Elevated Left Atrial Pressure Research Articles

Prevalence of Heart Failure With Preserved Ejection Fraction in Patients Undergoing Atrial Fibrillation Ablation Based on Resting and Post-Tachycardia Pacing Left Atrial Pressure

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are frequent co-morbid conditions. In patients with symptomatic AF and preserved left ventricular ejection fraction the clinical diagnosis of HFpEF may be difficult, as history, examination, and echocardiography are not sensitive or specific. This study sought to assess the prevalence of HFpEF in patients undergoing AF ablation utilizing resting and post-tachycardia pacing left atrial pressure (LAP) measurements. This retrospective cohort study consisted of consecutive patients with symptomatic AF and preserved left ventricular ejection fraction who had invasive hemodynamic assessment (IHA) of LAP under resting and post-tachycardia pacing conditions while undergoing AF ablation from 2020 to 2022 at a tertiary care academic medical center. Elevated LAP was defined as ≥15 mm Hg at rest and ≥15 mm Hg post-tachycardia pacing. Patients were stratified into 3 groups: (1) normal resting and post-tachycardia pacing LAP (control group), (2) elevated resting LAP (apparent HFpEF), (3) normal resting but elevated post-tachycardia pacing LAP (occult HFpEF). A total of 78 patients were included with age 64.6 ± 9.1 years, 28 (36%) female, body mass index 33.3 ± 6.5 kg/m2, 5 (6%) paroxysmal and 73 (94%) persistent AF, and CHA2DS2-VASc 3.0 ± 1.5. IHA categorized 31 (40%), 32 (41%), and 15 patients (19%) into groups 1, 2, and 3 respectively. Notably, while only 9 patients (12%) were diagnosed with HFpEF based on clinical evaluation, 47 patients (60%) were diagnosed by IHA. IHA in patients undergoing AF ablation suggests a high prevalence of clinically undiagnosed HFpEF through a novel methodology measuring resting and post-tachycardia pacing LAP.

Predicting readmission for heart failure patients by echocardiographic assessment of elevated left atrial pressure

BackgroundPathophysiologically, an elevated left ventricular (LV) filling pressure is the major reason for heart failure (HF) readmission. The 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines provide a simplified algorithm for the echocardiographic assessment of LV filling pressure; however, this algorithm is yet to be sufficiently validated. Materials and MethodsWe retrospectively studied 139 consecutive patients with acute decompensated HF. High estimated left atrial pressure (eLAP) was defined according to the 2016 ASE/EACVI guidelines. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for HF readmission within one year of discharge. ResultsAcross the study cohort, 68 patients (49%) did not have a high eLAP, 32 (23%) had an indeterminate eLAP, and 39 (28%) had a high eLAP. The number of HF readmission events within one year in the without high eLAP, indeterminate, and high eLAP groups were 4 (7.5%), 5 (18.5%), and 10 (33.3%), respectively. The HF readmission rate was significantly higher in patients with high eLAP than in those without high eLAP. Multivariate analysis revealed high eLAP (odds ratio, 5.924; 95% confidence interval, 1.664–21.087; P = 0.006) as a significant risk factor for HF readmission within one year. Furthermore, the exploratory analysis of the two-year outcomes revealed a similar finding: patients with high eLAP had a significantly higher rate of readmission for HF. ConclusionsThe present study demonstrated that echocardiographic assessment of elevated LAP based on the 2016 ASE/EACVI guidelines is clinically valid for predicting readmission in patients with HF.

Validation of E/e′ Using the Index-Beat Method as an Estimate of Left Atrial Pressure in Patients with Atrial Fibrillation

