Higher Left Ventricular Ejection Fraction Research Articles

Finerenone in Women and Men With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

Sex is associated with the clinical presentation, outcomes, and response to treatment in patients with heart failure (HF). However, little is known about the safety and efficacy of treatment with finerenone according to sex. To estimate the efficacy and safety of finerenone compared with placebo in both women and men. Prespecified analyses were conducted in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF). The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction (LVEF) of 40% or greater randomized between September 2020 and January 2023. Finerenone (titrated to 20 mg or 40 mg) or placebo. The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events (unplanned HF hospitalizations or urgent HF visits). A total of 6001 patients were randomized in FINEARTS-HF, of whom 2732 were women (45.5%), with a mean (SD) age of 73.6 (9.1) years. Women had higher rates of any obesity, higher LVEF (54.6 [7.6%] vs 50.9 [7.6] for men), lower mean (SD) estimated glomerular filtration rate than men (59.7 [19.1] vs 64.1 [20.0] for men; P<.001) , worse New York Heart Association functional class, and lower Kansas City Cardiomyopathy Questionnaire-Total Symptom Scores (KCCQ-TSS) (mean [SD] 62.3 [24.0] vs 71.0 [23.1]). The incident rate of the primary outcome was slightly lower in women (15.7; 95% CI, 14.3-17.3) than in men (16.8; 95% CI, 15.4-18.3) per 100 person-years. Compared with placebo, finerenone reduced the risk of the primary end point similarly in women and men: rate ratio 0.78 (95% CI, 0.65-0.95) in women and 0.88 (95% CI, 0.74-1.04) in men (P = .41 for interaction). Consistent effects were observed for the components of the primary outcome and all-cause mortality. The mean increase (improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone, regardless of sex (P = .73 for interaction). Finerenone had similar tolerability in women and men. In FINEARTS-HF, finerenone reduced the risk of the primary end point similarly in women and men with heart failure with mildly reduced or preserved ejection fraction. Finerenone had similar tolerability in women and men. ClinicalTrials.gov Identifier: NCT04435626.

Abstract 4127562: Age, Adiposity-Related Anthropometrics, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Trials

Background: Age has been shown to modify the population-level association between body mass index (BMI) and mortality. However, whether age modifies the association between adiposity-related anthropometrics and adverse outcomes in heart failure (HF) populations has not been systematically explored. Methods: In this participant-level pooled analysis of five international, multicenter, randomized-controlled trials enrolling adults with HF and either mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), the association between age and adiposity-related anthropometrics (BMI, waist circumference [WC], and waist-to-height ratio [WHtR]) and the primary composite outcome of time-to-first HF hospitalization or cardiovascular (CV) death was evaluated using multivariable adjusted Cox proportional hazards models (stratified by treatment and trial) and restricted cubic splines. Results: Among 21,606 participants in the analysis (mean age, 71±9 years; 49% female; 83% White; mean BMI, 30±6 kg/m 2 ), 5,350 (25%) were aged &lt;65 years, 8,273 (38%) were aged 65-74 years, and 7,983 (37%) were aged ≥75 years at baseline. Older individuals were more likely to be female, have lower BMI and WC, and higher left ventricular ejection fraction. Overall, BMI, WC, and WHtR were steeply and non-linearly associated with the primary outcome ( Figure ). Age, as either a categorical or continuous variable, significantly modified the covariate-adjusted association between all anthropometrics and the primary composite outcome ( P ≤0.001 for all) ( Figure ). A J-shaped relationship, characterized by higher incidence of the primary outcome with lower anthropometric values, was observed only for BMI and was substantially attenuated among younger adults. Irrespective of the anthropometric used, increasing adiposity was most steeply associated with primary events among adults aged &lt;65 years. Conclusions: In this pooled analysis of HFmrEF/HFpEF trials, age was a powerful modifier of the relationship between excess adiposity and HF hospitalization or CV death. An “obesity-survival paradox” – observed only for BMI – was not apparent in younger participants, who exhibited the steepest increase in the rate of clinical events with higher adiposity.

