohort study was conducted. Adult patients were identified by hospitalizations using ICD-10 code U07.1 from March 2020 to October 2021. Patients were included if they had: 1) acute COVID-19 infection confirmed by RT-PCR and 2) a transthoracic echocardiogram (TTE) performed during their hospitalization. Clinical and echocardiographic data were collected and analyzed. Longitudinal TTE parameters were obtained from follow-up studies performed after discharge. Results: A total of 750 patients (mean age 64.3 ± 15.3 years, 60.0% male) were included. The average time to follow-up TTE was 8.7± 7.4 months. 133 patients (17.7%) had new LV dysfunction seen on TTE ( Figure 1 ). LV recovery (defined as normalization of LVEF or improvement of LVEF by > 10% from baseline) was observed in 28 of 74 (37.8%) survivors. 9 of 26 patients (34.6%) who had a follow-up TTE <6 months post-discharge recovered their LV function, while 19 of 48 patients (39.6%) who had a follow-up TTE ≥6 months had LV recovery. 94 of 725 patients (13.0%) with reported RV parameters had new RV dysfunction seen on TTE. RV recovery (defined as normalization of RV function) was observed in 11 of 38 (28.9%) survivors. 6 of 18 patients (33.3%) who had a follow-up TTE <6 months post-discharge recovered their RV function, while 5 of 20 patients (25%) who had a follow-up TTE ≥6 months had RV recovery. Conclusions: Most surviving patients who developed new LV or RV dysfunction did not recover their ventricular function at follow-up, but recovery extended beyond 6 months follow-up.

Abstract 4138386: Deep Learning-Enabled Assessment of Right Ventricular Function Using 2D Echocardiograms Improves 1-Year Mortality Prediction in Patients with Severe Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion (TAPSE). Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2D echocardiographic videos, with similar diagnostic accuracy as 3D imaging. Aims: This study aimed to evaluate the prognostic utility of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER. Methods: This multicenter registry study analyzed the associations between the predicted RVEF values and 1-year mortality in patients with severe MR undergoing TEER. To predict RVEF, 2D apical four-chamber view videos from preprocedural transthoracic echocardiographic studies were exported and processed by a rigorously validated deep learning model. Results: From 1,366 patients undergoing TEER between 2017 and 2023, good-quality 2D apical four-chamber view videos could be retrieved for 1,154 patients (84.5%). Survival at one year after TEER was 84.7%. The predicted RVEF values ranged from 26.6% to 64.0% and correlated only modestly with TAPSE (Pearson correlation coefficient R: 0.33; p -value: <0.001). Importantly, predicted RVEF levels were superior to TAPSE levels in predicting 1-year mortality after TEER (area under the curve: 0.687 vs. 0.625; p -value: 0.029). Furthermore, Kaplan-Meier survival analysis revealed that patients with preserved RV function (defined as a predicted RVEF of ≥45%) had significantly better 1-year survival rates than patients with reduced RV function (92.1% [95% CI: 89.5-94.7%] vs. 80.3% [95% CI: 77.4-83.3%], respectively, hazard ratio for 1-year mortality: 2.67, p -value: <0.001). Conclusion: Deep learning-enabled assessment of RV function using standard 2D echocardiographic videos can refine the prognostication of patients with severe MR undergoing TEER. Thus, it can be used to screen for patients with RV dysfunction who might benefit from intensified follow-up care.

Abstract 4117657: Targeting GPR39 for Hypoxia-induced Pulmonary Hypertension in Mice

Background: Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells. Hypothesis: We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction. Methods: Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O 2 ). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O 2 ). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated. Results: Heart rate and systolic blood pressure were not different between the 4 groups . WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3). Conclusions: By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.

