Worse Right Ventricular Function Research Articles

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.

Increased bone morphogenetic protein 10 in precapillary pulmonary hypertension patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Scientific Research: NWO-VICI num. 918.16.610 and NWO-VIDI num. 917.18.338. Dutch Heart Foundation Dekker senior post-doc grant num. 2018T059 and the Netherlands CardioVascular Research Initiative: CVON-2017-10 DOLPHIN-GENESIS and CVON-2018-29 PHAEDRA-IMPACT. Fundació La Marató de TV3 num.202038. The Spanish Ministry of Science through the Ramón y Cajal grant num.RYC2021-030866-I. Introduction Precapillary pulmonary hypertension (PH) results in increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein (BMP) 10 (BMP10) in adults, mostly produced by RA cardiomyocytes. The major predisposing risk factor for PH involves loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, through which BMP10 and BMP9 transduce signals. Purpose The aim of this study was to investigate if BMP10 expression is altered in PH, and whether BMP10 signaling activity associates with right ventricular (RV) adaptation, RA function and disease progression. Methods We investigated BMP10 gene and protein expressions in RA tissue. We determined BMP10 and BMP9 plasma levels by ELISA. We studied BMP10 signaling activity in PH and CTEPH patients before and after pulmonary endarterectomy (PEA). Results BMP10 mRNA, protein and activity were significantly increased in the PH right atrium. While circulating levels of BMP10 and BMP9 proteins were increased, no significant changes were observed in BMP10 signaling activity between PH and controls. In a cohort of CTEPH patients, BMP10 signaling activity was reduced after PEA which coincided with improved hemodynamics and RV function. Interestingly, high BMP10 activity was associated with reduced RV function and adaptation, increased RA dilation and decreased RA function. No associations were observed with hemodynamics or general disease markers. Conclusions RA BMP10 expression and plasma levels are increased in precapillary PH. High BMP10 transcriptional activity was associated with worse RV function, RV adaptation, RA dilation and RA function. Future studies are needed to further understand the mechanism underlying BMP10 secretion and function in PH.

Prognostic value of right atrial strain in patients with isolated severe tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Moderate or severe isolated Tricuspid regurgitation (TR) can lead to right ventricular (RV) dysfunction and adverse outcome. Only few patients with significant TR undergo intervention, and the optimal timing for intervention remains elusive. The right atrium (RA) is the receiving chamber of the tricuspid regurgitant volume. Changes in RA function has been described in chronic severe TR, specifically reduction in right atrial reservoir strain (RARS). The aim of this study was to evaluate the prognostic value of RA function in a cohort of patients with isolated severe TR. Materials and Methods Clinical, laboratory and echocardiographic data from 105 consecutive patients with isolated moderate-severe TR (grade≥+3) were analyzed. RARS was evaluated by two-dimensional speckle-tracking echocardiography using a semi-automated software (TOMTEC, Philips). The cohort was divided into two groups: RARS value above or below 10.9%, according to an optimal threshold obtained by a receiver operating characteristic (ROC) curve. Results and discussion A total of 105 patients (mean age 79Y, 59% female) were included. Compared with patients with higher RARS, patients with RARS≤10.9% had higher rate of atrial fibrillation and worse RV function. Lower RARS was also associated with larger inferior vena cava diameter, abnormal cholestatic liver enzymes and higher rate of diuretic use. During a median follow-up period of 19 months (IQR:8–25), 39 (37%) patients died. Patients with RARS ≤10.9% had significantly lower survival rates compared with patients with RARS>10.9 (60% vs. 20%; P<.001). A multivariable analysis (including age, RV longitudinal strain, systolic pulmonary artery pressure and atrial fibrillation) showed that lower RARS was independently associated with higher all-cause mortality (OR 2.47, 95%CI [1.07–6.06]; P=0.03). Conclusions Impaired RA function assessed by echocardiographic RA reservoir strain is independently associated with all-cause mortality in patients with isolated severe TR. Serial measurement of RARS can potentially aid in optimizing timing for intervention in patients with TR.

