Baseline Left Ventricular Ejection Fraction Research Articles

Abstract 10177: Pacing-Induced Cardiomyopathy: A Systematic Review and Meta-Analysis of Definition, Incidence, Risk Factors and Management

Introduction: Pacing-induced cardiomyopathy (PiCM) is a potential adverse sequela of right ventricular pacing. Definition varies between studies and the optimal management approach is uncertain. We aimed to characterize definition, incidence, risk factors and treatment strategies of PiCM. Methods: We performed a systematic review and meta-analysis of human studies that evaluated PiCM following pacemaker implantation identified through a literature search of PubMed and EMBASE up to March 2022. Included studies had fifty or more participants. We collected data regarding study definition of PiCM and calculated pooled prevalence across studies. Meta-analysis with random-effects modelling was used to assess association between risk factors and PiCM, reported as odds ratio (OR) with 95% confidence interval (CI). Results: Twenty-six studies (six prospective studies) with a total of 57993 patients (mean/median age 51-78 years, female 45%) were included in final analysis. Fifteen unique definitions of PiCM were reported; the most common definition was left ventricular ejection fraction (LVEF) <50% and LVEF decline ≥10% after pacemaker insertion. Pooled prevalence of PiCM was 12% (95%CI, 11-14%; Figure 1). On meta-analyses, risk factors included male sex (OR 1.23 95%CI 1.12-1.35), baseline LVEF (OR 0.95 per 1% increase, 95%CI 0.93-0.97), paced QRS complex duration (OR 1.02 per msec, 95%CI 1.01-1.03) and right ventricular pacing (RVP) burden (OR 1.02 per 1% increase, 95%CI 1.01-1.02). Treatment strategies identified included cardiac resynchronisation therapy (five studies) and his bundle pacing (three studies). Conclusions: Definition of PiCM varied significantly between studies. More than one in ten patients with a pacemaker with RV pacing developed PiCM. Risk factors included male sex, baseline LVEF, paced QRS duration and RVP. The optimal management strategy is not yet established. Further research is needed to define and treat this understated complication.

Abstract 12104: Pediatric Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)

Introduction: Left ventricular systolic dysfunction (LVSD, LV ejection fraction (LVEF) <50), occurs in ~8% of adults with hypertrophic cardiomyopathy (HCM) and is associated with poor prognosis. However, the incidence and prognosis of LVSD in pediatric patients with HCM (<18 years old) is poorly understood. Methods: Patients in SHaRe with pediatric HCM were included. Time-to-event analyses were performed to estimate 1) cumulative incidence of LVSD in pediatric vs adult HCM (Kaplan Meier), 2) predictors of incident LVSD in pediatric HCM (Cox-proportional hazards) and 3) a composite outcome of all-cause mortality, heart transplant and left ventricular assist device implant in pediatric HCM. Results: In total, 1296 pediatric HCM patients (34% females, median 12.2 years at diagnosis, median 8.3 years follow-up) were included. LVSD occurred in 155 (12%) of patients with 29% (n=45) having LVSD at the first SHaRe visit and 22% (n=34) developing LVSD <18 years old. At 5-year follow-up, the cumulative incidence of LVSD was 9% [8-11%]. Predictors of incident pediatric LVSD included HCM before age 12 (HR 2.0 [1.3-3.0]), female sex (HR 0.49 [0.32-0.77]), P/LP variants in thick filament genes (HR 2.6 [1.1-4.2], multiple P/LP variants (HR 9.1 [CI 2.9-29.1]) and baseline LVEF (HR 0.63 [0.58-0.68], per 5 %-points increase). Pediatric HCM was associated with higher rate of LVSD compared to adult-onset HCM (n=6428, median HCM at age 49 years, median follow-up of 7.1 years), p=0.05 (Figure 1). The composite endpoint occurred in 41% (n= 63/155) of children with HCM and subsequent LVSD. In patients with LVSD, female sex (HR 2.44 [1.41-4.17]) and baseline LVEF <35% (HR 4.0 [2.4-6.9]) were independently associated with the composite outcome. Conclusion: Females were less likely to develop LVSD but more likely to have adverse outcomes once they do. Clinical outcomes are adverse, and greater recognition of and surveillance for LVSD in pediatric HCM are warranted.

