Endpoint Of Heart Failure Hospitalization Research Articles

Characteristics and outcomes of patients with a history of cancer enrolled in our prospective HFpEF registry

Abstract Background Along with the aging population, the incidence of concomitant heart failure with preserved ejection fraction (HFpEF) and cancer, is increasing. However, little is known about the typical characteristics of patients with both HFpEF and a history of oncologic disease. Aim We aimed to characterize the distinctive characteristics and outcomes of patients with a history of cancer within a prospective HFpEF registry. Methods We analyzed data from 491 unselected HFpEF patients from our tertiary university center between 2010 and 2022 and followed the patients until 2023. Laboratory parameters and comorbidities were assessed. Patients were categorized into those with and without a history of cancer, including various malignancies, survivors of childhood cancer, radiation therapy, with or without chemotherapy. Kaplan-Meier estimates were used to explore the association between cancer history, as well as previous radiotherapy, and a combined endpoint of heart failure hospitalization and/or all-cause death. Results In this analysis of 491 HFpEF patients, a total of 101 patients (21%); had a history of cancer [mean age 74±7 years; female 72 (72%), male 29 (29%)]. The median time from cancer diagnosis to the initial HFpEF visit was 7.0 years (IQR 13-0.5 years). The most prevalent primary cancer sites included the chest wall (32%) comprising 4 adenocarcinomas of the lung and 28 cases of breast cancer, followed by the gastric (28%), urogenital system (18%), hematologic and lymphatic system (16%), cancers located at the head and neck (5%) and endocrine malignancies (1%). Radiotherapy (39%) and chemotherapy (26%) were common. Notably, no significant differences were observed, between patients with or without a history of cancer, in terms of median NT-proBNP levels [1037 (IQR 416-2075) vs. 1060 pg/ml (IQR 462-2013)] and the frequency of key cardiovascular comorbidities (all p>0.05, see Table 1). Over the study period [median follow-up 50 months (IQR 18-76)], 64 (64%) of cancer patients met the combined endpoint, with no statistically significant difference in outcomes between HFpEF patients with and without a cancer history (log-rank p=0.222, see Figure 1). Furthermore, there was no significant difference in the combined endpoint between patients who had undergone radiotherapy and those without (log-rank p=0.162). Conclusion Our findings highlight a high coexistence of cancer and HFpEF, which can frequently occur after oncology therapies. The data suggest that the presence of a history of cancer or previous radiotherapy did not significantly impact overall outcomes in HFpEF patients compared to those without cancer during the study period. Further research is needed to characterize patients with both disease entities in detail. Due to modern cardiovascular therapy in a university and cardio-oncology clinic setting, outcomes for cancer patients appear better than expected.

New joint model for the dynamic prediction of heart failure in phospholamban (PLN) p.(Arg14del) positive individuals

Abstract Background PLN p.(Arg14del) positive individuals are at risk for developing arrhythmogenic cardiomyopathy which can cause severe heart failure. Future gene therapy could be lifesaving and is rapidly advancing. It is therefore of importance to identify eligible patients for this evolving treatment, with individuals risk prediction playing an imperative role in this process. Purpose To develop a dynamic prediction model for the individual risk prediction of heart failure in PLN p.(Arg14del) positive individuals. Method Data were collected of 564 PLN p.(Arg14del) positive individuals with no baseline history of heart failure or myocardial infarction. During a median follow-up of 6.3 years (interquartile range 2.9-10.0), 74 individuals experienced heart failure, defined as a composite endpoint of heart failure hospitalization, left ventricle assist device implantation, heart transplantation and heart failure-related death. For the individual prediction of time to heart failure we used a joint model which simultaneously estimates a longitudinal model for repeatedly measured left ventricle ejection fraction (LVEF) during follow-up and a Cox regression model for the hazards of the heart failure endpoint. Using the longitudinal model we predicted the LVEF-values of all patients at future time points using the estimated random-effects and these predicted LVEF values were used as a time-dependent covariate in the Cox model which also contained age at start of follow-up as predictor variable. Results The joint model trained in this study had a very good performance in discriminating the individuals at risk for heart failure, with the 5-year mean AUC of 0.86 and 10-year mean AUC of 0.84. The LVEF had a hazard ratio of 0.89 (95% confidence interval (CI) 0.86-0.93, p<0.001), and age at baseline 1.04 (95% CI 1.03-1.06], p<0.001), meaning a lower LVEF and higher age at presentation were associated with heart failure. Figure 1 shows an example of an individual risk prediction with on the x-axis the follow-up time in years, on the y-axis (left) the LVEF in % and on the y-axis (right) the predicted survival probability. Conclusion Individual risk prediction with a simple model including only LVEF and age is of great importance for identifying PLN p.(Arg14del) positive individuals who are at risk of developing heart failure. The introduction of this novel joint prediction model is the first step in identifying individuals at risk for heart failure and may aid patient selection for future gene therapy interventions.