Abstract 4141480: Gender differences in bifurcation percutaneous coronary interventions: Update from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION)

Background: Gender differences on short and long-term outcomes following bifurcation percutaneous coronary intervention (PCI) have received limited study. Research Questions: To examine gender differences in outcomes of bifurcation PCI. Methods: We examined the angiographic, procedural characteristics, and outcomes of 1084 bifurcation PCIs (1076 patients) performed at five centers between 2013-2024 from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION). Results: Women represented 25.19% of the entire study population. They were older (68.37±12.34 vs 66.09±11.54; p=0.001), less likely to be currently smokers (13.7% vs 20.4%; p=0.014), with higher left ventricular ejection fraction (%) (55.46±13.27 vs 53.16±12.55; p&lt;0.001) and lower baseline creatinine (0.85 vs 1.00; p&lt;0.001). Lesion characteristics were mostly similar, with slightly lower proximal and distal main vessel diameter in women. Their proximal main vessel was more likely to be left anterior descending artery (46.5% vs 39.4%; p=0.030) and less likely to be right coronary artery (10.3% vs 16.1%; p=0.030), compared to men. Technical success was similar (94.5% vs 94.6%; p=0.952), while procedural success was lower (89.6% vs 94.1%; p=0.011). In-hospital major adverse cardiac events (MACE) were more common in women (8.5% vs 4.2%; p=0.007), which presented with increased in-hospital mortality (4.1% vs 0.6%; p&lt;0.001), stroke (1.8% vs 0.1%; p=0.005) and bleeding (1.8% vs 0.2%; p=0.013). Their PCIs required equal procedure time, but lower fluoroscopy time, contrast volume and air kerma radiation dose. Female gender was independently associated with higher in-hospital major adverse cardiac events (MACE) (odds ratio (OR) 2.21; 95%CI 1.23-3.95; p=0.008) and lower procedural success (OR 0.56; 95%CI 0.32-1.00; p=0.044). Follow-up data were available for 733 patients (68.12%). The incidence of follow-up MACE was significantly higher in women (hazard ratio (HR) 1.36; 95%CI 1.02-1.81; p=0.038), while on adjusted mixed Cox proportional hazards analysis female gender was associated with higher follow-up MACE (HR 1.58; 95%CI 1.08-2.30; p=0.018). The incidence of follow-up mortality was similar between genders (HR 1.17; 95%CI 0.78-1.77; p=0.45). Conclusions: Bifurcation PCI can be accomplished with high technical success in women, but higher in-hospital and follow-up MACE, compared to men.

Abstract 4122247: Impact of serum chloride levels for ventricular arrhythmias in patients with heart failure undergoing cardiac resynchronization therapy

Background: As previous reports of ventricular arrhythmia (VA) as a prognostic marker of mortality in heart failure (HF) patients included those with implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices, little is known about the risk factors of VA among patients undergoing cardiac resynchronization therapy (CRT), especially those without previous VA. The prognostic role of electrolyte abnormalities has been highlighted in HF patients. This study evaluated the impact of serum chloride levels for VA and all-cause death in patients with HF who underwent CRT without VA before CRT implantation. Methods: From the retrospective cohort of 397 HF patients (age 63+/-13, male 74%) who undergoing CRT implantation between 2010 and 2020, this study enrolled 175 patients (82% implanted CRT with a defibrillator) without a previous history of VA (sustained ventricular tachycardia (VT) of ventricular fibrillation (VF)). We studied the impact of serum chloride levels before CRT implantation. The primary endpoint was defined as VA, VA with ICD therapy and sudden cardiac death. The secondary endpoint was all-cause mortality. Results: During median follow-up of 35 months, 53 patients (30%) experienced VA. Patients with VA had a tendency toward high LVESV (172ml vs. 150ml, p&lt;0.09) and low left ventricular ejection fraction (26 vs. 29, p&lt;0.09), and significantly reduced rate of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (30% vs. 70%, p&lt;0.05) at the time of CRT implantation. The rate of CRT responders was significantly higher in patients without VA than with VA (59% vs. 40%, p&lt;0.05). The cut-off value of chloride for VA was determined to be 102mEq/l using receiver operating characteristic analysis. The patients with chloride ≤102mEq/l had significantly higher rates of VA (41% vs. 25%, log-rank p&lt;0.05) and mortality (33% vs. 18%, log-rank p&lt;0.05) (Figure). By multivariate cox analysis, the level of chloride had an independent predictive value of VA in patients with CRT (hazard ratio [HR] 1.08 per 1mEq/l decrease, 95% confidence interval [CI] 1.00-1.16, p&lt;0.05) (Table). Conclusions: The chloride level had a predictive value for VA after CRT implantation in HF patients without previous VA. The management of electrolytes, including chloride, might be important for preventing fatal arrhythmia in patients with HF undergoing CRT implantation.