Introduction: Echocardiographic assessment of diastolic function during atrial fibrillation (AF) remains challenging due to the irregular cardiac cycle length. We sought to assess whether the index-beat method, the beat following two preceding cardiac cycles of equal duration, could provide a more reliable measurement of E/e′ (mitral E wave/diastolic tissue Doppler velocity) than the conventional averaging of consecutive beats and hence facilitate the noninvasive estimation of elevated left atrial pressure (LAP) in patients with AF. Methods: We prospectively studied 35 patients with persistent AF who had preserved left ventricular ejection fraction and underwent radiofrequency ablation. LAP was measured in conjunction with transseptal puncture during catheter ablation. Echocardiography was performed 24 h before ablation and E/e′ was determined using the recommended averaging of 10 beats and the index-beat method, with the observers blinded to the clinical details and LAP measurements. Results: Correlation analysis showed a strong positive correlation between two methods in terms of both septal E/e′ (r = 0.841, p < 0.001) and lateral E/e′ (r = 0.930, p < 0.001). Bland-Altman analysis also showed a good agreement between the two measurement methods in terms of E/e′. E/e′ determined using both conventional averaging and the index-beat method was significantly correlated with LAP (p < 0.05). After Fisher Z transformation, we found that the index-beat septal E/e′ had a better correlation with LAP than did the conventional averaging E/e′ (r = 0.736 vs. r = 0.392, Zr = −2.110, p = 0.035). Furthermore, the index-beat method took significantly less time to measure E/e′ (mean 33.6 s; 95% confidence intervals [CIs]: 32.1 s–36.2 s) than did conventional averaging method (mean 96.2 s; 95% CI: 90.2 s–102.3 s; p < 0.001). Receiver operating characteristic curve analysis revealed that the optimal cut-off for predicting mean LAP >12 mm Hg was 11 (sensitivity 100%; specificity 77.3%) for index-beat septal E/e′ and 16 (sensitivity 61.5%; specificity 95.5%) for index-beat lateral E/e′. Conclusions: Good correlations were found between E/e′ and LAP in patients with AF, particularly with the index-beat method. Moreover, the index-beat method can easily measure E/e′ at an accuracy similar to that for the conventional averaging of consecutive beats, which can therefore be applied to assess the diastolic dysfunction and potentially improve the diagnosis of heart failure in patients with AF.

Impact of Estimated Left Atrial Pressure on Cardiac Resynchronization Therapy Outcome.

We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. Datasets of 219 CRT patients were retrospectively analysed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guideline algorithm into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and indeterminate LAP (iLAP = 11%). All relevant baseline characteristics were analysed. CRT-induced left ventricular (LV) reverse remodeling was measured as the relative change of LV end-systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Patients were followed up for all-cause mortality for a mean of 4.8 years [interquartile range (IQR): 2.7-6.0 years]. At follow-up, CRT resulted in more pronounced reduction of LVESV in patients with nLAP than in patients with eLAP. In univariate analysis, nLAP was associated with LV reverse remodelling (p < 0.001), as well as long-term survival after CRT (p < 0.01). However, multivariable analysis showed that only the association between nLAP and LV reverse remodelling after CRT is independent (p < 0.01). Adding LA strain analysis to the guideline algorithm improved the feasibility of LAP estimation without affecting the association between estimated LAP and CRT outcome. Normal LAP before CRT, estimated using the 2016 ASE/EACVI guideline algorithm, is associated with LV reverse remodelling and long-term survival after CRT. Albeit non-independent, it can serve as a non-invasive imaging-based predictor of effective therapy. Furthermore, the inclusion of LA reservoir strain in the guideline algorithm can enhance the feasibility of LAP estimation without affecting the association between LAP and CRT outcome.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction

BackgroundAtrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). ObjectivesThis study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. MethodsStudy investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. ResultsAmong 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. ConclusionsIn HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033)