Impact of right ventricular to pulmonary artery coupling on remodeling and outcome in patients undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Right ventricular to pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce. Methods Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed using a composite endpoint of heart failure hospitalization and death. Results Between April 2018 to January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio <0.36. Event-free survival rates at 2 years were significantly lower among patients with impaired coupling (57 vs. 82%, p<0.01), both in patients with primary (64 vs. 91%, p=0.01) and secondary MR (54 vs. 76%, p=0.03). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio <0.36 was independently associated with outcome (adj.HR 2.74, 95%CI: 1.17-6.43, p=0.02). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ +3mm, PASP: ∆ -10mmHg, p for both <0.01), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥II: 77 to 54%, p<0.01). Conclusion TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome.Graphical Abstract

Right ventricular global longitudinal strain on cardiovascular magnetic resonance imaging predicts outcome in patients undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Right ventricular dysfunction (RVD) on echocardiography was shown to predict outcomes in patients undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, the prognostic value of left and RV global longitudinal strain (LV- and RV-GLS) on cardiovascular magnetic resonance feature tracking (CMR-FT) is unknown. Methods Consecutive M-TEER patients underwent pre-procedural and follow-up CMR-FT analysis. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization (HFH) and death. Results 62 patients (78.3±7.0y/o, 45% female, EuroSCORE-II: 9.6±7.1%) underwent CMR-FT prior to M-TEER, 24% had concomitant tricuspid edge-to-edge repair (T-TEER). On presentation, 23 (37%) patients suffered RVD, defined as RV-GLS >-20% on CMR-FT. RVD was associated with reduced LV and RV ejection fraction (LVEF: 39 vs. 49%, p=0.01, RVEF: 35 vs. 47%, p<0.01), as well as impaired LV-GLS (-14.0 vs. -19.5%, p=0.01). Eighteen events (12 deaths, 6 HFH) occurred during follow-up (11.4±9.1months). On multivariable Cox-regression adjusted for baseline, procedural, imaging, and biomarker data, RV but not LV-GLS was significantly associated with outcome (adj.HR 2.50, 95% CI: 1.29-4.86, p=0.01 and 1.46, 95% CI: 0.50-4.28, p=0.49, respectively). Among various definitions of RVD on echocardiography and CMR, only RV-GLS on CMR-FT was significantly associated with outcome (RV-GLS >-20%: adj.HR 7.53, 95% CI: 2.07-27.42, p<0.01), but not RVEF on CMR or echo-indices of RV function. Follow-up CMR-FT was performed in 21 (34%) patients and RV-GLS significantly improved after TMVR (-20.6 to -25.2%, p=0.02), irrespective of additional T-TEER. Conclusions RV-GLS, as determined on CMR-FT, rather than LV-GLS or RVEF, is an independent predictor of outcome in patients undergoing M-TEER.Central Illustration

The impact of outpatient pharmacological optimization on echocardiographic parameters in heart failure with reduced ejection fraction