PO-01-024 FEASIBILITY, SAFETY AND LONG-TERM OUTCOMES OF LEFT BUNDLE BRANCH PACING – THE AUSTRALIAN EXPERIENCE

Left bundle branch pacing (LBBP) has shown to be safe and effective, observing low and stable pacing thresholds. Considering it being a relatively new technology, long-term outcomes of this pacing modality is still unclear. We aimed to prospectively assess the efficacy, long-term effects, and safety of LBBP in consecutive patients requiring right ventricular pacing. Heart failure patients and patients requiring cardiac resynchronisation therapy were excluded from this study. In this cohort study, consecutive patients requiring pacing therapy were enrolled. Permanent LBBP leads were implanted if the left bundle branch (LBB) capture threshold was <2.5V/0.5 ms. Pacing parameters, ECG parameters, complications and echocardiographic measurements were assessed during follow-up. In 156 enrolled patients (67±7 years of age), LBB capture was acutely achieved in 147 (94%) patients, and 134 (91%) patients received permanent LBBP. 13 (9%) patients did not receive permanent LBBP, due to no LBB capture (n=6), high LBB capture thresholds (n=5) and fixation failure (n=2). The median follow-up period of permanent LBBP was 55±6 months. LBB capture threshold remained stable with acute threshold of 1.82±0.91 V/0.5 ms to 2.09±0.12 V/0.5 ms at 5-year follow-up (p>0.05). Mean percentage right ventricular pacing was 33±9%. Mean paced QRS duration at implant was 93±6 ms and at final follow-up was 101±3 ms (p>0.05). Mean left ventricular ejection fraction at baseline was 51.4±2.1%, which remained stable at 54.7±1.8% at final follow-up (p>0.05). At baseline, left atrial indexed volume was 31±2mL/m2 and at final follow-up remained stable at 33±1.5mL/m2 (p>0.05). No patient had worsening of right ventricular function, mitral or tricuspid regurgitation. This large observational study suggests that left bundle branch pacing is feasible, safe and effective with high success rates and low complication rates during long-term follow-up. Therefore, left bundle branch pacing appears to be a reliable method for physiological pacing in patients with bradycardia indication.

Long term recovery of right ventricular function after treatment of intermediate and high risk pulmonary emboli

IntroductionPulmonary embolism (PE) is a common and significant source of mortality and morbidity worldwide. A subset of patients with PE, particularly those who have intermediate and high risk events, are at increased risk for long-term right ventricular (RV) dysfunction; however, the impact of novel advanced therapies used for acute PE, including catheter-directed intervention, on long-term RV function remains uncertain. We sought to determine whether use of advanced therapies (catheter-directed intervention or systemic thrombolysis) is associated with improved long-term RV function. Materials and methodsRetrospective, single-center cohort study of adult (≥18 year old) patients admitted and discharged alive with a diagnosis of acute PE, who fell under the category of intermediate or high risk, with available follow-up echocardiograms at least 6 months after the index, seen at a single quaternary referral center in Los Angeles, CA between 2012 and 2021. ResultsThere were 113 patients in this study (58 (51.3 %) treated with anticoagulation alone, 12 (10.6 %) treated with systemic thrombolysis, and 43 (38.1 %) treated with catheter-directed intervention), with approximately equal gender and racial distribution. Patients treated with advanced therapies were significantly more likely to have moderate-severe RV dysfunction (100 % for those treated with thrombolysis, 88.3 % for those treated with catheter-directed intervention, vs 55.2 % for those treated with anticoagulation alone; p < 0.001). At a follow-up of about 1.5 years, patients treated with advanced therapy (systemic thrombolysis or catheter-directed intervention) were more likely to have normalization of RV function (93–100 % vs 81 % for anticoagulation alone, p = 0.04). The subgroup of patients with intermediate-risk PE was significantly more likely to have normalization of RV function (95.6 % vs 80.4 % for anticoagulation alone, p = 0.03). Use of advanced therapy was not associated with substantial short-term adverse events among patients who survived to hospital discharge. ConclusionPatients with intermediate and high risk PE were more likely to have recovery in RV function long-term if treated with catheter-directed intervention or systemic thrombolysis, as compared to anticoagulation alone, without substantial safety issues, despite having worse RV function at baseline. Further data is needed to verify this observation.

The Role of Transthoracic Echocardiography for Assessment of Mortality in Patients with Carcinoid Heart Disease Undergoing Valve Replacement

Patients with carcinoid heart disease (CHD) are referred for valve replacement if they have severe symptomatic disease or evidence of right ventricular (RV) failure and an anticipated survival of at least 12 months. Data are lacking, however, on the role of transthoracic echocardiography in predicting outcomes. We carried out a retrospective, single-centre cohort study of patients with a biopsy-confirmed neuroendocrine tumour (NET) and CHD undergoing valve replacement for severe valve disease and symptoms of right heart failure. The aim was to identify factors associated with postoperative mortality, both within one year of surgery and during long-term follow-up. Of 88 patients with NET, 49 were treated surgically (mean age: 64.4 ± 7.6 years; 55% male), of whom 48 had a bioprosthetic tricuspid valve replacement for severe tricuspid regurgitation; 39 patients had a pulmonary valve replacement. Over a median potential follow-up of 96 months (interquartile range: 56-125), there were 37 deaths, with 30-day and one-year mortality of 14% (n = 7) and 39% (n = 19), respectively. A significant relationship between RV size and one-year mortality was observed, with 57% of those with severe RV dilatation dying within a year of surgery, compared to 33% in those with normal RV size (p = 0.039). This difference remained significant in the time-to-event analysis of long-term survival (p = 0.008). RV size was found to reduce significantly with surgery (p < 0.001). Those with persisting RV dilatation (p = 0.007) or worse RV function (p = 0.001) on postoperative echocardiography had significantly shorter long-term survival. In this single-centre retrospective study of patients undergoing surgery for CHD, increasingly severe RV dilatation on preoperative echocardiography predicted adverse outcomes, yielding a doubling of the one-year mortality rate relative to normal RV size. These data support the possibility that early surgery might deliver greater long-term benefits in this patient cohort.