The prognostic value of non-invasively estimated left atrial pressure in patients undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovative program under the Marie Sklodowska -Curie grant agreement No. 860745. Background The impact of non-invasively estimated left atrial pressure (LAP) on cardiac resynchronization therapy (CRT) outcome has been previously investigated, yet with inconsistent results. Aim We aim at investigating the association between baseline LAP and CRT outcome applying both the standard guideline approach (Nagueh et al 2016) and the integrated guideline + LA strain approach. Methods Datasets of 219 CRT patients were retrospectively analyzed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guidelines approach for estimation of LAP into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and undetermined LAP (uLAP = 11%, when classification was not possible due to missing data, Figure A, solid bars). All baseline characteristics, comorbidities, and ECG data in addition to LA strain components before CRT were collected and analyzed. The amount of CRT-induced LV reverse remodeling was assessed at 12±6 months after CRT and was defined as percentage decrease of LV end-systolic volume (LVESV) compared to baseline. Patients were followed up for a mean of 4.8 years (interquartile range (IQR): 2.7–6.0) for all-cause mortality. Results Compared to patients with eLAP, patients with nLAP were more of female sex (40% vs. 21%) and they had lower serum creatinine (1.1 ± 0.4 vs. 1.5 ± 0.6 mg/dl). ECG data showed that they had less prevalence of AF (9 vs. 15%). All LA strain indices were better in patients with nLAP (23 ± 9 vs. 12 ± 7% for reservoir strain, 10 ± 4 vs. 7 ± 5% for conduit strain and 11 ± 7 vs. 4 ± 4% for pump strain, P &amp;lt; 0.01 for all comparisons). At follow-up, LVESV was reduced more in patients with nLAP than in patients with eLAP (47 ± 28 vs. 30 ± 30%, P &amp;lt; 0.01, figure B solid bars). Survival rates of patients with nLAP was significantly higher than patients with eLAP (Hazard ratio (HR): 0.40; confidence interval (CI): 0.22–0.27; P &amp;lt; 0.01, figure C solid lines). In the subgroup of uLAP an LA reservoir strain was used to further identify patients with nLAP (LA reservoir strain ≥ 18%). Accordingly, the integrated guideline+LA strain approach improved the feasibility for classification from 89% to 97%, where the percentage of the uLAP dropped from 11% to 3% (only patients with no baseline LA strain remained classified as uLAP, figure A). Patients with nLAP according to the integrated approach showed very similar CRT-induced LV reverse remodeling (figure B dashed bars) and long-term survival as compared to patients with nLAP according to the standard approach (figure C dashed lines). Conclusion Applying the standard guideline approach for LAP, patients with nLAP before CRT show more LV reverse remodeling and better long-term survival after CRT, as compared to patients with eLAP. The guideline + LA strain approach markedly improves the feasibility of LAP estimation, while not influencing the association between LAP and outcome after CRT.

Diastolic dysfunction inhibits mechanical dyssynchrony in cardiac resynchronization therapy patients: a combined clinical-computational study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by the European Union's Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie grant agreement No. 860745. Background In heart failure patients treated with cardiac resynchronization therapy (CRT), both the presence of typical left bundle branch block (LBBB) mechanics and a relatively preserved diastolic function are associated with better clinical outcomes. However, the mechanistic interaction between both phenomena has never been investigated. Aim In this combined clinical-computational study, we explored the potential interaction between LBBB mechanics and the severity of diastolic dysfunction. Methods In 219 CRT candidates, left atrial pressure (LAP) was retrospectively estimated using the multiparametric guideline approach, where patients were classified into elevated (eLAP, 49%), normal (nLAP, 40%) and undetermined (uLAP, 11%) LAP. nLAP and uLAP were together referred to as non-elevated LAP (non-eLAP, 51%). Typical LBBB mechanical behavior was quantified using two speckle-tracking echocardiography-based indices, being systolic stretch index (SSI) and global myocardial wasted work (GWW). Both indices positively correlate with the mechanical interaction between septal and lateral walls in typical LBBB as previously shown. CRT response was quantified as change of LV end-systolic volume (LVESV) at follow-up (12±6 months) relative to baseline. We used the CircAdapt computer model of the human heart and circulation to investigate the effects of eccentric remodeling and diastolic dysfunction (i.e. myocardial stiffening) on SSI and GWW in virtual hearts with a constant LBBB-like septal-to-lateral conduction delay, i.e. a 25-ms and 75-ms mechanical activation delay of the septum and LV free wall with respect to the right ventricular free wall. Results Before CRT, patients with non-eLAP showed more typical LBBB mechanical behavior (Fig. 1), as suggested by higher SSI and higher GWW compared to patients with non-eLAP (SSI: 4.6±3.2 vs 3.4±3.5 %, P=0.02, GWW: 368±131 vs 309±127 mmHg*%, P=0.03). At follow-up, patients with eLAP showed significantly less LV reverse remodeling compared to patients with non-eLAP (relative decrease of LVESV: 30±26% vs 46±34 P=0.001). Our simulations (Fig. 2) revealed that eccentric remodeling amplifies mechanical dyssynchrony, characterized by increased septal rebound stretch (second row) and increased wasted work (third and bottom rows), while LAP remained normal (top row). In contrast, increasing myocardial stiffness led to elevated LAP (top row), but a pronounced reduction of mechanical dyssynchrony (second, third and bottom rows). Conclusion The presented combination of clinical data and virtual patient simulations revealed that diastolic dysfunction, in particular myocardial stiffening, inhibits mechanical dyssynchrony induced by LBBB. In contrast, eccentric remodeling amplifies the LBBB mechanical substrate. These data further explain why baseline dyssynchrony measures like septal rebound stretch and wasted work are well associated with reverse remodeling and clinical outcome after CRT.