Abstract Background The 2022 landmark STRONG-HF study demonstrated that aggressive uptitration of guideline directed medical therapy (GDMT) in patients recently hospitalized for heart failure leads to a reduction in the composite endpoint of heart failure hospitalization and mortality. However, the impact of optimization of GDMT on echocardiographic parameters in heart failure with reduced ejection fraction (HFrEF) is unknown. Purpose This goal of this study was to determine the impact of a virtual HFrEF optimization program for achieving GDMT uptake and its impacts of echocardiographic parameters. Methods We conducted a single center study at a Canadian community cardiovascular centre using a prospective pre-post design. NYHA class II/III HFrEF patients referred from inpatient and outpatient settings were enrolled in our virtual 3-month HFrEF optimization program. All participants underwent an initial consult with a nurse and cardiologist. After this, all patients were seen remotely by a nurse every two weeks for adjustment of HFrEF medications with the goal of maximally tolerated GDMT dosing within 3 months was. Transthoracic echocardiograms were performed prior to participation in the program & after completion. Results Over 9 months, 284 NYHA class II/III HFrEF patients enrolled in the virtual HFrEF optimization program. Mean age was 67 and 70% were male. Mean ejection fraction was 34% and 54% had New York Heart Association Class II symptoms. At intake, the proportion of patients prescribed each class of GDMT was: 69% for Beta-blockers, 23% for Mineralocorticoid Receptor Inhibitors (MRA), 16% for Valsartan-Sacubitril and 7% for SGLT2 inhibitors. At 3-month follow-up, rates of GDMT prescription were improved: 90% for beta-blockers (p<0.01), 71% for MRA (p<0.01), 95% for ARNI (p<0.01) and 79% for SGLT2i (p<0.01). From baseline to follow-up echocardiogram, mean Left Ventricular End Diastolic Diameter improved from 5.51 to 5.13 cm (p<0.01). Mean Left Ventricular End Systolic Diameter improved from 4.33 to 3.75 cm (p<0.01). Mean Left Ventricular Mass Index was improved from 112.5 to 102.5 g/m2 (p<0.01). Mean Left Ventricular Ejection Fraction improved 34.4% to 49.8% (p<0.01). No hospitalizations due to medication-related adverse events were reported and 18 patients were hospitalized for HF exacerbation during study follow-up. Mean serum creatinine increased from 97.4 to 104.5 µmol/L (p<0.01); mean serum potassium increased from 4.48 to 4.58 (p<0.01). Conclusions This study demonstrates that a virtual program for GDMT optimization can safely and rapidly promote uptake of therapy in HFrEF patients. Furthermore, medical optimization was associated with significant reductions in left ventricular size, mass and ejection fraction. This provides a structural explanation for reductions in morbidity and mortality seen in STRONG-HF. Future studies should examine the effect of similar interventions on patient outcomes in a randomized setting.

Predictors of long-term outcomes of patients with concomitant moderate aortic and mitral valves diseases: a single tertiary care center experience 2010-2018

Abstract Background To date, moderate concomitant valvular heart diseases have been scarcely studied. This study aimed to further define predictors of long-term outcomes in patients diagnosed with concomitant moderate aortic and mitral valve disease at a tertiary center. Methods In this cohort we included 3257 patients (aged 71.7 ± 12.9 years; 55.2% male; 83.1% white) diagnosed with concomitant moderate aortic and mitral valves diseases who presented to the Cleveland Clinic between 2010 and 2018. The patients’ demographic, clinical and echocardiographic variables were collected. The primary endpoint of the study was the long-term composite outcome defined as heart failure hospitalization or all-cause mortality. We then conducted a univariate and multivariate cox proportional hazard survival analysis for the primary endpoint. Results The patients were followed up for 21.8 months. Baseline demographic characteristics are presented in table 1. Multiple demographic, clinical, and echo variables were evaluated. Using a univariate Cox proportional hazard survival analysis, older Age, history of smoking, Diabetes, Hypertension, Chronic Kidney Disease (CKD), Coronary Artery Disease (CAD), Atrial Fibrillation (Afib), Dyslipidemia, higher Right Ventricular Systolic Pressure (RVSP), higher New York Heart Association (NYHA) class, and lower Left Ventricular Ejection Fraction (LVEF) were associated with worse long-term outcomes. Additionally, patients who underwent an aortic (39.1%) or a mitral valve intervention (29.4%) were associated with better long-term outcomes (HR, 0.710, 0.708; respectively). In comparison, on Multivariable Cox analysis, female sex was significantly associated with worse survival (HR of 1.151, p-value=0.019). However, older Age, history of smoking, Diabetes, CKD, higher RVSP, NYHA class 2, 3, and 4, and lower LVEF remained significantly associated with worse long-term (table 2). Aortic valve intervention remained significantly associated with better survival (HR, 0.861, P-value=0.021). Compared to the Aortic Stenosis/ Mitral Stenosis (AS/MS) group, univariate analysis showed that patients in the Aortic Regurgitation/Mitral Regurgitation (AR/MR), and the AR/MS groups were significantly associated with better long term outcomes (HR, 0.738, HR, 0.575; respectively). Conversely, on Multivariate Cox analysis, AR/MR and AS/MR groups were significantly associated with better survival compared to AS/MS group (HR, 0.580, HR, 0.716; respectively). Conclusion In patients diagnosed with concomitant moderate aortic and mitral valve diseases, female sex, older age, history of smoking, diabetes, CKD, RVSP, NYHA class, LVEF and aortic valve intervention are independent predictors of the composite endpoint of heart failure hospitalization or all-cause mortality.Table 1Table 2

Impact of right ventricular-to-pulmonary artery coupling on remodeling and outcome in patients undergoing transcatheter edge-to-edge mitral valve repair.