Right Ventricular Electromechanical Dyssynchrony and Its Relation to Right Ventricular Remodeling, Dysfunction, and Exercise Capacity in Ebstein Anomaly

Abnormal atrioventricular and intraventricular electrical conduction and dysfunction of the functional right ventricle (fRV) are common in Ebstein anomaly (EA). However, fRV mechanical dyssynchrony and its relation to fRV function are poorly characterized. We evaluated fRV mechanical dyssynchrony in EA patients in relation to fRV remodeling, dysfunction, and exercise intolerance. We retrospectively analyzed data from nonoperated EA patients and age-matched controls who underwent echocardiography, cardiovascular magnetic resonance imaging, and cardiopulmonary exercise testing to quantify right ventricular (RV) remodeling, dysfunction, and exercise capacity. The relation of these to fRV dyssynchrony was retrospectively investigated. Right ventricular mechanical dyssynchrony was defined by early fRV septal activation (right-sided septal flash), RV lateral wall prestretch/late contraction, postsystolic shortening, and intra-RV delay using two-dimensional strain echocardiography. The SD of time to peak shortening among the fRV segments was calculated as a parameter of mechanical dispersion. Thirty-five EA patients (10 of whom were <18years of age) and 35 age-matched controls were studied. Ebstein anomaly patients had worse RV function and increased intra-RV dyssynchrony versus controls. Nineteen of 35 (54%) EA patients had early septal activation with simultaneous stretch and consequent late activation and postsystolic shortening of RV lateral segments. Intra-fRV mechanical delay correlated with fRV end-diastolic volume index (r=0.43, P<.05) and fRV end-systolic volume index (r=0.63, P<.001). The fRV ejection fraction was lower in EA with versus without right-sided septal flash (44.9±11.0 vs 54.2±8.2, P=.012). The fRV mechanical dispersion correlated with the percentage of predicted peak VO2 (r=-0.35, P<.05). In EA, fRV mechanical dyssynchrony is associated with fRV remodeling, dysfunction, and impaired exercise capacity. Mechanical dyssynchrony as a therapeutic target in selected EA patients warrants further study.

303 IMPACT OF LEAD POSITION IN THE TRICUSPID ANULUS ON THE DEVELOPMENT OF CARDIAC IMPLANTABLE ELECTRONIC DEVICES RELATED TRICUSPID REGURGITATION

Abstract Introduction Originally considered as the “forgotten valve disease”, tricuspid regurgitation (TR) has recently been shown to correlate with consistent morbidity and mortality, suggesting the need for a deeper understanding of its natural course. Direct injury from Cardiac Implantable Electrical Device (CIED) leads is one of the most common causes of primary TR, with a prevalence up to 40%. The aim of the present proof-of-concept study was to evaluate the effect of CIED right ventricular (RV) lead position within the tricuspid anulus on TR development. Methods Consecutive patients undergoing CIED implantation at our institution (Humanitas Research Horpital IRCCS, Milan, Italy) were included, as long as they had been performed pre- and post- transthoracic echocardiogram (TTE) and a chest CT scan after the implantation. TTE and CT images were retrospectively reviewed. TR severity was graded using a pre-specified 4-class grading scheme: mild, moderate, severe and massive. CIED RV lead position was defined as postero-septal, antero-septal or antero-posterior, based on the commissure in which the lead was observed on a cross-sectional view of the tricuspid anulus at CT scan. Results 64 patients undergoing CIED implantation from January 2015 to December 2021 were included. All CT scans were non-ECG gated. TR was detected in 42 patients (65.62%) at pre-implantation TTE. The RV lead was implanted across the postero-septal, antero-posterior and antero-septal commissures in 35 (54.7%), 16 (25%) and 13 (20.3%) patients respectively. After the implantation, 12 individuals (18.75%) had new-onset or worsening TR, with CIED lead contributing to TR in 46.88% of cases (30/64), and 26 (40.63%) had worse RV function. At logistic regression analysis, the absence of atrial fibrillation was the only independent predictor of new-onset or worsening TR (OR: 0.17, 95% CI: 0.03-0.86, p=0.032), while CIED RV lead in the postero-septal commissure was associated with a numerically lower risk as compared to other sites (OR: 0.34, 95% CI: 0.09-1.27, p=0.108). Consistently, the degree of increase in TR severity was numerically lower in patients with a lead in the postero-septal commissure (Δ = 0.38±0.10 vs. 0.63±0.13, p=0.07). Conclusions CIED implantation is associated with increasing TR severity and worsening RV function. Positioning a lead across the postero-septal commissure of the tricuspid anulus might have a lower impact on TR development and worsening, thus representing a feasible option to prevent CIED-related TR.