Baseline mechanical dyssynchrony is associated with better diastolic function in patients undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovative program under the Marie Sklodowska -Curie grant agreement No. 860745. Background Outcome after cardiac resynchronization therapy has been shown to be worse in patients with diastolic dysfunction. Aim We aim at investigating the association between baseline mechanical dyssynchrony (Dyss) and diastolic function, both assessed using conventional 2D echocardiography in heart failure patients undergoing cardiac resynchronization therapy (CRT). Methods Datasets of 219 patients were retrospectively analyzed, including full echocardiographic diastolic function assessment before CRT implantation. Using the guideline approach (Nagueh et al 2016) for estimating left atrial pressure (LAP), patients were classified as elevated LAP (eLAP = 49%), normal LAP (nLAP = 40%), and undetermined LAP (uLAP = 11%). Patients with nLAP and uLAP together were referred to as non-elevated LAP (non-eLAP = 51%). Dyss was defined as the presence of apical rocking (ApRock) and /or septal flash (SF). All baseline characteristics, comorbidities, ECG data and left atrial (LA) strain components (reservoir, conduit, and pump strains) were collected and analyzed. The amount of CRT-induced LV reverse remodeling was assessed at 12±6 months after CRT and was defined as percentage decrease of LV end-systolic volume (LVESV) compared to baseline. Patients were followed up for a mean of 4.8 years (interquartile range (IQR): 2.7–6.0) for all-cause mortality. Results Compared to patients without Dyss, patients with Dyss were significantly more of female sex (39% vs. 14%), had less diabetes mellitus (21 vs. 34%), had lower serum creatinine (1.2±0.5 vs. 1.4±0.6 mg/dl) and less prevalence of ischemic cardiomyopathy, 43% vs. 68%). They used significantly more ACEi (91% vs. 76%). ECG data showed that they had less prevalence of AF (8 vs. 22%) and had wider QRS complex (158±18 vs. 152±18 msec), P-values &amp;lt;0.05 for all comparisons. Baseline LV volumes and EF were not significantly different between patients with and without Dyss. Patients with Dyss show less prevalence of eLAP compared to patients without Dyss (30% vs. 60%, P &amp;lt;0.001, figure A). Additionally, they had better LA function on all LA strain indices (Figure B). In the multivariable analysis for predicting the association with eLAP, the presence of Dyss was independently associated with less eLAP after adjusting for most of the baseline variables (HR: 0.31, CI: 0.1–0.7, P &amp;lt;0.01). At follow up, patients who had both Dyss and non-eLAP before CRT showed the largest amount of LV reverse remodeling compared to other patients. Similarly, the patients with Dyss and non-eLAP showed the best survival compared to other groups (figure C). Conclusion The presence of mechanical dyssynchrony is associated with better diastolic function and lower estimated LAP before CRT. Additionally, the combination of Dyss and non-eLAP before CRT was associated with the most CRT-induced LV reverse remodeling and best long-term survival.

P73: Subclavian Artery Cannulation For Left Ventricular Unloading During Extracorporeal Membrane Oxygenation Support