Right ventricular-to-pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce. Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization and death. Between April 2018 and January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio < 0.36. Event-free survival rates at 2years were significantly lower among patients with impaired coupling (57 vs. 82%, p < 0.001), both in patients with primary (64 vs. 91%, p = 0.009) and secondary MR (54 vs. 76%, p = 0.026). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio < 0.36 was independently associated with outcome (adj.HR 2.74, 95% CI 1.17-6.43, p = 0.021). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ + 3mm, PASP: ∆ - 10mmHg, p for both < 0.001), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥ II: 77-54%, p < 0.001). TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome.

Right Atrial Phasic Function in Heart Failure with Preserved Ejection Fraction: Cardiac Magnetic Resonance Feature Tracking and Outcomes.

This study sought to investigate the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) and atrial fibrillation (AF). Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR, feature tracking of the RA wall was performed during CMR. In addition, all patients underwent right and left heart catheterization and 6 min walk distance (6MWD) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluations. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70 ± 8 years old) were included. Ninety-two patients (49%) were in persistent AF. Eighty-five patients reached the combined endpoint during a follow-up of 69 (42-97) months. After a multivariate cox regression analysis, the impaired RA reservoir strain (HR 0.949; 95% CI [0.909-0.990], p = 0.016), the RA reservoir strain rate (HR 0.991; 95% CI [0.983-0.999], p = 0.028), the RA conduit strain (HR 0.932; 95% CI [0.879-0.988], p = 0.019), and the RA conduit strain rate (HR 0.989; 95% CI [0.881-0.997], p = 0.011) were significantly associated with a worse outcome for patients in SR. In persistent AF, no RA imaging parameter was related to outcome after a multivariate regression analysis. In HFpEF patients in SR, CMR parameters of impaired RA conduit and reservoir function are associated with dismal cardiovascular outcomes. In persistent AF, RA parameters lose their prognostic ability.

Biventricular cardiac power reserve in heart failure with preserved ejection fraction.

Cardiac and extracardiac abnormalities play important roles in heart failure with preserved ejection fraction (HFpEF). Biventricular cardiac power output (BCPO) quantifies the total rate of hydraulic work performed by both ventricles, suggesting that it may help to identify patients with HFpEF and more severe cardiac impairments to better individualize treatment. Patients with HFpEF (n = 398) underwent comprehensive echocardiography and invasive cardiopulmonary exercise testing. Patients were categorized as low BCPO reserve (n = 199, < median of 1.57 W) or preserved BCPO reserve (n = 199). As compared to those with preserved BCPO reserve, those with low reserve were older and leaner, with more atrial fibrillation, higher N-terminal pro-B-type natriuretic peptide levels, worse renal function, more impaired left ventricular (LV) global longitudinal strain, worse LV diastolic function and right ventricular longitudinal function. Cardiac filling pressures and pulmonary artery pressures at rest were higher in low BCPO reserve, but central pressures were similar during exercise to those with preserved BCPO reserve. Exertional systemic and pulmonary vascular resistances were higher and exercise capacity was more impaired in those with low BCPO reserve. Reduced BCPO reserve was associated with increased risk for the composite endpoint of heart failure hospitalization or death over 2.9 (interquartile range 0.9-4.5) years of follow-up (hazard ratio 2.77, 95% confidence interval 1.73-4.42, p < 0.0001). Inability to enhance BCPO during exercise is associated with more advanced HFpEF, increased systemic and pulmonary vascular resistance, reduced exercise capacity and increased adverse events in patients with HFpEF. Novel therapies that enhance biventricular reserve merit further investigation for patients with this phenotype.