Abstract 4136452: Acute Cardiac Function Change After Catheter Ablation of Ventricular Arrhythmias in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by fibrofatty replacement of myocardial tissue, creating areas of electrical heterogeneity and increasing the risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Catheter ablation is commonly performed in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) for management of ventricular arrhythmias (VAs). Whether catheter ablation affects cardiac function post-procedurally is uncertain. Research Question: Does catheter ablation for ARVC result in acute change in cardiac function? Goals/Aims: To assess the impact of catheter ablation for VAs on cardiac function in the acute post-procedure setting. Methods: This retrospective study included patients with ARVC who underwent catheter ablation for VAs at Mayo Clinic. Cardiac function was assessed on pre- and post-procedure transthoracic echocardiograms (TTEs). Post-procedure TTEs were obtained within 4 weeks after the ablation procedure. Right ventricular (RV) enlargement and systolic dysfunction were evaluated as continuous variables (0=none, 1=mild, 2=mild-moderate, 3=moderate, 4=moderate-severe, 5=severe). Results: The study included 32 patients who underwent a total of 44 ablations. Mean age at the time of ablation was 49±16 years, and 24 (75%) were male. After a mean follow-up duration of 2.6±5.5 days, there was a significant worsening in mean RV dysfunction (1.6±1.5 to 2.0±1.4, P = 0.001). There were no significant changes in mean left ventricular ejection fraction (LVEF), left ventricular (LV) dimensions, and RV size. 6 (14%) patients had a >5% decline in LVEF, and 14 (32%) patients had worsening RV function. Transient inotropic support was required in 4 (9%) patients. Conclusion(s): This study is the first to assess the acute impact of catheter ablation for VAs on cardiac function in ARVC patients. These results underscore the importance of careful post-procedure monitoring and planning of the ablation target in these patients to avoid excessive ablation and therefore impairment in cardiac function.

Abstract 4114497: Shape Variations in Right Ventricular 3D Geometry are associated with adverse outcomes in Hypoplastic Left Heart Syndrome Patients: A Fontan Outcomes Registry using CMR Examination (FORCE) Study

Introduction: Right ventricular (RV) function is critical to the long-term health of patients with hypoplastic left heart syndrome (HLHS). However, conventional measurements do not consider the range of RV morphology that may impact RV function and lead to adverse outcomes. In this study, we determined associations between RV shape and clinical outcomes of HLHS using statistical shape modeling (SSM) and a large cardiac magnetic resonance (CMR) multicenter registry. Methods: Three hundred and twenty-eight studies from unique HLHS patients in the F ontan O utcomes R egistry using C MR E xaminations (FORCE) were post-processed by a core lab at one institution, including volumetry and strain analysis. 3D end-diastolic models of RV were reconstructed using Mimics (Materialise). SSM was performed via Shapeworks Studio (NIH/NIGMS CIBC) to derive mean template and quantified shape variations (shape mode) representing deviation from the mean. RV shape relationship with mortality/heart transplant was assessed using bivariable/multivariable analyses with stepwise model selection. Results: The mean template from all 328 patients resembled a circumferentially dilated RV with loss of concavity in septal wall (Fig A). Several generalized variants were identified (Fig B), particularly p1 – a sigmoidal / “apical bulge” variant where the RV apex dilates and "wraps” around the hypoplastic left ventricle (Fig C). Twenty-eight patients (8.5%) experienced mortality/heart transplant at 2.5±2.4 years after CMR. On bivariable analysis, p1 was associated with mortality/heart transplant, along with larger indexed RV end-diastolic volume/mass and reduced global circumferential strain. On multivariable analysis, p1 and indexed RV mass were associated with mortality/heart transplant (Table). Conclusions: Statistical Shape Modeling can define the “usual” RV shape of HLHS. A sigmoidal shape variant is associated with adverse outcomes. SSM may provide patient-specific metrics to define RV dysfunction in HLHS.