Abstract 11422: Factors Associated With Improvement of Left Ventricular Function After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure: A Multicenter Cohort

Introduction: Catheter ablation is a well-established therapy for atrial fibrillation (AF), with a promising impact on heart failure (HF) outcomes. We aimed to assess the impact of AF ablation on echocardiographic and clinical parameters in patients with HF, and to assess factors associated with improvement of the left ventricular ejection fraction (LVEF). Methods: Patients with HF and LVEF<50% who underwent radiofrequency AF ablation in 5 high-volume Brazilian centers were prospectively enrolled. All patients underwent transthoracic echocardiography before the procedure and during follow-up, and the analysis by the examiner was considered. The primary outcome was LVEF normalization (≥50%) at follow-up. Clinical, echocardiographic, and procedural variables associated with the primary outcome were assessed by logistic regression. Results: From 2018 - 2022, 85 patients were included, being 59 (69%) males, mean age 66±12 years. Of these, 27 were in NYHA functional class 3/4 and 71 (83%) had persistent AF. Pre-procedural LVEF was 38±7%, and 25 (29%) had LVEF<35%. Complications occurred in 3 patients (2 vascular access and 1 endocarditis). In the 12±10 month follow-up, there was a substantial improvement of the LVEF to 54±14% (p<0.001), and 60 (71%) achieved LVEF normalization. 59 patients (69%) had LVEF improvement ≥10%, only 6 remained in NYHA class 3/4, and AF recurred in 13 (15%). Three patients died during follow-up, and none had LVEF normalization. Predictors of LVEF normalization were: pre-ablation LVEF (OR=1.24, 95%CI 1.12-1.37), left atrial diameter (OR=0.88, 95%CI 0.82-0.95), Chagasic etiology (OR=0.14, 95%CI 0.03-0.77) and indication of amiodarone (OR=0.26, 95%CI 0.09-0.72) and ACEi/ARB (OR=0.25, 95%CI 0.08-0.75, p=0.02). In the multivariable model, independent predictors were: baseline LVEF (OR=1.25, 95% CI 1.10-1.41, p<0.001), left atrial diameter (OR=0.88, 95%CI 0.79-0.98, p=0.02), Chagasic etiology (OR=0.07, 95%CI 0.01-0.74, p=0.03) and indication of ACEi/ARB: (OR: 0.11, 95%CI 0.02-0.63, p=0.01). Conclusion: AF ablation in patients with HF resulted in echocardiographic and functional improvement, with low complication rates. Less clinical severity and morpho-functional impairment associated with LVEF normalization.

Abstract 13993: Sex Differences in Cardiac Structure and Function Following Acute Myocardial Infarction: Insights From the PARADISE-MI Echocardiographic Sub-Study

Introduction: Women have a higher incidence of heart failure (HF) hospitalizations than men following acute myocardial infarction (AMI). The extent to which differential cardiac remodeling between men and women might account for this higher risk in women is poorly understood. Hypothesis: Women and men have differences in cardiac remodeling after AMI that are predictive of clinical outcomes. Methods: The Prospective ARNI versus ACE inhibitor trial to Determine Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial randomized patients within 0.5 to 7 days of AMI complicated by left ventricular (LV) dysfunction, pulmonary congestion, or both to sacubitril/valsartan or ramipril. In the pre-specified echocardiographic sub-study, 544 participants were enrolled to undergo protocol echocardiography at the time of randomization and after 8 months. Results: At baseline, women (n=142, 26%) were older, more likely to have a history of hypertension, and less likely to have a history of MI. Women had a higher LV ejection fraction (LVEF), lower LV end-diastolic index (LVEDVi) and end-systolic volume index (LVESVi), and LV mass index, but no difference in left atrium (LA) volume index compared with men (Table). Women had better diastolic function compared with men. The absolute and relative changes in these echocardiographic parameters from baseline to 8 months were not significantly different between women and men. In univariate analyses, baseline LVEF, LVEDVi, LVESVi, LA dimensions and diastolic measurements are associated with primary outcome (Table). Conclusion: In PARADISE-MI, women have higher LVEF and lower indexed LV and LA chamber sizes compared to men following high-risk MI. The changes between baseline and 8-month in LVEF, LV and LA dimensions did not differ significantly between men and women, suggesting that differential cardiac remodeling post-MI may not account for the increased HF risk in women compared with men.

Abstract 15102: Short- versus Long-Term Recurrence of Ventricular Tachycardia in Non-Ischemic Cardiomyopathy: Is It Due to Incomplete Ablation During the Index Procedure or Progression of the Disease? Results From a Single-Center Study