227 THE PROGNOSTIC VALUE OF RIGHT ATRIAL STRAIN IN PATIENTS WITH SECONDARY TRICUSPID REGURGITATION

Abstract Background in secondary tricuspid regurgitation (STR), the remodeling of the right ventricle (RV) and the right atrium (RA) is associated with different outcomes. However, the potential prognostic role of right RA function in this setting, assessed by 2D-speckle tracking echocardiography (2D-STE), remains to be tested. Accordingly, the aim of our study is to assess the prognostic value of RA 2D-STE in patients with significant (i.e. moderate or severe) STR. Methods we retrospectively studied 227 (mean age 74±14, 40% men, 59% sinus rhythm) consecutive patients with significant STR, acquired between May 2012 and June 2021. RA 2D-STE was obtained from a dedicated, non-foreshortened RV-focused apical 4-ch view, using a dedicated software package (AFI LA, EchoPAC 204, GE Vingmed, Horten, Norway). Among the three longitudinal strain components provided by the software package (reservoir, conduit and, contraction), we focused on RA longitudinal strain during reservoir (RASR). Patients were divided into two groups according to the median value of RARS (12%). A combined endpoint of heart failure hospitalization and all-cause mortality was defined. Results after a median follow-up period of 14 months (IQR, 1-27), 93 patients (41%) reached the combined endpoint. The predictive power of RARS&amp;lt;12% (AUC 0.64 [IC 95% 0.56-0.71]), was significantly higher than RA maximum volume (AUC 0.38 [IC 95% 0.31-0.47]). Patients with RARS ≤ 12% were more symptomatic (according to NYHA class), had larger RA volumes (119 vs 89 mL, p&amp;lt;0.001) and, a reduced right ventricular systolic function (TAPSE: 14.7 vs 18.9 mm; FAC 37.7 vs 42.4%; RV free-wall strain: 17.5 vs 20.8%; all p&amp;lt;0.001). In addition, patients with RARS&amp;lt;12% had more severe TR (corrected EROA: 0.85 vs 0.41 cm2; p&amp;lt;0.05). Prevalence of atrial fibrillation (58 vs 61%), left ventricular ejection fraction, and right ventricular size were similar between the groups. Patients with RARS ≤12% had a significant risk for death (log rank, p&amp;lt;0.001), even after correcting for confounding variables. Moreover, RA strain was independently associated with the combined endopoint in multivariate analysis (p &amp;lt; 0.001) Conclusions in patients with significant STR, RARS is an independent predictor of the combined endpoint of heart failure hospitalization and all-cause mortality and provides incremental prognostic value over RA volume.

Abstract 13749: Association of Left Atrial Hemodynamics by Cardiac Magnetic Resonance With Clinical Outcomes in Patients With Non-Ischemic Cardiomyopathy

Introduction: Left atrial hemodynamics are associated with clinical outcomes in a variety of cardiac conditions. We sought to assess the association of LA function and strain by cardiac magnetic resonance (CMR) in patients with non-ischemic cardiomyopathy (NICM) with clinical outcomes. Methods: We retrospectively evaluated 92 patients who were diagnosed with NICM and 50 controls without significant cardiovascular disease who underwent clinically indicated CMR and echocardiography. CMR was used to calculate indexed LA volumes (LAVi), ejection fraction (EF) and expansion index as well as measure LA reservoir (εR), conduit (εCD), and contractile strain (εCT). A multivariate regression analysis was performed with an endpoint of heart failure hospitalization (HFH). Results: Mean age for NICM patients was 59.6 ± 15.9 (64% males, 73% whites) versus 52.2 ± 12.4 (34% male, 64% white) for controls. Median follow-up was 58.9 months (IQR 57.1). LA EF and all LA strain components were significantly lower in NICM compared to controls (Table 1). On univariate analysis, mitral regurgitation, left and right ventricular EF, late gadolinium enhancement, εR, εCD, minimum and maximum LAVi were significantly associated with HFH. On multivariate analysis, after adjusting for the factors above and entering the LA parameters one at a time, εR was the only factor significantly associated with HFH (OR 0.98, CI 0.96-1.0). Adjusted Cox proportional hazard model for εR dociles (Median εR ~ 18) had a significant χ2 statistic of 21.1, p=0.03 (Figure). Conclusion: LA strain was significantly reduced in patients with NICM. Among all LA strain components, only εR was independently associated with HFH.

Abstract 13464: Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long Term Outcomes in Patients With Cardiac Amyloidosis

Introduction: We investigated left atrial (LA) function and strain by MRI in patients with cardiac amyloidosis (CA) and their associations with clinical outcomes. Methods: We conducted a retrospective case control study of 51 CA patients (24 transthyretin [ATTR] and 27 systemic [AL]) and 51 age, gender, and race matched controls without cardiovascular disease who underwent MRI in sinus rhythm. We measured LA function and strain parameters including indexed volumes (LAVi), ejection fraction, expansion index, reservoir (εR), contractile (εCT), and conduit (εCD) strain. A multivariate regression model was adjusted for age, hypertension, NYHA class, modified staging system (using Troponin-I, BNP, and GFR) and left ventricular ejection fraction (LVEF). We used endpoints of all-cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death. Results: Mean age was 65.3 for AL vs 76.2 for ATTR. ATTR patients had higher LAV, indexed LV and RV end systolic volumes and lower LVEF than AL patients. CA patients had significantly lower LA strain (11.5, 4.7, 6.8 vs 38.2, 14.2, 24 for εR, εCT, εCD respectively) and higher LAVs than controls. Median follow up was 12.6 months. εCT (OR 0.6, CI: 0.41-0.89), minimum LAVi (OR 1.06, CI: 1.02-1.13) and maximum LAVi (OR 1.08, CI: 1.01-1.15) were associated with the composite outcome of death or HFH. Cox Hazard regression models showed a difference in the composite outcome as LAVi increases and ↋CT is reduced. χ2 statistic were 23.1 for ↋CT versus 18.4 for LAVi (P=0.04, 0.01). Conclusion: In our retrospective study of CA patients, εCT, minimum and maximum LAVi were significantly associated with the composite outcome of death or HFH.