High frequency of occult transthyretin and apolipoprotein AI–type amyloid in aortic valves removed by valve replacement for aortic stenosis

Background A high incidence of valvular involvement of amyloid in the setting of aortic stenosis (AS) has been reported. Amyloid derived from ApoAI (AApoAI) can form local amyloid deposits in the aortic valve. Although a high prevalence of concomitant severe AS and cardiac transthyretin-type amyloidosis (ATTR) has been reported, the prevalence of valvular involvement by ATTR and AApoAI is unclear. Methods Using immunostaining and mass spectrometry, we analysed amyloid proteins in 97 aortic valves removed for valve replacement due to AS at Kyoto Prefectural University of Medicine between 2014 and 2021. Clinical information was also reviewed. Results Amyloid deposits were found in 44 cases (45%), of which 30 cases (68%) involved ATTR and 33 cases (75%) AApoAI. Statistical analysis showed significantly lower age and E/e′ among amyloid-positive cases compared with amyloid-negative cases and significantly lower brain natriuretic peptide, higher fractional shortening, and higher left ventricular ejection fraction among ATTR-positive cases compared with ATTR-negative cases. Seven recent patients underwent bone scintigraphy and ATTR cardiomyopathy was observed in only one case. Conclusions AS symptoms can manifest earlier in patients with amyloid or ATTR deposition in the aortic valve than in patients without such deposition, even though left ventricular function is preserved.

Non-invasive assessment of left ventricular hemodynamic forces in hypertrophic cardiomyopathy