Background: Non-ischemic cardiomyopathies (NICM) occur in the absence of contributory coronary artery disease or significant valvular heart disease. This study examined if VT recurrence post-scar-homogenization in NICM patients was due to progression of the disease after successful ablation or incomplete ablation during the index procedure. Methods: Consecutive NICM patients receiving redo procedure after their 1st VT ablation were included. All patients underwent bipolar substrate mapping with standard scar settings of normal tissue >1.5 mV and severe scar <0.5 mV. Endocardial scar homogenization was followed by heparin reversal with protamine and subsequent epicardial ablation. Disease progression was defined as extension of index scar area or appearance of new scar and decline in the baseline left ventricular ejection fraction (LVEF). Incomplete ablation was described as ablation within the index scar area that was ablated in the earlier procedure. Recurrence within 12 months was considered as early recurrence . Results: A total of 310 NICM patients (age: 60±13.5 years; male: 231 (74%); LVEF: 37±11%) undergoing their first VT ablation procedure were followed up for 7 years, of which 38 (12.2%) experienced recurrence and underwent re-ablation. Of the 38, 13 received repeat ablation at 5.07±2.56 months ( early recurrence ) and the remaining 25 patients had the redo at 40±21.78 months ( late recurrence ). In these 38 patients, mean LVEF was significantly lower at redo (pre-index: 35.3±10.6; pre-redo: 30.2± 7.07%, p=0.015). In the early-recurrence group , 10 (77%) had ablation sites located within the index scar (incomplete ablation) and 3 (33%) had extension of the index scar area (disease progression) detected. Index scars were mostly mid-myocardial (11, 84.6%). In the late-recurrence cohort , extension of the index scar area was detected in 12 (48%) and new scar were mapped in 19 (76%); none of these patients had incomplete ablation noted. Conclusion: In NICM patients, VT recurrence within 1-year of index procedure was mostly associated with incomplete ablation of mid-myocardial scars, whereas disease progression evidenced by detection of new scar, extension of preexisting scar and decline in LVEF was prevalent in patients with very late recurrence.

Abstract 14608: QRS Voltage in Lead V1 After Cardiac Resynchronization Predicts Survival in Patients With Left Bundle Branch Block

Introduction: The QRS complex on the electrocardiogram is a reflection of the summation of instantaneous electrical forces within the heart. In left bundle branch block (LBBB), the propagation of the electrical wavefront is dyssynchronous and unopposed and is thereby associated with an increase in the QRS voltage in precordial leads like lead V1, which are closer to perpendicular to the direction of propagation. Hypothesis: The aim of this study was to assess the impact of cardiac resynchronization therapy (CRT) on QRS morphology and voltage in lead V1, and its ability to predict response. Methods: The study included 103 consecutive patients with LBBB (age 69±12 years, 80 men, left ventricular ejection fraction 22±6%, QRS width 159±22ms), who received CRT for a median duration of 42 months (IQR 28-53 months). Results: During follow-up 18 patients died. Total QRS amplitude in lead V1 decreased significantly from 1.4±0.9mV at baseline to 0.8±0.5mV post CRT, (P value = 0.0002), the decrease being more pronounced in patients who survived when compared to nonsurvivors (0.8±0.9mV vs. 0.3±0.9mV P value= 0.021). The algebric sum of the positive and negative deflections of the QRS complex in V1 (sumQRS V1 ) changed significantly from -1.4±0.7mV at baseline to -0.05±0.7mV post CRT (p value <0.0001). Patients who survived had a more negative sumQRS V1 post CRT than nonsurvivors (-0.2±0.6mV vs +0.4±0.5mV p value=0.0012), and the sumQRS V1 cutoff that best separated survivors from non-survivors was +0.3mV. Patients with sumQRS V1 < 0.3mV had a significantly better survival than patients with sumQRS V1 ≥0.3mV (Figure). A >50% decrease in QRS amplitude in V1 with CRT, and sumQRS V1 post CRT <0.3mV independently predicted event free survival in a multivariate Cox regression model that included age, gender, baseline left ventricular ejection fraction and the change in QRS duration. Conclusions: Changes in QRS voltage in lead V1 after CRT predict survival in patients with LBBB.

Abstract 9395: Natural History of Myocardial Injury Following Covid-19 Vaccine Associated Myocarditis

Introduction: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. The natural history and clinical sequalae of this complication are of critical importance to estimate the impact on population health. Objective: To study the impact of COVID-19 vaccine associated myocarditis on convalescent myocardial health, symptoms, and clinical outcomes. Methods: This study was performed at two tertiary care hospitals. Baseline and convalescent (≥3 month) CMR imaging was performed for 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination and with no evidence of active viral infection. Global and segmental CMR-based markers of myocardial injury were studied at baseline and convalescence, inclusive of chamber volumetry, LV ejection fraction (LVEF), LV mass, T1 and T2 mapping, late gadolinium enhancement (LGE) imaging, and extracellular volume (ECV) fraction. Major clinical outcomes were captured. Results: The median age was 23.1 years (range 18-39 years) with 17 (85%) being male. Convalescent CMR evaluations were performed at a median (IQR) of 3.7 (3.3-6.2) months. Five patients (25%) had a baseline LVEF <50%. All patients showed abnormal LGE inclusive of a sub-epicardial pattern with a mean LGE burden of 8.6+/-5.3% LV mass using a >5SD of reference threshold. At follow-up, a mean 3% absolute improvement in LVEF was observed, accompanied by a 7% reduction in LVEDV and 5% reduction in LV mass (all p<0.015). Global LGE volume reduced by 66% (p<0.001). Absolute reductions in global T2, native T1, and ECV of 2.1msec, 58msec, and 2.9%, respectively were documented (all p≤0.001). All patients with LVEF <50% at baseline recovered above this threshold. However, 18 (90%) patients showed persistence of LGE at follow-up with 15% having a burden >5% of the LV mass. No patient experienced major clinical outcomes. Conclusion: COVID-19 mRNA vaccine associated myocarditis shows rapid improvement in CMR-based markers of tissue edema, contractile function, and LGE, and was not associated with adverse events at intermediate range follow-up. However, convalescent fibrosis was commonly observed, justifying ongoing need for clinical surveillance in this population.