Abstract 14106: Prevalence and Respective Predictive Value of Late Gadolinium Enhancement Phenotypes in Patients Referred for Suspected Infiltrative Cardiomyopathy

Introduction: The respective value of different late gadolinium enhancement (LGE) phenotypes in patients with suspected infiltrative cardiomyopathy remains uncertain. Methods: In a large cohort of patients referred for suspected infiltrative cardiomyopathy, we evaluated respective associations between the dominant LGE phenotype and the composite endpoint of heart failure hospitalization, survived cardiac arrest or death. Kaplan-Meier survival curves were executed for six pre-defined LGE phenotypes. Multivariable analysis was performed to assess their independent association with the composite outcome, adjusted for relevant confounders. Final diagnosis was adjudicated using standardized disease-specific criteria. Results: 588 patients (68% male, median age 70 years, mean LVEF 54.7±12.7%) were studied. Of these patients, 139 (24%) were confirmed to have cardiac amyloidosis (CA) (81 [58%] transthyretin, 54 [39%] light chain and 4 [3%] undifferentiated) by objective non-CMR diagnostic criteria. Any LGE was present in 394 patients (67%) with the dominant phenotype being diffuse in 137 (23%), mid-wall patchy in 118 (20%), ischemic in 55 (9.4%), subepicardial in 18 (3.1%), mid-wall striae in 8 (1.4%), and RV insertion site in 58 (9.9%). The sensitivity and specificity of diffuse LGE for CA was 86% and 96%, respectively. Over a median 855 (IQR 372, 1542) days, 239 (41%) experienced the primary outcome. Unadjusted survival curves for each LGE phenotype are shown in the Figure. Following adjustment, diffuse (HR 2.30, p&lt;0.001), mid-wall patchy (HR 1.52, p=0.040) and ischemic LGE (HR 1.78, p=0.023) remained independently associated (Figure). Conclusions: In patients referred for suspected infiltrative cardiomyopathy, diffuse, mid-wall patchy and ischemic patterns all showed independent prognostic value. We confirm that diffuse LGE pattern reliably identifies CA patients with high sensitivity and specificity while delivering strong prognostic value.

Right atrial function in HFpEF in sinus rhythm vs. atrial fibrillation

Abstract Aims We sought to study the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF). Methods and results Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR during CMR feature tracking of the RA wall was performed (Figure 1). In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluation. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70±8 years old) were included of whom 96 (51%) were in SR. Eighty-five patients reached the combined endpoint during a follow-up of 72 (33–101) months. After multivariate cox regression analysis adjusted for age, NT-proBNP level, right ventricular ejection fraction and HF functional class, impaired RA strain (Figure 1A) (HR 0.959; 95% CI [0.924–0.996], P=0.024), RA conduit strain (Figure 1A) (HR 0.944; 95% CI [0.898–0.993], P=0.027) and RA conduit strain rate (Figure 1B) (HR 0.990; 95% CI [0.883–0.998], P=0.013) were significantly associated with adverse outcome for patients in SR (Table 1). In persistent AF, no RA imaging parameter was related to outcome after multivariate regression analysis. Conclusions In HFpEF patients in SR, CMR parameters of impaired RA conduit function show the best association with adverse cardiovascular outcome. In persistent AF, RA parameters lose their prognostic ability. Funding Acknowledgement Type of funding sources: None.

Right ventricular function and outcome in patients undergoing transcatheter mitral valve repair

