Elevated Left Atrial Pressure Research Articles

Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction

Although the results of 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) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status. To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status. This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024. Atrial shunt device or sham control. Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure. The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, -5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, -2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs -1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading. In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed. ClinicalTrials.gov Identifier: NCT03088033.

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Pulmonary hypertension is an adverse risk factor for patients admitted with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) poses a significant burden on the resources of the American Healthcare system. Heart failure 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. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Since many who have AF could have PHT, we aimed to assess outcomes in this population. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 16,500,000 hospitalized adults who had AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those with AF, 1,855,020 (11.2%) had PHT. In-hospital mortality was higher in those with PHT (5.6% vs 4.9%; p&amp;lt;0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients with AF and PHT had longer length of stay (LOS) by 0.92 days (p&amp;lt;0.001) and had additional hospital costs (HC) of $9,463 (p&amp;lt;0.001). Conclusion In this study, patients admitted with AF with co-existing PHT had significantly worse outcomes in terms of in-hospital mortality, LOS, HC, cardiac arrest, pulmonary embolism, atrial flutter, AKI, blood transfusions, pneumonia, and endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Given that overall outcomes are worse in the setting of PHT, potential strategies for early rhythm control for AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.

Pulmonary hypertension is an adverse risk factor for peri-procedural complications in patients undergoing cardioversion for atrial fibrillation

Abstract Background Atrial Fibrillation (AF) poses a significant burden on the American Healthcare system. Heart failure 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. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Cardioversion (CV) for non-valvular atrial fibrillation (AF) is commonplace for patients during their initial presentation. Since many who undergo CV for AF could have PHT, we aimed to assess the periprocedural outcomes in this population. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 330,820 hospitalized adults who had CV for AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those who underwent CV for AF, 45,345 (13.7%) had PHT. In-hospital mortality was interestingly lower in those with PHT (9.6% vs 10.37%; p&amp;lt;0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients who underwent CV for AF and PHT had longer length of stay (LOS) by 2.11 days (p&amp;lt;0.001) and had additional hospital costs (HC) of $29,470 (p&amp;lt;0.001). Conclusion In this study, patients who underwent CV for AF with co-existing PHT had significantly worse outcomes in terms of LOS, HC, pulmonary embolism, atrial flutter, VT, SVT, AKI, and intubation. Of note, they interestingly had better outcomes in terms of in-hospital mortality, respiratory failure, and strokes. Returning the patient to sinus rhythm likely improved the left heart hemodynamics reducing post capillary pulmonary hypertension explaining the reduced mortality rate in this population. One major limitation of our study is the lack of outpatient follow up and the inability to differentiate between the different groups of PHT. Since several outcomes are worse in the setting of PHT, potential strategies for aggressive rate and volume control for those in AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.

Correlation between energy loss index and B-type natriuretic peptide: a vector flow mapping study.

Vector Flow Mapping (VFM) and Energy Loss (EL) evaluation are emerging echocardiographic techniques that offer detailed insights into cardiac function. This study aimed to explore the relationship between EL parameters and B-type natriuretic peptide (BNP) levels, a well-established marker of heart failure severity. Our study prospectively enrolled 62 patients experiencing shortness of breath and suspected heart failure, who underwent echocardiography and had BNP levels measured between January 2018 and August 2020. Patients were stratified based on BNP levels, and their clinical and echocardiographic characteristics were evaluated. Univariate and multivariate regression analyses were performed to assess the correlation between BNP levels and various echocardiographic variables, including VFM parameters. Patients were stratified into two groups based on their BNP levels: BNP < 200pg/ml (n = 53) and BNP ≥ 200pg/ml (n = 9). Patients with BNP ≥ 200pg/ml presented significantly different clinical and echocardiographic characteristics, such as older age, larger left ventricular mass and volume indices, higher pulmonary artery systolic pressure, higher E/e' ratio, and larger EL parameters. Multivariate regression analysis demonstrated the E/e' ratio and ELA (EL during Atrial contraction phase/A wave ratio as significant determinants of logBNP. Receiver operating characteristic curve analysis showed ELA/A > 36.0J/m2 as a significant predictor of high BNP with 89% sensitivity and 85% specificity. ELA/A demonstrated an incremental diagnostic value over elevated left atrial pressure for predicting high BNP (C statistic = 0.98 vs 0.74, P = 0.006). This study provides novel insights into the potential utility of EL parameters as auxiliary indicators of cardiac load, thereby enhancing our understanding of heart failure.

Prevalence, Associated Factors, and Echocardiographic Estimation of Left Atrial Hypertension in Patients With Atrial Fibrillation.

Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m2, P=0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, P=0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], P<0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all P<0.05), while LA volume and E/e' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. Conclusions Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.

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)