Abstract 13266: Sex Specific Differences in the Gut Microbiome in Patients With Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) patients exhibit sexual dimorphism in pulmonary vascular remodeling and right ventricular (RV) dysfunction. While female PAH patients have severe pulmonary vascular remodeling, male PAH patients have worse RV function. Inflammation, a key component of PAH pathobiology, has been implicated as a potential mechanism for sexual dimorphism. Gut dysbiosis causes systemic inflammation. However, it is unknown whether gut dysbiosis contributes to sexual dimorphism in PAH. Hypothesis: There are sex-specific differences in the gut microbiome and microbial metabolites of PAH patients. Methods: 16S ribosomal ribonucleic acid gene sequencing was performed on stool samples from PAH patients (n=73). Markers of inflammation and circulating microbial metabolites were measured using plasma samples. Results: There was no significant difference in the Shannon diversity indices or species richness (Chao1 indices) between the gut microbiomes of male and female PAH patients. Moreover, principal component analysis of pairwise Bray-Curtis dissimilarity indices revealed no distinct microbiome compositions dependent on sex. There was no difference in serum claudin-3, a marker of gut permeability, and serum interleukin 6 levels between male and female PAH patients. When examining microbial metabolites, including trimethylamine N-oxide, short chain fatty acids, and secondary bile acids, no sex-specific differences were observed. Linear discriminant analysis of effect size revealed that there were no taxonomic differences based on sex. Conclusions: Male and female PAH patients do not possess distinct differences in their gut microbiomes or metabolites. There are also no sex-specific taxonomic differences. These findings do not support our hypothesis that gut dysbiosis may serve as a possible explanation for the sexual dimorphism observed in PAH.

Worsening Right Ventricular Function during Cardiac Surgery Is a Strong Predictor of Postoperative Acute Kidney Injury: A Prospective Observational Study.

This prospective, observational study was conducted in a university hospital to verify that intraoperative worsening of right ventricular function causes cardiac surgery-associated acute kidney injury. Adult patients undergoing cardiac surgery under mid-sternal incision with cardiopulmonary bypass were included. Echocardiographic right and left ventricular function parameters were measured before and after bypass and compared using the Wilcoxon signed-rank test. Perioperative serum creatinine values at baseline and within the first 48 hours postoperatively were measured for the diagnosis of acute kidney injury. Spearman rank-order correlation (ρ) and receiver operating characteristic analysis were used to reveal relationships. Thirty-four patients were evaluated. Right ventricular ejection fraction (56.2 ± 7.0 vs. 51.6 ± 7.2%; P = 0.0002), right ventricular fractional area change (49.1 ± 6.4 vs. 46.6 ± 5.3%; P = 0.0201; mean ± standard deviation), and left ventricular ejection fraction (57.4 ± 6.1 vs. 51.7 ± 6.2%; P < 0.0001) were significantly decreased. Central venous pressure was significantly increased (7.2 ± 3.5 vs. 9.7 ± 3.7; P = 0.0001). Serum creatinine values increased from 0.82 [0.70-1.08] to 0.99 [0.82-1.54] mg/dL (P < 0.0001; median [interquartile range]). Changes in right ventricular ejection fraction, fractional area change, and right ventricular strain during cardiovascular surgery were significantly correlated with changes in serum creatinine values. Fractional area change exhibited the strongest correlation (ρ = -0.61, P < 0.0001). Change in fractional area change showed an area under the curve of 0.902 and a cutoff value of -2.1, which predicted acute kidney injury with 92% sensitivity, 73% specificity, and 79% accuracy. The functions of both ventricles were decreased after cardiopulmonary bypass. Worsening right ventricular function was independently correlated with postoperative renal dysfunction, and fractional area change was the strongest predictor of cardiac surgery-associated acute kidney injury.