Tricuspid Valve Reconstruction in Patients with Right Heart Decompensation Due to Severe Tricuspid Regurgitation on LVAD Support

Background/Objectives: Right ventricular (RV) dysfunction after left ventricular assist device (LVAD) implantation is associated with reduced survival and affects duration of hospitalization. Some patients with RV dysfunction on LVAD have significant tricuspid valve regurgitation (TR) with concomitant signs of RV failure. In these cases, tricuspid valve repair (TVR) may minimize clinical signs of RV failure. Methods: We report on two patients (one female, one male) developing significant TR receiving TVR through a right thoracotomy on LVAD support. Results: The time between LVAD implantation and TVR was 4 months and 50 months, respectively. The female patient could be discharged from hospital without TR and any signs of RV dysfunction. The male patient died 13 days later due to septic shock following mesenteric ischemia. At this time, echocardiography showed a competent tricuspid valve. Conclusions: In conclusion, these results provide insight into the clinical judgment of when TVR should be attempted. They suggest whether TVR may be a strategy to avoid hospitalization, minimize the clinical signs of RV insufficiency and improve quality of life in patients on LVAD support with severe TR and clinical signs of right heart dysfunction.

Prevalence and Prognostic Significance of Right Ventricular Dysfunction in Patients With Severe Low-Flow, Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Whether the presence of right ventricular (RV) dysfunction may influence the clinical outcome of patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR) has not yet been established. This study included consecutive patients with LFLG-AS undergoing TAVR at 2 high-volume Italian centers. RV dysfunction before TAVR procedure was defined as tricuspid annular plane systolic excursion assessed by transthoracic echocardiography lower than <17 mm. The primary outcome was all-cause death at 1 year. The propensity score weighting technique was implemented to account for potential selection bias between patients with and without RV dysfunction. A prespecified subgroup analysis was conducted to evaluate the consistency of the results in patients with classical and paradoxical LFLG-AS forms. This study included 392 patients; of them, 97 (24.7%) patients showed RV dysfunction before TAVR. At propensity score-weighted adjusted Cox regression analysis, RV dysfunction, according to dichotomous definition, was associated with an increased risk for the primary outcome (adjusted hazard ratio [HR], 3.11 [95% CI, 1.58-6.13]), cardiovascular death (adjusted HR, 3.26 [95% CI, 1.58-6.72]), and major adverse cardiovascular and cerebrovascular events (adjusted HR, 3.39 [95% CI, 1.76-6.53]). Conversely, no difference was detected for the risk of stroke and of permanent pacemaker implantation. No significant interaction of the classical and paradoxical LFLG-AS subgroups was detected for all the outcomes of interest. This study suggests that RV dysfunction echocardiographically assessed by tricuspid annular plane systolic excursion may improve the prognostic stratification of patients with LFLG-AS undergoing TAVR.

Systolic and global right ventricular functions of children with bronchial asthma as compared with those of healthy controls using echocardiography: a single-centre cross-sectional observational study from Nigeria

BackgroundAsthma is the most prevalent chronic airway condition in children. It is characterised by hyperresponsiveness of the small airways leading to airway narrowing, which is usually reversible, with or without treatment. Asthma is known to cause right ventricular dysfunction, but not much is known of this effect among children with highest burden of asthma. The aim of this study is to compare the right ventricular functions of children with asthma, aged 6– ≤ 13 years, with those of their age and sex-matched apparently healthy control using transthoracic echocardiography. The systolic and global right ventricular functions were assessed using Tricuspid Annular Plane Systolic Function (TAPSE) and Tei index, respectively.ResultsSeventy cases and 68 controls were included in the final analysis of the results. The male-to-female ratios are 1.9:1 and 2:1 for the cases and controls, respectively, and their mean age were 8.82 (± 2.28) and 9.05 (2.50) years. There was no statistically significant difference between their sex (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document}/P = 0.810/0.85) and their mean age (P = 0.554). The mean TAPSE of the cases (20.16 ± 2.15 mm) and the controls (20.28 ± 2.71 mm) did not differ significantly (P = 0.74), but the mean Tei index of the cases (0.56 ± 0.16) was significantly higher than that of the control (0.50 ± 0.10) (P = 0.007). Among the asthmatics, 17.1% (12/70) and 2.9% (2/70) had global and systolic RV dysfunctions, respectively; 2.9% (2/70) of the controls had RV global dysfunctions, but none had RV systolic dysfunction. The global dysfunction among the asthmatics was significantly associated with their age range and frequency of hospitalisation (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document} /p of 6.051/0.014 and 7.209/0.021, respectively), and significantly correlates with their Body Mass Index, and peripheral oxygen saturation (r/P of −0.236/0.049 and − 2.490/0.038, respectively). None of the participants had right ventricular systolic dysfunction.ConclusionThis study shows that asthmatic patients have global RV dysfunction, and it is suggested that better control of asthma would preserve cardiac function.