Abstract 10944: Cardiac Magnetic Resonance Derived Left Atrioventricular Coupling Index and Major Adverse Cardiac Events in Patients Following Myocardial Infarction

Introduction: Recently a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scare we aimed to assess and validate the diagnostic and prognostic implications of LACI in a large AMI patient cohort. Methods: 1044 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed in median 3 days after AMI. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or congestive heart failure within 12 months after the index event were defined as primary clinical endpoint. Results: LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off of 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was independently associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4% - 14.9 %, p < 0.001) and maintained independence after adjusting for baseline confounders and left ventricular ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0 - 9., p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients according to traditionally utilized reduced LVEF ≤ 35 % (p < 0.001 on log-rank testing). Conclusions: Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond sole LA or LV volume analyses and EF especially in high-risk patients following AMI.

Abstract 14867: Examining Effects of a Physical Activity Intervention on Exercise Capacity and Cardiovascular Function Among Patients With Lymphoma and Breast Cancer Undergoing Treatment

Introduction. Patients receiving serial outpatient infusion treatment for lymphoma or breast cancer (BC) with potentially cardio-toxic chemotherapeutic regimens may experience declines in left ventricular ejection fraction (LVEF) and exercise capacity. This study sought to determine if a physical activity intervention (PAI) administered during cancer treatment could attenuate deterioration of exercise capacity and LVEF. Methods. Across two NCI funded cancer centers, we randomized (2:1) 34 participants to a home-based PAI or healthy living education intervention (HLI) within 6 weeks of initiating curative therapies for stage I-IV Hodgkin’s, non-Hodgkin’s lymphoma, or stage I-III BC (NCT01719562). Training programs were tailored by treatment and functional status and adapted for remote delivery during COVID-19. Exercise capacity was determined via cardiopulmonary exercise test (peak VO 2 [ml/kg/min]) and LVEF (%) was determined by magnetic resonance imaging at baseline, 3, and 6 months. Separate linear mixed-effects regression models controlling for baseline values examined changes in peak VO 2 and LVEF by time and treatment group. Results. Demographics were similar between the two arms (PAI vs. HLI, 52.4 [16.3] vs. 56.8 [12.7] years of age [SD]; 69% vs. 75% white; and 57.7% vs. 50% female). Peak VO 2 increased at 3 (+1.15 ml/kg/min [CI: -1.46 - 3.77]) and 6 months (+3.88 ml/kg/min [CI: 0.79 - 6.96]) in the PAI arm, while the HLI arm increased slightly at 3- (+0.67 ml/kg/min [CI: -5.14 - 6.48]) but not 6 months (-0.83 ml/kg/min [CI: -5.99 - 4.33]). LVEF declined slightly at 3 months in the PAI (-2.29% [CI: -4.83 - 0.25]) but not HLI arm (3.05.% [CI: -2.49 - 8.60]), while at 6 months, the PAI arm had returned to baseline LVEF (-0.58% [CI: -4.30 - 3.14]) and the HLI arm declined slightly (-1.76% [CI: -7.23 - 3.71]). Conclusions. This pilot RCT suggests the importance and utility of home-based physical activity during cancer treatment in protecting against expected declines in exercise capacity and LVEF. These results highlight the need for larger randomized trials that examine the effects of lifestyle interventions administered during treatment to improve quality of life and to support long term cardiovascular health in cancer survivors.

Abstract 10950: Prognostic Utility of Left Atrio-Ventricular Deformation Analysis in Heart Failure Patients Underwent Cardiac Resynchronization Therapy