Prevalence and clinical impact of atrioventricular conduction disease in patients with idiopathic pulmonary arterial hypertension

Abstract Background Although bradycardia-related sudden death is common in patients with idiopathic pulmonary arterial hypertension (IPAH), the prevalence and prognostic significance of atrioventricular (AV) conduction disease in this patient group is not well-established. Objectives – Determine the prevalence of AV conduction disorders in patients with IPAH – Investigate the relationship between AV block and functional outcomes and mortality. Method 12-lead electrocardiograms (ECGs) of patients with IPAH were analysed. Patients were categorised according to the presence or absence of AV block. Demographic, pulmonary haemodynamic, cardiac structural characteristics and expression of genes associated with cardiac conduction were compared and functional and mortality outcomes analysed between groups. Student's t-tests and χ2 tests were used to compare data. Survival was estimated using Kaplan-Meier analyses. Initial exploratory covariates were included in a univariate analysis and those terms with P-value of &amp;lt;0.1 were then used to generate a Cox proportional-hazards multivariate model. Results 135 IPAH patients (mean age 55±16 years, 28.1% male) were eligible for analysis. Median follow up was 9 years (interquartile range 4–14 years). AV block was seen in 34.8% of patients with IPAH compared to 10.8% of matched comparators (p&amp;lt;0.001), drawn from patients attending hospital for non-PAH related reasons. IPAH patients with conduction disease were more likely to be older (59±16 vs 53±17 years, p=0.038). AV block was associated with more severe right ventricular (RV) basal dilatation (5.1±1.0 vs 4.3±0.7cm, p=0.013) and worse RV function (fractional area change 26±9% vs 31±9%, p=0.14). Pulmonary haemodynamics, right atrial size and resting and exertional oxygen saturations were not significantly different. Expression of HCN1, HCN2, SCN1B, SCN5A, CAV1, and KCN2 genes in peripheral blood from a subcohort was similar between those with and without AV block. Lower 6 minute walk distances (344±153 vs 408±140m, p=0.035) and worse CAMPHOR scores across all 3 domains were seen in those with AV block (figure 1), and mortality was significantly higher (36.2 vs 13.6%, p=0.002) (figure 2). On multivariate analysis the presence of bundle branch block (BBB) was independently associated with a 2.1-fold increased risk of death (95% CI 1.89–4.85, p=0.045). Conclusions AV conduction disorders are more prevalent in IPAH than the general population, and are associated with worse prognosis and functional status. Prospective study is required to validate this finding. In our cohort AV block could not be explained by hypoxia, differences in pulmonary haemodynamics nor, in a small subgroup, by differential expression of specific transmembrane ion channels implicated in cardiac conduction. More detailed investigation into causal mechanisms of AV block in IPAH could establish whether improved prognosis could be achieved by treatment of AV block. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

The right ventricular-pulmonary circulation coupling in ischaemic heart disease; a stress echocardiography study

Abstract Objectives This study sought to assess the right ventricular (RV) - pulmonary circulation coupling in patients with coronary artery disease (CAD), preserved echocardiographic indices of right ventricular systolic function and normal pulmonary artery systolic pressure (PASP). Background Patients with CAD are at increased risk for developing left, and ultimately right heart failure. The analysis of underlying mechanisms of worsening RV function has been limited to the hemodynamic sequelae of increased left ventricular (LV) filing pressure leading to pulmonary hypertension. It has been reported that evaluation of RV functional state by using the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a surrogate for the RV length-force is of clinical prognostic relevance in patients with known pulmonary hypertension; its role has not been extensively explored in other cardiac conditions including myocardial ischaemia. We hypothesized that the TAPSE/PASP ratio may be able to identify early and subtle changes in RV function in patients with CAD, normal estimated resting PASP, and preserved TAPSE. Methods Data were obtained from a prospectively maintained database, and 223 consecutive patients with preserved right ventricular systolic function (TAPSE≥16mm), and normal resting PASP (≤35mmHg), undergoing stress echocardiography (SE) for suspected coronary artery disease were included. Exclusion criteria: non-ischaemia study, severe valvular disease, poor image quality, resting pulmonary hypertension, reduced right ventricular systolic function. Transthoracic 2-D Doppler echocardiogram was performed by an accredited sonographer at rest and during stress phase and reviewed by two cardiologists unaware of clinical data. Results Fifty-three (24%) SE studies were positive for ischaemia and 170 (76%) negative. Demographic characteristics of both groups are shown in Table 1. All patients had TAPSE≥16mm and a PASP≤35mmHg as per inclusion criteria. The mean TAPSE/PASP ratio was significantly lower in patients with a positive SE suggestive of CAD than controls (0.84±0.22 vs 0.93±0.24, P=0.024). The TAPSE/PASP ratio showed significant correlation with the maximum workload (Watts) achieved (r=0.17, P=0.015) and exercise time (min) (r=0.15, P=0.031), and an inverse correlation with age (r=−0.26, P&amp;lt;0.001) and the development of inducible exertional breathlessness (Exp(B) 0.11, 95% CI 0.028–0.457, P=0.002) on SE. Conclusion Resting TAPSE/PASP was reduced in patients with positive SE, compared to controls. Indexing RV function to RV load, with the use of the TAPSE/PASP ratio identified early changes in RV-pulmonary circulation coupling in CAD patients without resting pulmonary hypertension; this may denote the beginning of subclinical RV dysfunction. Funding Acknowledgement Type of funding sources: None. Table 1