Supplemental oxygen for pulmonary embolism (SO-PE): study protocol for a mechanistic, randomised, blinded, cross-over study

BackgroundAcute pulmonary embolism (PE) mortality is linked to abrupt rises in pulmonary artery (PA) pressure due to mechanical obstruction and pulmonary vasoconstriction, leading to right ventricular (RV) dilation, increased RV...

Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial.

There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; P=0.04) with LBMT vs CDT and less postprocedural ICU utilization (P<0.001), including admissions (41.6% vs 98.6%) and stays >24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies, nor in a secondary WR endpoint including the first 4 components (WR 1.34 [95% CI: 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs 20.1±5.1; P<0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs 26.4%; P<0.001), NYHA classifications (16.3% vs 27.4%; P=0.002), and RV dysfunction (42.1% vs 57.9%; P=0.004). RV/LV ratio reduction was similar (0.32±0.24 vs 0.30±0.26; P=0.55). LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% vs 7.9%; P=0.03), while 30-day mortality was similar (0.4% vs 0.8%; P=0.62). PEERLESS met its primary endpoint in favor of LBMT vs CDT in treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding.

Impact of late reperfusion therapy in patients with inferior ST-segment elevation myocardial infarction and right ventricular dysfunction: one size never fits all

Abstract Background A significant proportion of ST-segment elevation myocardial infarction (STEMI) patients present late to the emergency room with limited evidence of benefit of reperfusion after 12 hours of symptom onset. Inferior myocardial infarction (MI) with right ventricle (RV) dysfunction is associated with high morbidity and mortality, however, the RV has a unique physiology that allows it to withstand ischemia better and recover faster. Purpose To compare adverse in-hospital cardiovascular events in latecomers with inferior STEMI and RV dysfunction admitted to a cardiovascular intensive care unit (CICU) from a low-to-middle-income country, who underwent late reperfusion treatment versus conservative treatment. Methods A retrospective cohort study was conducted from March 2022 to April 2023. Patients with inferior STEMI and RV dysfunction who received late reperfusion treatment were included. RV dysfunction was defined as a TAPSE &amp;lt;17 mm, tricuspid annular systolic velocity on TDI &amp;lt;9.5 cm/s, or a fractional area change &amp;lt;35%. Late reperfusion was defined as primary percutaneous coronary intervention (PCI) performed after 12 hours of symptom onset or rescue PCI after 12 hours of failed fibrinolysis. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were cardiovascular death, reinfarction, stroke, cardiogenic shock, and mechanical complications. Results During the specified period, a total of 106 patients met the inclusion criteria from a total of 1,786 patients admitted to the CICU in our center. Only 60 patients underwent late PCI, accounting for 56% of the cases, with a median time of onset of symptoms to reperfusion of 19.4 hours (IQR: 15.7, 30.2). The average age was 66.5 ± 10.4 years, and 28% were women. Although the all-cause death rate was lower among late PCI group (13.3% vs 26.1%; p=0.096), this difference did not reach statistical significance in the bivariate analysis. Stratified by cardiogenic shock, a lower rate of all-cause mortality was also observed (33% vs 55%, p=0.15). The incidence of reinfarction was significantly lower in the late PCI group (0% vs 13%, p=0.004). In the multivariate analysis, adjusting for those who underwent PCI between 12-48 hours, revascularization of latecomers was independently associated with a significant reduction of mortality (adjusted OR 0.22; 95% CI 0.05-0.92; p=0.038). In a post-hoc analysis, late PCI showed a lower association with the composite outcome of all-cause mortality and reinfarction (adjusted OR 0.16, 95% CI 0.04-0.56; P=0.004). Conclusion(s) Our study demonstrates that implementing a reperfusion strategy in latecomers with inferior STEMI and RV dysfunction significantly reduces the risk of in-hospital mortality and reinfarction. This suggests a potential benefit of expanding the therapeutic window for PCI in this high-risk population. However, prospective studies are needed to conclude these preliminary findings.

CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study

Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP &amp; RV remodeling

Prognostic implications of right ventricular dysfunction in degenerative mitral regurgitation

Abstract Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with survival in patients with DMR. Methods We used data from the Mitral Regurgitation International DAtabase-Quantitative (MIDA-Q) which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 4,379 (mean age: 67 years, 64.6% males, follow-up:5.3[3.3-8.2]years) consecutive patients with significant (≥moderate) DMR was included and long-term survival was analyzed. Results RVD, identified in 584(13.3%) patients, was associated with reduced 10-year survival (49±3% vs. 67±1%; p&amp;lt;0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures and surgery (adjusted HR[95%CI]=1.55[1.31-1.84]; p&amp;lt;0.001). This excess mortality was observed under medical management (adjusted HR[95%CI]=1.39[1.12-1.72]; p=0.003) and after surgical correction of mitral regurgitation (adjusted HR[95%CI]=1.56[1.08-2.27]; p=0.019). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 10-year survival (73±4% vs. 38±4%; p&amp;lt;0.001), even after adjustment (adjusted HR[95%CI]=0.53[0.35-0.81]; p=0.003) despite an increase of 1-month post-operative mortality (5% vs 2.2% for patients without RVD; p&amp;lt;0.001). Conclusions RVD is observed in 13.3% of significant DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision-making process.determinant ans prognosis of RVD in MR

Electrocardiographic markers of depolarization and repolarization in lead V1 predict right ventricular dysfunction in patients with heart failure

Abstract Background Right ventricular (RV) dysfunction is an important predictor of survival in patients with heart failure (HF) with both preserved (HFpEF) and reduced ejection fraction (HFrEF). To date there is limited data on the value of the electrocardiogram in predicting RV function. Purpose Given these considerations the aim of our study was to assess the possible relationship between several electrocardiographic (ECG) parameters and right ventricular function evaluated by echocardiography. Methods We included 109 patients (age 61±14 years, 68men) of whom 89 had HF (HFpEF N=62 and HFrEF N=27) and 20 patients without HF. Twelve-lead ECG and echocardiograms were performed in all patients. We assessed echocardiographic parameters of global and regional RV function. Results Time to Intrinsicoid deflection in lead V1 (TID-V1) and the QTc interval measured in lead V1 (QTc-V1) were significantly more prolonged in patients with HF vs. patients with no HF (36±24ms vs. 23±15ms; p=0.03, and 450±40ms vs. 427±20ms; p=0.047 respectively). TID-V1 correlated significantly with the tricuspid annulus systolic excursion (TAPSE) and RV fractional area change (FAC; r=-0.31; p=0.02, and r=-0.35; p=0.029 respectively). QTc-V1 correlated with parameters of global and regional RV function including FAC, RV apex longitudinal strain, RV free wall strain, and global RV strain (r=-0.42; p=0.0004, r=0.35; p=0.0032, r=0.21; p=0.045, and r=0.41; p=0.0005). RV dysfunction as defined by RV-FAC&amp;lt;35% was predicted by TID-V1 &amp;gt; 30ms with a sensitivity of 61% and specificity of 75%; AUC=0.752 and by QTc-V1&amp;gt;440ms with a sensitivity of 80% and specificity of 57%; AUC=0.888, and by a multivariate logistic regression model that also included TID-V1 and QTcV1, age, TAPSE, and LV ejection fraction with an AUC=0.967 (Figure). Conclusions Lead V1 time to intrinsic deflection and QTc-V1 predict RV dysfunction independent of echocardiographic parameters of ventricular function in patients with HF.