Abstract Objectives This study sought to assess the impact of right ventricular dysfunction (RVD) on event-free survival after transcatheter mitral valve repair (TMVR) for severe mitral regurgitation. Background The prognostic value of left and RV global longitudinal strain (LV- and RV-GLS) on cardiovascular magnetic resonance feature tracking (CMR-FT) in patients undergoing TMVR is unknown. Methods Consecutive TMVR patients underwent pre-procedural and follow-up CMR-FT analysis. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization (HFH) and death. Results 62 patients (78.3±7.0y/o, 45% female, EuroSCORE-II: 9.6±7.1%) underwent CMR-FT prior to TMVR, 24% had concomitant tricuspid edge-to-edge repair (TTVR). On presentation, 23 (37%) patients suffered RVD, defined as RV-GLS &amp;gt;−20% on CMR-FT. RVD was associated with reduced LV and RV ejection fraction (LVEF: 39.2 vs. 48.7%, p=0.008, RVEF: 35.1 vs. 46.7%, p&amp;lt;0.001), as well as impaired LV-GLS (−14.0 vs. −19.5%, p=0.012). Eighteen events (12 deaths, 6 HFH) occurred during follow-up (11.4±9.1 months). On multivariable Cox-regression adjusted for baseline, procedural, imaging, and biomarker data, RV but not LV-GLS was significantly associated with outcome (adj.HR 2.50, 95% CI: 1.29–4.86, p=0.007 and 1.46, 95% CI: 0.50–4.28, p=0.491, respectively). Among various definitions of RVD on echocardiography and CMR, only RV-GLS on CMR-FT was significantly associated with outcome (RV-GLS &amp;gt;−20%: adj.HR 7.53, 95% CI: 2.07–27.42, p=0.002), but not RVEF on CMR or echo-indices of RV function (Central Illustration). Follow-up CMR-FT was performed in 21 (34%) patients and RV-GLS significantly improved after TMVR (−20.6 to −25.2%, p=0.016), irrespective of additional TTVR. Conclusions RV-GLS, as determined on CMR-FT, rather than LV-GLS or RVEF, is an independent predictor of outcome in patients undergoing TMVR. Funding Acknowledgement Type of funding sources: None.

Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long-Term Outcomes in Patients With Cardiac Amyloidosis.

Left atrial (LA) function and strain patterns by magnetic resonance imaging (MRI) have been investigated as markers of several cardiovascular pathologies, including cardiac amyloidosis (CA). However, associations with clinical outcomes have not been investigated. To compare LA function and strain by MRI in CA patients to a matched cohort of patients without cardiovascular disease (CVD) and evaluate the association with long-term clinical outcomes in CA patients. Retrospective case control. A total of 51 patients with CA and 51 age-, gender-, and race-matched controls without CVD who underwent MRI in sinus rhythm. ECG-gated balanced steady-state free precession sequence at 1.5T. All measurements were completed by one investigator (M.M.B.). LA function and strain parameters were measured including LA indexed minimum and maximum volumes, LA reservoir (R), contractile (CT), and conduit (CD) strain. We compared groups after adjusting for age, hypertension, New York Heart Association class, modified staging system (troponin-I, BNP, estimated GFR) and left ventricular ejection fraction (LVEF) for an endpoint of all-cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death. Differences between groups were evaluated with t tests for continuous variables or χ2 tests for categorical variables. A multivariable regression model was used to assess the associations of the P values-two-sided tests-<0.05 were considered statistically significant. CA patients with median follow up of 4.9 (8.5) months had significantly lower LA strain and higher LA volumes in comparison to the matched cohort. In the multivariable analysis, only LVEF was significantly associated with death while ƐCT (OR 0.6, CI: 0.41-0.89), indexed minimum LA volume (OR 1.06, CI: 1.02-1.13) and indexed maximum LA volume (OR 1.08, CI: 1.01-1.15) were significantly associated with the composite outcome of death or HFH. In this retrospective study of CA patients, ƐCT and indexed minimum and maximum LA volumes were significantly associated with the composite outcome of death or HFH. 3 TECHNICAL EFFICACY: Stage 3.

Left atrial reservoir strain as a predictor of cardiac outcome in patients with heart failure: the HaFaC cohort study

BackgroundThe left atrium (LA) is a key player in the pathophysiology of systolic and diastolic heart failure (HF). Speckle tracking derived LA reservoir strain (LASr) can be used as a prognostic surrogate for elevated left ventricular filling pressure similar to NT-proBNP. The aim of the study is to investigate the correlation between LASr and NT-proBNP and its prognostic value with regards to the composite endpoint of HF hospitalization and all-cause mortality within 1 year.MethodsOutpatients, sent to the echocardiography core lab because of HF, were enrolled into this study. Patients underwent a transthoracic echocardiographic examination, commercially available software was used to measure LASr. Blood samples were collected directly after the echocardiographic examination to determine NT-proBNP.ResultsWe included 174 HF patients, 43% with reduced, 36% with mildly reduced, and 21% with preserved ejection fraction. The study population showed a strong inverse correlation between LASr and log-transformed NT-proBNP (r = − 0.75, p < 0.01). Compared to NT-proBNP, LASr predicts the endpoint with a comparable specificity (83% vs. 84%), however with a lower sensitivity (70% vs. 61%).ConclusionLASr is inversely correlated with NT-proBNP and a good echocardiographic predictor for the composite endpoint of hospitalization and all-cause mortality in patients with HF.Trial registration:https://www.trialregister.nl/trial/7268