Evaluation of right ventricular function in acute pulmonary embolism by 3D ejection fraction and longitudinal strain echocardiography in acute phase and follow-up

Abstract Background Assessment of right ventricular (RV) function by transthoracic echocardiography (TTE) in acute pulmonary embolism (PE) has an essential role to severity stratification. However, there is no reliable information on RV function about the clinical utility of advanced TTE parameters in follow-up. Purpose We aimed to assess the clinical utility of 3D RV ejection fraction (3DEF) and free wall longitudinal strain (FWLS) compared to conventional parameters in evaluating RV function in patients with acute PE at time of diagnosis and after follow-up and the relation with adverse outcomes. Methods We prospectively recruited 86 patients with intermediate-high and high-risk bilateral PE from 2018 to 2020 in our centre. Patients underwent TTE during admission and at 6 to 12 months follow-up that included conventional RV parameters (pulsed Doppler S wave (S'), TAPSE, and fractional area change (FAC)). 3DEF and FWLS were obtained as well. Normal values were stablished according to European guidelines. Results Mean age was 63.7±16.5 years, 58% males. Reperfusion treatment was performed in a 26,8%. In-hospital mortality was 4,7% (3 patients in the acute phase of PE and 1 due to rePE. The median follow-up was 1.3 years (IQR 1–2.5). 9 patients died (2 due to PE, 3 due to respiratory failure and 5 due to cancer). Patients with adverse events had a greater severity in PESI scale and worse RV function assessed by 3DEF and 3D volumes. There were no significant differences between groups in FAC, S' and TAPSE (Table 1). Baseline echocardiographic parameters were analyzed in the acute phase during admission and at 6–12 month follow-up (Table 2). There was a significant improvement in conventional parameters (TAPSE and FAC) and a reversal of FWLS values (P=0,01) at follow-up. 3DEF improved, but was not statistically significant (p=0,06). There was a greater reversal in end-systolic volume compared to end-diastolic volume. Conclusion Advanced RV function assessment by 3DEF and FWLS is useful in the acute phase and follow-up. FWLS showed and early normalization after PE resolution, whereas 3DEF improved but remained pathological at 6–12 months follow-up. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation.

Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death. For patients who are hemodynamically unstable, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been shown to provide hemodynamic stability, and allow time for definitive treatment and recovery. Ultrasound-assisted catheter directed thrombolysis (USAT) has the potential to be a safe adjunct and expedite right ventricular (RV) recovery for patients requiring VA-ECMO for PE. A review of all VA-ECMO patients from January 2017 to September 2019 was performed. A total of 49 of these patients were cannulated due to a PE. USAT therapy was used as an adjunct in 6 (12%) of these patients. These 6 patients were given standardized USAT therapy with EKOs catheters at 1 mg/h of tissue plasminogen activator with an unfractionated heparin infusion for additional systemic anticoagulation. Outcomes, including in-hospital death, 90-day survival, RV recovery, and complications, were examined in the cohort of patients that received USAT as an adjunct to ECMO. Median age was 54 years old. Five of the six patients presented with a massive PE and had a PE severity score of Class V. One patient presented with a submassive PE with a Bova score of 2, but was cannulated to VA-ECMO in the setting of worsening RV function. All patients demonstrated recovery of RV function, were free from in-hospital death, and were alive at 90-day follow-up. Ekosonic endovascular system therapy may be a safe and feasible adjunct for patients on VA-ECMO for PE, and allow for survival with RV recovery with minimal complications.

Experimental design of the Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) trial.

Pulmonary arterial hypertension (PAH) remains life-limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin-1 (ET-1) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) is an on-going randomized double-blind placebo-controlled crossover trial of DHEA in men (n = 13) and pre- and post-menopausal women (n = 13) with Group 1 PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50 mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET-1 signaling, sex hormone levels, other PAH intermediate end points, side effects, and safety. The crossover design will elucidate sex-based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET-1 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study’s rationale and experimental design.