Introduction: Left atrial (LA) adverse remodeling is a prognostic marker in patients with heart failure. Although left ventricular (LV) deformation analysis by speckle tracking method has been shown as a useful predictive marker after cardiac resynchronization therapy (CRT), the prognostic impact of baseline left atrio-ventricular functional deterioration on the outcome of patients underwent CRT implantation. Hypothesis: We hypothesized that a combination of LV and LA deformation assessments by speckle-tracking strain is of additive prognostic value in patients with CRT. Methods: We retrospectively analyzed 71 participants who received CRT implantation in the clinical guidelines. Global longitudinal strain (GLS) was defined as averaged strain from 3 apical views. LA strain (LAS) was calculated as the average strain using apical two- and four-chamber views. The endpoint was composite outcome of death, hospitalization due to worsening HF for 5 years after CRT implantation. Results: Out of 71 patients aged 68 ± 11 years with 162±24ms of QRS duration and 30±8% of LV ejection fraction, 40 patients (56%) met the endpoint. The patients were stratified using median value of LAS (-15%) and GLS (-8%). LAS and GCS remained significantly associated with poor outcome after adjusting for LVEF (LAS hazard ratio, 0.92; p<0.001; GLS hazard ratio, 1.15; p = 0.01). Kaplan-Meier analysis showed that the subgroup of patients with both lower median values of LAS and GLS had the worst outcomes over 5 years (Figure, Log-rank, p = 0.008). In the sequential Cox model, predictive value of baseline LV ejection fraction (χ2 = 4.9) was improved by the addition of GLS (χ2 = 9.2, p = 0.037), and further improved by the addition of LAS (χ2 = 15.8, p = 0.005). C-statistics also improved from 0.62 to 0.73. Conclusions: Baseline left atrio-ventricular functional deterioration by deformation analysis were significantly associated with poor outcome after CRT implantation.

Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial.

Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF). This is a prespecified analysis of the randomized, double-blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure (HF), clinical signs of volume overload (eg, edema, pleural effusion, or ascites), NTproBNP (N-terminal pro-B-type natriuretic peptide) >1000 ng/L, or BNP (B-type natriuretic peptide) >250 ng/mL to receive intravenous acetazolamide (500 mg once daily) or placebo in addition to standardized intravenous loop diuretics (twice that of the oral home maintenance dose). Randomization was stratified according to LVEF (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload within 3 days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output. Median LVEF was 45% (25th to 75th percentile; 30% to 55%), and 43% had an LVEF ≤40%. Patients with lower LVEF were younger and more likely to be male with a higher prevalence of ischemic heart disease, higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide to the primary end point of successful decongestion (OR, 1.77 [95% CI, 1.18-2.63]; P=0.005; all P values for interaction >0.401) was found when LVEF was assessed per randomization stratum (≤40% or >40%), or as HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction, or on a continuous scale. Acetazolamide resulted in improved diuretic response measured by higher cumulative diuresis and natriuresis and shortened length of stay without treatment effect modification by baseline LVEF (all P values for interaction >0.160). When added to treatment with loop diuretics in patients with acute decompensated HF, acetazolamide improves the incidence of successful decongestion and diuretic response, and shortens length of stay without treatment effect modification by baseline LVEF. URL: https://www. gov; Unique identifier: NCT03505788.

Right ventricular dysfunction in patients with new-onset heart failure: longitudinal follow-up during guideline-directed medical therapy.

Improvement in left ventricular ejection fraction (LVEF) after up-titration of guideline-directed medical therapy (GDMT) has been well described in heart failure (HF) patients. Less is known about the prevalence and clinical course of right ventricular dysfunction (RVD) in patients with new-onset HF. From 2012 to 2018, 625 patients with a recent (<3 months) diagnosis of HF were referred to a specialized nurse-led HF clinic for protocolized up-titration of GDMT. RVD, defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm, was assessed at baseline and at the follow-up visit. Patients were followed for the combined endpoint of all-cause mortality and HF hospitalization for a mean of 3.3 ± 1.9 years. Of the 625 patients, 241 (38.6%) patients had RVD at baseline. Patients with RVD were older, more symptomatic, had a lower LVEF, and more often had a history of cardiothoracic surgery and atrial fibrillation. After a median follow-up of 9 months, right ventricular function normalized in 49% of the patients with baseline RVD. RVD at baseline was associated with a higher risk of the combined endpoint (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.21-2.18). Right ventricular function normalization was associated with a lower risk for the combined endpoint (HR 0.56, 95% CI 0.31-0.99), independent of baseline TAPSE, age, sex, and LVEF. More than one-third of patients with new-onset HF have RVD. RVD is associated with a higher risk of all-cause mortality and HF hospitalization. Recovery of RVD regularly occurs during up-titration of GDMT and is associated with improved clinical outcomes.