Baseline QRS Area and Reduction in QRS Area Are Associated with Lower Mortality and Risk of Heart Failure Hospitalization after Cardiac Resynchronization Therapy

Introduction: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure in selected patients. However, current guideline indications do not accurately predict individual prognosis with CRT, and up to 30% are nonresponders. Previous studies have shown that QRS area reduction following CRT is associated with improved survival. This study evaluates the incremental value of using QRS area derived from digital electrocardiogram (ECG) recordings, preoperatively and during CRT pacing. Methods: Medical records of 445 patients receiving CRT implants at a large-volume tertiary care center in Sweden were retrospectively evaluated. Digital ECG before and after CRT implantation were collected, and ECG parameters were analyzed in relation to a primary composite endpoint of heart failure hospitalization or death from any cause. Results: 147 patients (33%) reached the primary endpoint (93 deaths and 103 heart failure hospitalizations) over a median follow-up time of 2.7 years. A larger preimplant QRS area (HR, 0.89; [0.85–0.93]; p = <0.0001; adjusted HR, 0.93; [0.88–0.98]; p = 0.011) and a larger QRS area reduction (HR, 0.92; [0.88–0.96]; p = <0.0001; adjusted HR, 0.95; [0.90–0.99]; p = 0.042) postimplant correlated with a reduced risk of reaching the primary endpoint. This association was seen in patients with native left bundle branch block morphology, nonspecific intraventricular conduction delay, or paced ECG morphology but not in patients with right bundle branch block. Conclusion: Larger preimplant QRS area and QRS area reduction were associated with better clinical outcome following CRT in this retrospective material. This knowledge could help optimize patient selection and postoperative management.

812 Prognostic impact of the COAPT inclusion and exclusion criteria in real-world patients with secondary mitral regurgitation undergoing MitraClip implantation

Abstract Aims The COAPT randomized trial has shown a huge benefit in the survival of patients with s heart failure and functional mitral regurgitation treated with MitraClip. However, patients in COAPT were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear. Methods The present study examined the clinical outcome in consecutive patients with symptomatic moderate-to-severe or severe MR of dominant functional aetiology undergoing MitraClip therapy by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction &amp;gt;20%, left ventricular end-systolic dimension &amp;lt;70 mm, non-commissural primary jet, estimated pulmonary artery systolic pressure &amp;lt;70 mmHg, mitral valve orifice area &amp;gt;4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure). Results The composite endpoint of all-cause mortality or heart failure hospitalization and the endpoint of heart failure hospitalization were analysed. Among 118 patients who underwent MitraClip implantation 61% fulfilled the inclusion criteria of COAPT. The composite endpoint was significantly less frequent (P = 0.05) in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria, with an estimated 1-year event rate of 25% vs. 49%. Heart failure hospitalization was significantly less frequent (P = 0.04) in patients fulfilling COAPT selection criteria than in those who did not, with an estimated 1-year event rate of 19% vs. 36.8%. Conclusions In this single centre study the outcome of patients with functional mitral regurgitation undergoing MitraClip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility.

Prognostic impact of left atrial function in heart failure with preserved ejection fraction in sinus rhythm vs. persistent atrial fibrillation.

AimsWe sought to determine the prognostic impact of left atrial (LA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF).Methods and resultsWe enrolled consecutive HFpEF patients and assessed indexed LA volumes and emptying fractions (LA‐EF) on cardiac magnetic resonance imaging. In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N‐terminal prohormone of brain natriuretic peptide evaluation. We prospectively followed patients and used Cox regression models to determine the association of LA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70 ± 8 years old) were included of whom 92 (49%) were in persistent AF. Sixty‐five patients reached the combined endpoint during a follow‐up of 31 (9–57) months. Multivariate Cox regression adjusted for established risk factors revealed that LA‐EF was significantly associated with outcome in patients in SR [adjusted hazard ratio 2.14; 95% confidence interval (1.32–3.47) per 1‐SD decline, P = 0.002]. In persistent AF, no LA imaging parameter was related to outcome. By receiver operating characteristic and restricted cubic spline analyses, we identified an LA‐EF ≥ 40% as best indicator for favourable outcomes in patients with HFpEF and SR. Persistent AF carried a similar risk for adverse outcome compared with impaired LA‐EF (<40%) in SR (log‐rank, P = 0.340).ConclusionsIn HFpEF patients in SR, impaired LA‐EF is independently associated with worse cardiovascular outcome, which is similar to persistent AF. In persistent AF, LA parameters lose their prognostic ability.