Bedside VA-ECMO Cannulation for a Patient with CTEPH and RV Failure

Introduction Acute pulmonary embolus (PE) in the setting of chronic thromboembolic pulmonary hypertension (CTEPH) with elevated PA pressures and right ventricular (RV) failure is a complex condition associated with increased mortality if left untreated. We demonstrate an alternative bedside veno-arterial extracorporeal membrane oxygenation (VA-ECMO) strategy used to facilitate stabilization and pre-operative optimization. Case Report A 29-year-old female with a history of previous PE (on Lovenox), RV dysfunction with elevated PA pressures, and IVC thrombus requiring VV-ECMO assisted suction embolectomy presented to an outside hospital with shortness of breath, hypoxia and CT demonstrating acute on chronic, bilateral PEs. A transthoracic echocardiogram (TTE) showed worsening RV function. She was normotensive, had a heart rate of 140, and was hypoxic so was placed on BiPAP. She was transferred to our facility for further management. On arrival, the patient was tachypneic and hypoxic. She was started on Epinephrine, Milrinone, and inhaled Epoprostenol but was persistently hypoxic with a rising lactic acid and worsening metabolic acidosis. With evidence of worsening RV failure, the patient was cannulated for VA-ECMO to facilitate optimization for advanced management. Prior to cannulation, bedside ultrasound revealed occlusive thrombus in both femoral and iliac veins. The venous drainage cannula was placed in the right internal jugular vein and the arterial return cannula was placed in the right common femoral artery, with antegrade reperfusion cannula. Bedside TTE was used to aide in cannula placement and cannula position was confirmed with x-ray.The patient was on VA-ECMO for 72 hours. During this time, her acidosis improved, Milrinone was weaned off, and she was diuresed. On ECMO day 3, she was taken to the OR for a pulmonary thromboendarterectomy and decannulated from VA-ECMO. The following day she was extubated and a TTE revealed improved right ventricular function. Summary Stabilization with VA-ECMO in patients with PE can be beneficial. This case illustrates the use of an alternative VA-ECMO cannulation strategy to optimize a patient with CTEPH. Of note, the cannulation occurred at the bedside with the use of ultrasound and without the need for intubation. Though this cannulation strategy is theoretically described in the literature, this case illustrates a concrete example of its use.

Echocardiographic Characteristics and Outcome in Patients With COVID-19 Infection and Underlying Cardiovascular Disease.

Background: The cardiac manifestations of coronavirus disease 2019 (COVID-19) patients with cardiovascular disease (CVD) remain unclear. We aimed to investigate the prognostic value of echocardiographic parameters in patients with COVID-19 infection and underlying CVD.Methods: One hundred fifty-seven consecutive hospitalized COVID-19 patients were enrolled. The left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography.Results: Eighty-nine of the 157 patients (56.7%) had underlying CVD. Compared with patients without CVD, those with CVD had a higher mortality (22.5 vs. 4.4%, p = 0.002) and experienced more clinical events including acute respiratory distress syndrome, acute heart injury, or deep vein thrombosis. CVD patients presented with poorer LV diastolic and RV systolic function compared to those without CVD. RV dysfunction (30.3%) was the most frequent, followed by LV diastolic dysfunction (9.0%) and LV systolic dysfunction (5.6%) in CVD patients. CVD patients with high-sensitivity troponin I (hs-TNI) elevation or requiring mechanical ventilation therapy demonstrated worsening RV function compared with those with normal hs-TNI or non-intubated patients, whereas LV systolic or diastolic function was similar. Impaired RV function was associated with elevated hs-TNI level. RV function and elevated hs-TNI level were independent predictors of higher mortality in COVID-19 patients with CVD.Conclusions: Patients with COVID-19 infection and underlying CVD displayed impaired LV diastolic and RV function, whereas LV systolic function was normal in most patients. Importantly, RV function parameters are predictive of higher mortality.

Abstract 16661: Fluid Challenge During Right Heart Catheterization for Evaluation of Pulmonary Hypertension Identifies Patients With Decreased Right Ventricular Function