Prognostic impact of the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in acute pulmonary embolism

Abstract Background Currently available risk stratification models for acute pulmonary embolism (PE) include hemodynamic status, cardiac biomarkers, right ventricle (RV) dysfunction on imaging, and clinical scores. Focusing on length-tension relationship of the ventricle might have a superior predictive capability over RV dysfunction in terms of mortality and classification of patients with acute PE. In this study, our hypothesis suggests that tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio has superior predictive capability for in-hospital mortality in patients with acute PE compared to TAPSE or sPAP as distinct measures. Methods This single-center study comprised retrospectively evaluated 703 patients referred to our tertiary cardiovascular center with acute PE. We divided patients into quartiles by TAPSE/sPAP ratio. Different models were developed to quantify the predictive relationship between in-hospital death and echocardiographic measurements. A base model was created with variables including risk status and RV/LV ratio &amp;gt;1. Then, to evaluate the predictive contribution of each measurement; TAPSE/sPAP, TAPSE, and sPAP were sequentially added to the base model. After that, the performance of each model was evaluated. Results Predictive and discriminative power was the highest in model containing TAPSE/sPAP. There was still a significant inverse association between TAPSE/sPAP and risk of in-hospital death even after adjusting by risk status and RV/LV ratio &amp;gt;1. ROC curve analysis for TAPSE/sPAP revealed the best cut-off value as 0.34. Conclusion The outcomes of our study reveals that the ratio of TAPSE/sPAP serves as a more potent predictor of mortality than either of the two measurements taken separately. The interpretation and utilization of the TAPSE/sPAP cut-off value in acute PE can assist in identifying patients at risk of deterioration and guide the consideration of more intensive treatment options across all risk groups.

Cardiovascular comorbidities and risk stratification in normotensive acute pulmonary embolism patients with right ventricular dysfunction and normal cardiac troponin: insights from a regional registry

Abstract Background Acute pulmonary embolism (PE) management guidelines categorize normotensive patients with right ventricle dysfunction (RVD) and normal cardiac troponin (cTn) as intermediate low risk. This study explores the prevalence of cardiovascular comorbidities and their impact on risk stratification in this specific cohort. Purpose To investigate the characteristics of normotensive acute PE patients with RVD and normal cTn, emphasizing the role of pre-existing cardiovascular diseases in determining the intermediate-low risk status. Methods A total of 1675 PE patients from a regional registry were screened, excluding high-risk and intermediate-high-risk cases. Among the remaining 400 normotensive patients with RVD, 353 with echocardiography and normal cTn were included. Patients were categorized into low or intermediate-low risk based on RVD presence. Cardiovascular comorbidities were assessed, and logistic regression analyzed their association with intermediate-low risk. Results Intermediate-low-risk patients (n=137) exhibited significantly higher rates of chronic heart failure, arterial hypertension, coronary artery disease, diabetes, and atrial fibrillation compared to low-risk patients (n=216). A substantial 77.4% of intermediate-low-risk patients had at least one cardiovascular comorbidity, significantly elevating the risk of RV dysfunction (adjusted OR 2.954, p&amp;lt;0.001). The all-cause hospital mortality was 5.1% in intermediate-low-risk and 1.4% in low-risk PE. Conclusions Normotensive acute PE patients with RVD and normal cTn are predominantly burdened with chronic cardiovascular conditions. The majority of intermediate-low-risk patients have at least one cardiovascular comorbidity, indicating an increased risk of death during hospitalization compared to low-risk patients. This study underscores the necessity for nuanced risk stratification considering pre-existing cardiovascular diseases for tailored and effective management. These findings have important implications for optimizing treatment strategies and improving outcomes in this high-risk population.