Left Atrial Reverse Remodeling in Dilated Cardiomyopathy

Left atrial (LA) dilation is associated with a worse prognosis in several cardiovascular settings, but therapies can promote LA reverse remodeling. The aim of this study was to characterize and define the prognostic implications of LA volume index (LAVI) reduction in patients with dilated cardiomyopathy (DCM). Consecutive patients with DCM from two tertiary care centers, with available echocardiograms at baseline and at 1-year follow-up, were retrospectively analyzed. LA dilation was defined as LAVI > 34mL/m2, and change in LAVI (ΔLAVI) was defined as the 1-year relative LAVI reduction. The outcome was a composite of death, heart transplantation (HTx), or heart failure hospitalization (HFH). Five hundred sixty patients were included (mean age, 54±13years; mean left ventricular ejection fraction, 31±10%; mean LAVI, 45±18mL/m2). Baseline LAVI had a non-linear association with the risk for death, HTx, or HFH, independent of age, left ventricular ejection fraction, mitral regurgitation, and medical therapy (P<.01). At 1-year follow-up, LAVI decreased in 374 patients (67%; median ΔLAVI, -24%; interquartile range, -37% to -11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline left ventricular ejection fraction. After multivariable adjustment, ΔLAVI showed a linear association with the risk for death, HTx, or HFH (hazard ratio, 0.96 per 5% decrease; 95% CI, 0.93-0.99; P=.042). At 1-year follow-up, patients with reductions in LAVI of >10% and LAVI normalization (i.e., follow-up LAVI≤34mL/m2; 31% of the overall cohort) were at lower risk for death, HTx, or HFH (hazard ratio, 0.37; 95% CI, 0.35-0.97; P=.028). In a large cohort of patients with DCM, 1-year reduction in LAVI was observed in a number of patients. The association between reduction in LAVI and death, HTx, or HFH suggests that LA structural reverse remodeling might be considered an additional parameter useful in the individualized risk stratification of patients with DCM.

Comparison of Patients with Reduced and Mildly Reduced Left Ventricular Ejection Fraction: Intermediate Data from the FAR NHL Registry

Introduction: We present the results of a study by the Pharmacology and NeuroHumoral Activation Registry (FAR NHL), which collects data on patients with chronic heart failure. The register contains 1088 patients from three workplaces in the Czech Republic which specialize in the care of patients with heart failure. Objectives: The aim was to obtain a comparison of pharmacotherapy and the incidence of comorbidities in patients with reduced ejection fraction (HFrEF) versus patients with mid-range (or newly mildly reduced) ejection fraction (HFmrEF). Methods: Patients with a baseline left ventricular ejection fraction below 50% were included and divided into HFrEF with EF below 40% and HFmrEF with EF 40–49%, according to the 2016 ESC Guidelines. In addition to the clinical condition, we also monitored laboratory parameters, comorbidities and pharmacotherapy in the patients. Results: Patients with HFrEF versus HFmrEF are more likely to be male (p &lt; 0.008), younger (p &lt; 0.001), have lower systolic blood pressure and are less likely to have ischemic etiology of heart failure (p &lt; 0.001). There were no differences between the groups in the proportion of comorbidities: hypertension, diabetes mellitus, dyslipidemia, ischemic lower limb disease or chronic obstructive pulmonary disease. There were no differences in the proportion of smokers and non-smokers between the groups. Patients with HFrEF have a higher class of New York Heart Association (NYHA), a level of N-terminal fraction of natriuretic peptide B (NT-proBNP), and a higher level of urea and uric acid. They are more often treated with loop diuretics or mineral corticosteroid receptor (MRA) blockers and less often with thiazides (p &lt; 0.001), and also have a worse two-year prognosis. Conclusion: Compared to patients with HFmrEF, patients with HFrEF have more severe heart failure, more pronounced neurohumoral activation and a worse prognosis. They do not differ in the presence of comorbidities.

The impact of complete versus partial preservation of the sub-valvular apparatus on left ventricular function in mitral valve replacement.

In mitral valve replacement (MVR), sudden increases in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes left ventricular(LV) dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favorable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). We retrospectively analyzed a cohort of 29 MVR-P and 19 MVR-C patients with complete echocardiography data at our unit, who were operated between 2008 and 2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51%- 60%). Baseline GLS was -18.4 (-21.2 to -15.5). There were no significant between-group differences between all baseline demographics and echocardiographic markers. There was significantly higher absolute postoperative LVEF in MVR-C patients (p = 0.029). There was also significant worsening in LVEF (p = 0.0121) and GLS (p < 0.0001) after MVR-P and not MVR-C, suggesting no reduction in LV function post-MVR-C but a reduction post-MVR-P. There was significantly less postoperative worsening of GLS per patient in MVR-C group as compared to the MVR-P group (p = 0.023), indicating better preservation of LV function. There was also a smaller decline in LVEF per patient in the MVR-C as compared to the MVR-P group, although not statistically significant (p = 0.23). MVR with complete preservation of the sub-valvular apparatus shows a favorable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.

Feasibility of Left Bundle Branch Area Pacing Combined with Atrioventricular Node Ablation in Atrial Fibrillation Patients with Heart Failure.