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective mechanical circulatory support for cardiac insufficiency following cardiac surgery especially cardiac surgery with extracorporeal circulation, which can quickly restore the perfusion of vital organs. However, retrograde blood flow in the aorta during VA-ECMO may lead to increased left ventricular (LV) afterload, elevated LV filling pressure, mitral insufficiency, and elevated left atrial pressure, which may subsequently result in reduced coronary blood flow and pulmonary edema, thus aggravating the patient’s condition. Therefore, LV unloading is necessary during VA-ECMO. The optimal approach for LV unloading remains undefined, but the percutaneous access has been increasingly used over time. To addresss this issue, we have attempted to use cannulation of the subclavian artery for left ventricular unloading during VA-ECMO. This study aims to describe our method and report the preliminary results in three patients. Methods: Three patients with low cardiac output syndrome after cardiac surgery. All 3 patients had difficulty weaning from cardiopulmonary bypass (CPB) due to overfilling and contractile weakness of the heart, low mean arterial pressure<80mmHg, and left atrial pressure of >20 mmHg. Decision was made to start ECMO support immediately, and LV unloading was initiated via cannulation of the subclavian artery (Table 1). Given the differences in the surgical approaches and condition of patients, three methods were used to achieve LV unloading via the subclavian artery.Methods of LV unloading with cannulation via the subclavian artery during VA-ECMO in three patients with low cardiac output syndrome after cardiac surgery: 1) VA-ECMO with LV unloading via subclavian artery; 2) femoral vein-to-subclavian artery VA-ECMO with LV unloading via a 4-branched graft; 3) LV bypass via femoral artery-subclavian artery. Results: In all patients, the subclavian artery cannula was withdrawn at postoperative days 2-3, and ECMO was successfully weaned on postoperative day 4. One patient developed cardiac tamponade within 24 hour of surgery, echocardiography showed an LVEF of 55%. During an exploratory thoracotomy, a large amount of blood clot about 500 mL was found in the pericardium and removed, and the patient recovered uneventfully. Table 2 summarizes the postoperative courses of the 3 patients with different LV unloading methods. Conclusion: This study partly illustrated that LV drainage via the subclavian artery could safely and effectively reduce the LV load, prevent VA-ECMO-related complications, and minimize the risk of trauma and infection during LV examinations. Certainly, whether the subclavian artery approach is the optimal strategy for LV unloading as well as patient risks and benefits remains to be further investigated.Figure 1. ECMO + LV unloading schematic diagram of Case 1 (femoral artery + femoral vein+ subclavian artery)Figure 2. ECMO + LV unloading schematic diagram of Case 2 (femoral artery + femoral vein + four branches aortic graft)Figure 3. LV unloading schematic diagram of Case 2 (femoral artery + subclavian artery)

Deep learning approach for analyzing chest x-rays to predict cardiac events in heart failure.

A deep learning (DL) model based on a chest x-ray was reported to predict elevated pulmonary artery wedge pressure (PAWP) as heart failure (HF). The aim of this study was to (1) investigate the role of probability of elevated PAWP for the prediction of clinical outcomes in association with other parameters, and (2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF. We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP. Readmission following HF and cardiac mortality were the primary endpoints. Probability of elevated PAWP was associated with diastolic function by echocardiography. During a median follow-up period of 58 months, 57 individuals either died or were readmitted. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge was associated with event free survival, independent of elevated left atrial pressure (LAP) based on echocardiographic guidelines (p < 0.001). In sequential Cox models, a model based on clinical data was improved by elevated LAP (p = 0.005), and increased further by probability of elevated PAWP (p < 0.001). In contrast, the addition of pulmonary congestion interpreted by a doctor did not statistically improve the ability of a model containing clinical variables (compared p = 0.086). This study showed the potential of using a DL model on a chest x-ray to predict PAWP and its ability to add prognostic information to other conventional clinical prognostic factors in HF. The results may help to enhance the accuracy of prediction models used to evaluate the risk of clinical outcomes in HF, potentially resulting in more informed clinical decision-making and better care for patients.

PO-05-204 MULTI-CENTER CLINICAL OUTCOMES OF A NO-IMPLANT INTERATRIAL SHUNT FOR HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION: UPDATE FROM THE EARLY FEASIBILITY ALLEVIATE-HF PROGRAM

Chronic heart failure (HFpEF and HFrEF) remains an important area of unmet need despite current best medical therapies available. Implantable interatrial shunt devices may improve quality of life and functional capacity with favorable safety signals but require permanent implantation to maintain patency. We report the 6-month clinical outcomes of a no-implant approach to interatrial shunting across three studies: ALLEVIATE-HF-1 and ALLEVIATE-HF-2 for HFpEF, and a dedicated HFrEF study. Patients aged ≥ 40 years, NYHA class II, III or ambulatory IV and elevated left atrial pressure (PCWP) during supine ergometry were included in the studies. Baseline assessments included echocardiography, exercise right heart catheterization, KCCQ and 6MWT. Femoral venous access and standard transseptal catheterization techniques were employed. The device was utilized to excise a segment of the interatrial septum using a pulse of radiofrequency energy to create a shunt under fluoroscopic and echocardiographic guidance. A total of 28 HFpEF and 5 HFrEF patients were enrolled. Mean LVEF was 60 ± 8% and 30 ± 8% in HFpEF and HFrEF patients, respectively. Procedures were successful with no device or procedure-related adverse events. Six-month outcomes are reported in the table. TTE and CT confirmed all shunts assessed maintained patency (n=30). No device or procedure-related serious adverse events occurred upon discharge and through 6 months. This early feasibility clinical experience demonstrates procedural safety and feasibility of the Alleviant no-implant interatrial shunt creation with a promising efficacy signal through 6 months in patients with HFpEF and HFrEF. Enrollment for the forthcoming randomized sham-controlled pivotal study (ALLAY-HF) is anticipated to begin early 2023.