Introduction: Fluid challenge during right heart catheterization (RHC) identifies occult left heart diastolic dysfunction (Occ-DD) in 10-20% of patients initially diagnosed with pre-capillary pulmonary hypertension (PH). The prognostic implications of the response to fluid challenge are not known. Abnormal right ventricular (RV) function is a poor prognostic indicator in all forms of PH. Hypothesis: We hypothesized that fluid challenge during RHC identifies patients with worse RV function and survival. Methods: Consecutive patients referred for RHC with fluid challenge from 2009-2016 were studied. Occ-DD was defined by a resting pulmonary arterial wedge pressure (PAWP) &lt; 15 mmHg, and a PAWP &gt; 18 mmHg after 500cc fluid challenge. Resting DD was defined by resting PAWP &gt; 15 mmHg. RV function was assessed by pulmonary artery pulsatility index (PAPi) or RV stroke work index (RVSWI). Statistical analysis was conducted using Kruskal Wallis test. Survival analysis was conducted by log rank test. Results: Of the 310 patients identified, 83% were female with a mean age of 54 + 14 years. The cohort consisted of 204 (66%) patients without DD, 30 (10%) with Occ-DD, and 76 (24%) with resting DD. Patients with Occ-DD were older (59 + 12 vs 51 + 14, p &lt; 0.0001) with greater BMI (31 + 6 vs 28 + 7, p &lt; 0.0001), but had similar prevalence of obesity, hypertension, diabetes mellitus, and coronary disease to all groups. Patients with Occ-DD had lower PAPi (7.8 + 0.4 vs 8.5 + 0.4, p &lt; 0.0001), lower RVSWI (9.9 + 0.8 vs 17.8 + 0.7 mmHg*ml/m2, p &lt; 0.0001) (Figure), and decreased survival (3.7 + 3.5 vs 4.9 + 3.5 years, p &lt; 0.0001) compared to those without DD. After adjustment for RV function, survival was no longer different between groups. Conclusions: Patients with Occ-DD after fluid challenge during RHC have decreased survival due to worse RV function compared to patients without DD. These findings suggest important prognostic implications for fluid challenge in the evaluation of patients with PH.

Right versus left heart reverse remodelling after treating ischaemic mitral and tricuspid regurgitation.

Repair outcomes of tricuspid regurgitation (TR) associated with ischaemic mitral regurgitation (IMR) are inferior to functional TR in terms of TR recurrence and right ventricular (RV) reverse remodelling. Our objective is to analyse right versus left heart reverse remodelling after surgery for IMR-associated TR. From 2001 to 2011, 568 patients with severe IMR underwent mitral valve surgery (repair 87%, replacement 13%), and 131 had concomitant tricuspid valve repair. Median follow-up was 3.0 years; 25% of living patients were followed up for 6.3 years. Longitudinal analysis of 1527 follow-up echocardiograms was performed to assess ventricular reverse remodelling and function. Unlike the left heart, the right heart failed to reverse remodel (failed to recover ventricular function or halt dilatation). During follow-up after surgery, the right ventricle continued to dilate while the left ventricle regressed in size. RV ejection fraction decreased (46% at 1 month and 44% at 5 years), while left ventricular ejection fraction increased (33% and 37%, respectively). RV strain showed early (-11% at 1 month) and late (-12% at 5 years) dysfunction. Patients who underwent tricuspid valve repair had worse RV function. Mitral regurgitation remained stable after surgical intervention, and TR gradually recurred (37% moderate, 20% severe at 7 years). Surgical treatment of IMR and TR along with revascularization failed to induce reverse remodelling of the right heart. These findings warrant further investigations to identify optimal timing and approach of intervention for IMR-associated TR with respect to RV remodelling.

Association between pre-operative right ventricular impairment on transthoracic echocardiography and outcomes after conventional and minimally invasive mitral valve surgery

Background Right ventricular (RV) impairment may have prognostic value in patients undergoing mitral valve surgery. It is unclear whether RV dysfunction predicts long-term mortality, especially in the era of minimally invasive mitral surgery. Methods We performed a retrospective analysis of consecutive patients referred for conventional (via sternotomy) and minimally invasive mitral valve surgery (MIMVS) between 01 January 2013 and 29 August 2018 in a tertiary cardiac centre. We truncated follow-up times at 25 March 2020. RV impairment was defined by reduced RV longitudinal function (TAPSE <17 mm) and/or dilated basal RV diameter (RVD1 > 42 mm). Primary outcome was all-cause mortality. Results The study cohort included 359 patients followed up for a median period of 4.2 (1.8) years. MIMVS approach was performed in 127 (35.4%) and conventional approach in 232 (64.6%) patients of whom 36 (28%) and 45 (19%), respectively, had RV impairment. EuroSCORE II was significantly higher in patients with RV impairment compared with patients with preserved RV function, irrespective of the surgical approach. Consequently, in both groups, patients with RV impairment had significantly higher mortality compared to patients with preserved RV function. RV impairment adjusted for EuroSCORE II predicted mortality in the whole cohort (HR 2.139, 95% CI 1.249–3.663) and in conventional approach (HR 2.361, 95% CI 1.249–4.465) in contrast to MIMVS (HR 1.570, 95% CI 0.493–4.997). Conclusion In this real world cohort, patients with RV impairment and/or dilation had reduced long-term survival following both conventional surgery and MIMVS. Patients should be referred to surgery prior to worsening of RV function.