Background: Pacemaker implantation combined with atrioventricular node ablation (AVNA) could be a practical choice for atrial fibrillation (AF) patients with heart failure (HF). Left bundle branch area pacing (LBBaP) has been widely reported. Objectives: To explore the safety and efficacy of LBBaP combined with AVNA in AF patients with HF. Methods and results: Fifty-six AF patients with HF attempted LBBaP and AVNA from January 2019 to December 2020. Standard LBBaP was achieved in forty-six patients, and another ten received left ventricular septal pacing (LVSP). The cardiac function indexes and pacemaker parameters were evaluated at baseline, and we conducted a 1-month and 1-year follow-up. Result: At the time of implantation and 1-month and 1-year follow-up, QRS duration of LVSP group was longer than that of LBBaP group. The pacemaker parameters remained stable in both the LBBaP and LVSP groups. At 1-month and 1-year follow-up after LBBaP and AVNA, left ventricular ejection fraction, left ventricular end-diastolic diameter, and NYHA classification continued to improve. Baseline left ventricular ejection fraction and QRS duration change at implantation can predict the magnitude of improvement of left ventricular ejection fraction at 1-year after LBBaP. Baseline right atrial left-right diameter, the degree of tricuspid regurgitation, and interventricular septum thickness may be the factors affecting the success of LBBaP. Conclusion: LBBaP combined with AVNA is safe and effective for patients with AF and HF. Baseline right atrial left-right diameter, the degree of tricuspid regurgitation, and interventricular septum thickness may be the factors affecting the success of LBBaP.

Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e'lat (P=0.005), decrease in E/e'lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort. URL: https://www. gov; Unique identifier: NCT02924727.

CRT-D non-responders have worse cardiovascular outcome than patients after primary ICD implantation with similar baseline left ventricular ejection fraction

Abstract Background Cardiac resynchronisation therapy (CRT) fails to improve echocardiographic parameters and outcome in 20–40% of heart failure (HF) patients with reduced ejection fraction (EF) referred to as CRT non-responders (CRT-NR). The aim of this study was to compare the outcomes of CRT-NR patients who received a CRT defibrillator (CRT-D) device with patients after primary implantable cardioverter-defibrillator (ICD) implantation for impaired left ventricular (LV) function. Methods CRT-NR status was defined as no or less than 10% improvement in LV EF 12 months post implantation. CRT-NR patients and those after primary ICD implantation for LV EF&amp;lt;35% were identified in our database between 2010 and 2019. CRT-NR patients were further categorized as progressors (decrease in LV EF ≥5%) or non-progressors (LV EF change between +9 to −5%). Primary endpoint was all-cause mortality or the need for heart transplantation during follow-up. Statistical significance was assessed by Log-rank test of Kaplan-Meier survival analysis. Results 151 CRT-NR patients and 219 patients after primary ICD implantation were identified with a mean ± SEM follow-up of 43.7±2.5 and 47.3±2.2 months, respectively. Baseline (preoperative) LV EFs were higher (p&amp;lt;0.05) for the overall CRT-NR group (EF = 27.4±0.4%) than for the ICD group (EF = 25.2±0.3%) Further, both CRT-NR subgroups of progressors (n=49; EF = 28.6±0.7%) and non-progressors (n=102; EF = 26.9±0.5%) had also significantly higher baseline LV EF as compared to ICD patients (p&amp;lt;0.05). No statistical significance was found between the two CRT-NR subgroups. Event free median survival for the overall CRT-NR group (55.6 months) was significantly worse than for the ICD group (79.6; p&amp;lt;0.05). This difference was driven by progressor patients who had a significantly worse event free survival (37.8 months, p&amp;lt;0.05) than ICD patients, while vent free survival in non-progressors (60.8 months) was comparable to ICD patients (p=0.18). Conclusion Progressor subgroup of CRT-NR have worse outcome as compared to non-progressors and also to those after primary prevention ICD implantation. The poor prognosis of these patients should have implications for timely decision regarding all therapeutic measures currently available for the management of heart failure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Developement and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme

Quality of life in patients with heart failure and improved ejection fraction: one year changes and prognostic implication