Unrecognized Patent Foramen Ovale in Patient With Sinus Venosus-Type Atrial Septal Defect With Partial Anomalous Pulmonary Venous Return.

Unrecognized Patent Foramen Ovale in Patient With Sinus Venosus-Type Atrial Septal Defect With Partial Anomalous Pulmonary Venous Return.

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

BackgroundMany patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. ObjectivesThis study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). MethodsThe REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). ResultsPatients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e′, and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. ConclusionsPatients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033)

Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction.

Elevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF. Data from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index-based tertiles (≤34 ml/m2 , >34 to ≤45 ml/m2 , >45 ml/m2 ). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n=60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (padjusted <0.001), higher resting mean pulmonary artery pressure (padjusted =0.003), with similar wedge pressure (padjusted =1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (padjusted <0.001). Larger LA volumes featured reduced LA strain (padjusted <0.001), with reduced strain associated with reduced PVR-compliance time (0.34 [0.28-0.40] vs. 0.38 [0.33-0.43], p=0.03). Increasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR-compliance relationship, further augmenting impaired pulmonary haemodynamics.

931 EVALUATION OF IATROGENIC ATRIAL SEPTAL DEFECT CLOSURE AFTER TEER

Abstract Iatrogenic atrial septal defect (iASD) represents one of the main access-related cardiac complications after trancatheter edge to edge (TEER) mitral valve repair with Mitraclip system. Transesophageal echocardiography (TEE) guiding supports a controlled and safe transseptal puncture. The rate of persistent iASD is 57, 50, and 25% after 1, 6, and 12 months post procedure. An elevated left atrial pressure after clip positioning correlates with iASD persistence. Its clinical impact is controversially discussed: Post-TEER iASD has been associated with right heart volume overload, as well as increased rates of heart failure (HF) hospitalization and death in some studies. In contrast, other studies have shown an association between post-TEER iASD and improved hemodynamics. In theory, creation of an iASD can decompress an overloaded left atrium, mitigating heart failure. Some studies have demonstrated that iASD closure can reduce significantly both right and left heart failure symptoms. We did a retrospective study enrolling in the period 2012-2022 twenty-one patients with severe mitral regurgitation treated with TEER. Our aim was to evaluate the clinical outcomes (symptoms, signs of heart failure, NYHA functional class) and echocardiographic parameters (PAPs, TAPSE, Right Atrium Area) in two group of patients: Group A underwent iASD closure during the TEER and Group B after one month following the TEER. At 1-month follow-up all patients with repaired mitral regurgitation showed an improvement in the NYHA class (from IV-III to II-I) and no need for re-hospitalization with no significant differences between two groups. In the Group A there were two adverse events during the recovery (2 major bleeding); while there were no adverse events in patients undergoing iASD closure after wise. There was 1 death in the first month after the procedure in group A, while there wasn't any in group B. Statistical analysis showed no significant differences in terms of NYHA class improvement in the two groups (p=0.91). We observed a greater reduction in PAPs in patients going to encounter intraprocedural DIA closure which was found to be statistically significant (p=0.01). Regarding TAPSE, there was a difference in terms of improvement which was found to be greater in the group A. However, this finding was not found to be statistically significant. We also assessed the right atrium area: in group A, we registered a mean preprocedural value of 28 cmq and a postprocedural value of 34 cmq; in group B the values were 20 cmq and 24 cmq, respectively, with a nonstatistically significant difference in terms of atrial enlargement post device placement. In conclusion, we can assume that the improvements in symptomatology are not closely related to iASD closure. However, it must considered that patients in group A had more unfavorable echocardiographic values before the procedure than those in group B, and probably, if we had not closed the iASD immediately during the procedure, these patients would have had worse symptomatology. Therefore, targeted patient selection is essential.

1109 PULMONARY PRESSUR TREND ANALYSIS IN PATIENTS UNDERGOING MITRACLIP

Abstract Mitral regurgitation (MR) is the second most frequent valve heart disease in Europe and its underlying mechanism primary-organic (due to disease of the mitral leaflets), or secondary-functional (where valve leaflets and chordae are structurally normal and MR results from alterations in left ventricle and left atrium geometry), determines the therapeutic approach. Transcatheter Edge-to-Edge Repair (TEER) with MitraClip implantation is a minimal-invasive treatment that according to 2021 ESC Guidelines should be considered (class of recomandation IIa) in selected symptomatic patients with severe MR despite optimal medical therapy, not eligible for surgery and fulfilling COAPT trial inclusion criteria, suggesting an increased chance of responding to treatment. Optimal valve morphology features for TEER are central pathology (second scallop), no leaflet calcifications, mitral valve area &amp;gt;4cm2, mobile length of posterior leaftel &amp;gt;10 mm, coaptation depth &amp;lt;11mm, normal leaflet strength and mobility, flail width &amp;lt;15 mm, flail gap &amp;lt;10 mm. TEER may be considered (class IIb) only in selected cases when the COAPT criteria are not fulfilled with the aim of improving symptoms and quality of life. MR occurs during systole, that at normal heart rates represents 30-50% of the cardiac cycle. As such, marked left atrial (LA) pressure elevation is present only transiently, representing less of a drive to development of secondary pulmonary hypertension compared to chronic LA pressure elevation seen in severe mitral stenosis. Anyway, in patients with severe MR echocardiography often reveals elevated systolic pulmonary artery pressure (PAPs) and MitraClip implantation usually is associated with a slight increase of the trans-mitral gradient with possible repercussions on pulmonary pressures. To better describe the effect of MitraClip implantation on pulmonary pressures and clinical outcomes we did a retrospective study enrolling in the period 2012-2022 thirty-six patients with severe mitral regurgitation treated with TEER. Compared to the last year presentation, we add eleven patients. The target was still to evaluate the clinical outcomes (symptoms, signs of heart failure, NYHA functional class) and the pulmonary pressures assessed by an echocardiographic examination before and after the intervention. At 6-month follow-up we observed in all patients with repaired mitral regurgitation an improvement in the NYHA class (from IV to II) without re-hospitalization. In addition we notice a more pronounced trend in the reduction of the mean sistolic pulmonary arterial pressure, estimated at around 2.86 mmHg ± 14 mmHg (p 0.24, 95% C.I. -7.69 to 1.94) with an unchanged left ventricle ejection fraction. Moreover, the echocardiographic exam showed a normalization of the S and D waves pattern in the pulmonary veins at the PW Doppler evaluation. These new data reinforced the idea that the clinical improvement and the reduction of dyspnea in these patients underwent TEER is related to a reduction of pressures in the pulmonary circulation regardless of the ejection fraction. This finding could be used as a tool that the cardiologist has to evaluate in the echocardiography lab to reveal a new mitral valve disfunction. Despite the addition of the new patients, the sample is still relatively small. However, considering the improvement of the results with the enlargement of the sample, the goal is to enroll additional patients to make the study even more meaningful.

Abstract 14409: Deep Learning Approach for Analyzing Chest X-rays to Predict Cardiac Events in Heart Failure

Introduction: A deep learning (DL) model based on a chest X-ray (CXR) was reported to predict elevated pulmonary artery wedge pressure (PAWP) as congestive heart failure (HF). Hypothesis: We hypothesize that a previously developed application of a CXR-based DL algorithm could also be used to predict re-hospitalized HF in patients with HF. This study aimed to 1) investigate the role of probability of elevated PAWP to predict clinical outcomes in association with other parameters, and 2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF. Methods: We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP in the study cohort. The primary endpoint was readmission following HF and cardiac death. Results: Probability of elevated PAWP was associated with echocardiographic parameters including left atrial size, filling pressure, and pulmonary artery pressure. During a median follow-up period of 58 months, 57 patients were either readmitted or died. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge (per 1SD) was associated with event free survival, independent of elevated left atrial pressure (LAP) by echocardiography (hazard ratio:1.39, 95%CI:1.17-1.65, p&lt;0.001). In sequential Cox models, a model based on clinical data (χ2, 16.8) was improved by elevated LAP (χ2,24.4; p =0.005), and increased further by probability of elevated PAWP (χ2,41.1; p &lt;0.001). Conclusions: This study suggests that probability of elevated PAWP provides important incremental prognostic value for predicting readmission and cardiac mortality risk assessment in patients with HF.