Abstract Background Inconsistent and controversial results have been reported about the association of quality of life (QoL) and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). The 2021 universal definition of HF specifically describes the criteria for the patients with HF and improved LVEF (HFimpEF): HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF &amp;gt;40%. Purpose 1) To assess whether patients with HF and reduced LVEF (HFrEF) at first visit in an outpatient HF Clinic that fulfil the HFimpEF criteria one year later presented a higher improvement in QoL assessed by the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) than those patients that did not fulfil HFimpEF criteria. 2) To assess the prognostic role of QoL on outcomes in HFimpEF patients. Methods In a prospective registry of real-life HF outpatients LVEF and QoL evaluated by MLWHFQ were assessed at first visit at the HF Clinic and at one year of follow-up. Results From August 2001 to August 2021, baseline and one year LVEF and MLWFQ scores were available in 1040 patients with an initial LVEF ≤40%. Table 1 shows baseline demographic and clinical characteristics of patients. In summary, mean age was 65.2±11.7 years, 75.9% of the patients were men, the main aetiology was ischaemic heart disease (52.9%) and patients were mostly in New York heart Association (NHYA) class II (71.1%) and III (21.6%). Baseline LVEF was 28.5% ± 7.3 and baseline MLWHFQ score was 30.2±19.5. At one year, mean LVEF increased to 38.0±12.2 while MLWHFQ scores improved to 17.4±16.0. There were 361 patients that fulfilled the HFimpEF criteria (34.7%). These patients significantly and markedly improved both LVEF (from 28.7±6.6 to 50.9±7.6, p&amp;lt;0.001) and QoL (from 32.9±20.6 to 16.9±16.0, p&amp;lt;0.001). Although in patients that did not fulfil the criteria of HFimpEF both LVEF (from 28.4±7.6 to 31.1±7.9, p&amp;lt;0.001) and QoL (from 28.7±18.8 to 17.6±15.9, p&amp;lt;0.001) also significantly improved, the improvement in QoL was significantly higher in HFimpEF patients (−16.0±23.8 vs. −11.1±20.3, p=0.001), taking into account that baseline MLWHFQ score was worse in HFimpEF patients (p=0.001). However, at one year QoL was similar when both groups were compared (p=0.50). MLWHFQ score at one year proved to be superior to QoL improvement (using a cut-off of at least 5 points) from the prognostic point of view. Conclusions QoL improved both in patients with and without HFimpEF criteria, and QoL perception at one year was similar in both groups, suggesting the influence of other factors other than LVEF in QoL perception. QoL at one year revealed to be superior to QoL changes from baseline from the prognostic point of view. Funding Acknowledgement Type of funding sources: None.

Heart failure with improved ejection fraction (HFimpEF) in patients treated with sacubitril/valsartan (SV)

Abstract Introduction Several studies demonstrated that patients with improvement of left ventricular ejection fraction (LVEF) and symptoms had good prognosis in heart failure with reduced ejection fraction (HFrEF). Based on these results, new classification of HF according to LVEF was currently proposed. Sacubitril/valsartan (SV) is recommended as one of the first-line therapy of HFrEF patients. SV reduced hospitalization for HF and cardiovascular mortality compared to enalapril in PARADIGM-HF trial. However, it is unclear that patients with improvement of LVEF also have better prognosis compared to patients without LVEF improvement among patients treated with SV. Purpose We aimed to evaluate the clinical characteristics and outcomes of heart failure with improved ejection fraction (HFimpEF) in heart failure with reduced ejection fraction (HFrEF) patients treated with SV. Methods We analyzed 230 patients with HFrEF taking SV in a multicenter retrospective cohort (RECORD-SV registry) from 2017 to 2019. Enrolled 230 patients were performed baseline and 1-year follow-up echocardiography. Based on 2 echocardiographic results, we defined “HFimpEF” as HF with a baseline LVEF ≤40%, ≥10% increase from baseline LVEF and a follow-up measurement of LVEF &amp;gt;40%. Others were defined as “Persistent HFrEF”. We analyzed and compared clinical characteristics and outcomes between two groups. Primary endpoint was a composite outcome of all-cause death and hospitalization for HF (HHF). Results From 230 patients, 65 patients with HFimpEF and 165 patients with Persistent HFrEF were analyzed. The median follow-up duration was 557 days (interquartile range 364 to 727 days). Patients with HFimpEF had a higher prevalence of female gender (50.8% vs. 30.3%) and de novo HF (44.6% vs. 21.2%). There were no significant differences for age, etiology (ischemic vs. non-ischemic), diabetes, atrial fibrillation, hypertension, and HF medications including SV dose between two groups. Patients with HFimpEF showed lower rate of all-cause death or HHF as a primary endpoint compared to patients with persistent HFrEF (6.2% vs. 22.4%; IPTW adjusted HR 0.24; 95% CI 0.13–0.46; p&amp;lt;0.001) (Table 1). It was also shown that HFimpEF patients had a reduced risk of primary endpoint in the Kaplan-Meier curves compared with persistent HFrEF (Log-rank p=0.045) (Figure 1). We demonstrated that Non-prior MI (adjusted OR 7.29; 95% CI 1.50–35.36; p=0.014) and de novo HF (adjusted OR 4.33; 95% CI 1.70–11.04; p=0.002) were independent prognostic factors of HFimpEF in HFrEF patients treated with SV. Conclusions HFimpEF patients had better clinical outcomes compared to those with persistent HFrEF in HFrEF patients treated with SV. Non-prior MI and de novo HF were independent predictors of HFimpEF in patients treated with SV. Funding Acknowledgement Type of funding sources: None.