Abstract 15442: Pharmacological and Atrial Cardiomyocyte-Specific Inhibition of Tumor Necrosis Factor (TNF) Protects Against Adverse Atrial Remodeling and Valvular Atrial Fibrillation an a Mouse Model of Aortic Regurgitation

Introduction: Atrial fibrillation (AF) is the most common sustained supraventricular arrhythmia worldwide. Most conditions linked to AF, such as cardiovascular (CVD) and valvular disease, are linked to elevated atrial pressures and atrial cardiomyocyte (CM) stretch, which are powerful stimuli for atrial remodeling. We have shown that the proinflammatory and mechanosensitive cytokine tumor necrosis factor (TNF) is a key mediator of stretch-related atrial remodeling and AF. Hypothesis: As TNF is a critical factor mediating fibrosis, hypertrophy, inflammation, and arrhythmias in CVD, we hypothesized that targeting TNF-dependent signaling may offer a novel therapeutic target in AF patients. Methods: We created an aortic regurgitation (AR) mouse model of volume overload characterized by elevated left ventricular end diastolic (LVEDPs) and atrial pressures. To examine TNF-dependent AF pathogenesis in AR, the impact of Tnf excision in atrial CMs (Cre-recombinase expression controlled by an Nppa promoter) and pharmacological TNF inhibition with Etanercept (twice-weekly, 2.5 mg/kg) beginning 2-days (early) or 1-week (delayed) post-AR in CD1 mice were examined. Cardiac structural, functional, and electrophysiological properties were assessed using echo, pressure telemetry, immunohistochemistry, in vivo intracardiacs, and ex vivo optical mapping of AF. Results: Four weeks of AR resulted in chronically elevated LVEDPs and progressive LV dilatation, functional impairment, and hypertrophy in the absence of ventricular arrhythmias with or without TNF inhibition compared to SHAM mice. In atria, AR resulted in both in vivo (8/11, 73%) and ex vivo (5/8, 63%) AF inducibility, which was associated with hypertrophy, fibrosis, and macrophage infiltration (F4/80 + ) as well as decreased conduction velocity and atrial effective refractory periods. Importantly, atrial CM-specific Tnf excision (n=10) and both early (n=8) and delayed (n=6) pharmacological TNF inhibition attenuated AR-induced adverse atrial remodeling and protected against AF inducibility. Conclusions: AF pathogenesis and vulnerability with AR requires TNF, suggesting TNF is an important therapeutic target for the prevention and treatment of AF linked to elevated atrial pressures.

Abstract 15329: Heart Failure is an Adverse Risk Factor for Peri-Procedural Complications in Patients Undergoing Pulmonary Vein Isolation and Ablation for Atrial Fibrillation

Introduction: Percutaneous catheter ablation (PCA) for non-valvular atrial fibrillation (AF) is rapidly becoming commonplace for recently diagnosed paroxysmal AF. Heart failure (HF) and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Since many who undergo PCA for AF could have HF, we aimed to assess peri-procedural outcomes in this population. Methods: We utilized the National Inpatient Sample from 2016-2019 to identify 74,205 hospitalized adults who underwent PCA for AF. These hospitalizations were further stratified based on the presence of HF. A multivariate regression model was used to adjust for confounders and analyze the variables. Results: Of those who underwent PCA for AF, 33,435 (45%) had HF. In-hospital mortality was higher in those with HF (1.9% vs 1.14%; p=0.0001). Figure 1 shows the Forrest plot for multivariate analysis of peri-procedural complications when adjusted for patient demographics, co-morbidities, and hospital characteristics. When adjusted similarly, patients with HF who underwent PCA for AF had longer length of stay (LOS) by 1.5 days (p&lt;0.001) and had additional hospital costs (HC) of $14,726 (p&lt;0.001). Conclusions: In this study, patients undergoing Percutaneous catheter ablation (PCA) for AF with co-existing acute HF had significantly worse end points in terms of in-hospital mortality, LOS, HC, atrial flutter, AKI, sepsis, pneumonia, endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Although outcomes are worse in the acute setting of HF, there have been several studies such as CASTLE-AF, outlining that early ablation for AF in HF is associated with positive long-term effects including lower rates of death and hospitalization for HF. Despite unfavorable peri-procedural outcomes of HF in PCA, the long-term benefits should not be overlooked.