Abstract Background Hemodynamic force (HDF) analysis allows non-invasive measurement of intraventricular pressure gradients, portraying cyclic spatial-temporal interaction between blood and tissues. Impaired HDFs have been implicated in early detecting of adverse cardiac remodelling and treatment response in various cardiovascular disorders, providing insights into cardiac physiology not offered by traditional cardiovascular imaging (1). Mainly explored in heart failure, HDF analysis has not been previously applied to hypertrophic cardiomyopathy (HCM). Purpose To investigate differences in systo-diastolic function in HCM patients compared to healthy controls using HDF analysis. Methods Forty patients with HCM diagnosis (20 obstructive and 20 non-obstructive) were retrospectively evaluated in comparison with 22 healthy controls. Left ventricular (LV) HDFs were derived from routine transthoracic apical 4-, 2- and 3-chamber views using a dedicated software. Apical-basal HDF curves were generated, where positive deflections represent forces directed from the LV apex to the base, whilst negative ones are directed toward the apex. Amplitude and timing parameters were derived, the latter indexed to total cardiac cycle duration. Results Table 1 shows the demographic, clinical and echocardiographic characteristics of HCM compared to controls. Patients with HCM were older, had a slower heart rate due to treatment with beta-blockers, and showed hypercontractility, as expressed by higher LV ejection fraction. Compared to controls, HCM patients showed reduced LV longitudinal force, i.e. the force during the whole cardiac cycle (4.17% [2.36-5.52] vs. 6.01% [4.73-7.78], p=0.002), shorter time interval to systolic peak (0.15 [0.12-0.16] vs. 0.19 [0.17-0.20], p &amp;lt;0.001), and shorter duration of LV impulse (0.29 [0.27-0.32] vs. 0.34 [0.32-0.37], p &amp;lt;0.001) (Figure 1). However, no differences in terms of systolic force peak (p=0.283) or LV impulse intensity (p=0.689) were detected. During the transition between systole and diastole, LV suction (i.e. the interval including late systolic deceleration and early diastolic suction) was significantly longer (0.26 [0.22-0.29] vs. 0.23 [0.21-0.25], p=0.023) but less pronounced (6.30% [4.56-8.44] vs. 8.72% [6.71-12.59], p=0.005), likely reflecting a relaxation impairment from the very beginning of diastole. Such impairment was maintained during early diastolic filling, where the amplitude of the positive deceleration flow force was severely reduced in HCM compared to controls (2.98% [1.98-4.58] vs. 7.11% [4.55-8.72], p &amp;lt;0.001). Conclusions HDF analysis in HCM patients revealed unique systolic and diastolic changes reflecting faster LV contraction during systole and slower and weaker LV forces during diastole. This analysis deepens our understanding of HCM mechanic abnormalities and may help assess response to innovative treatment options.

Utilizing unsupervised machine learning to uncover novel phenogroups within the broad QRS complex

Abstract Background Conduction disease can manifest as a broad QRS complex on the ECG. Broad QRS is conventionally categorised as left bundle branch block (LBBB) and right bundle branch block (RBBB) or non-specific intraventricular conduction delay (IVCD), based on QRS morphology. These subgroups were coined over a century ago and have been relevant for heart failure with reduced ejection fraction and cardiac resynchronization therapy (CRT). However, there may be more precise phenogroups underlying broad QRS complexes. Purpose Using unsupervised machine learning to define novel broad QRS phenogroups and characterise them using clinical variables and disease outcomes. Methods We extracted 51 relevant features using a Variational Autoencoder from 47,456 median-beat ECGs with broad QRS intervals (QRS ≥ 130ms) from a secondary care cohort. These were input into Discriminative Dimensionality Reduction via Learning a Tree (DDRTree), a clustering method that models the continuum of heterogeneity by projecting the underlying distribution as a tree structure in a low-dimensional space, while assigning distinct branch/cluster labels. Results Six distinct phenogroups were identified within broad QRS morphologies (Figure-1). Two branches were RBBB dominant (Branch 1: more males, high-comorbidity; Branch 6: low-comorbidity/healthy-RBBB). Two branches were LBBB dominant (Branch 4: mixed IVCD with CHB burden; Branch 5: more females, CRT responders). Two branches were IVCD/mixed-phenotype (Branch 2: IVCD-dominant, high risk of future cardiovascular events; Branch 3: average/core branch). Within LBBB, Branch 4 and 5 showed similar trends with improving echocardiography profiles and CRT response when adjusted for covariates, each compared against the core branch. Branch 5 was distinct due its high risk of future HF (HR 1.19 [1.07-1.33] p &amp;lt; 0.01), cardiovascular death (HR 1.35 [1.20-1.50] p &amp;lt; 0.0001), all-cause mortality (HR 1.08 [1.01-1.16] p &amp;lt; 0.05) and CHB (HR 1.35 [1.16-1.56] p &amp;lt; 0.0001) (Figure-2). Conversely within RBBB, Branch 1 and 6 showed stark differences across various traits. Branch 1 captured a high-risk profile associated to higher risk of cardiovascular death (HR 1.37 [1.24-1.52] p &amp;lt; 0.0001), all-cause mortality (HR 1.20 [1.12-1.29] p &amp;lt; 0.0001) and CHB (HR 1.15 [1.01-1.32] p &amp;lt; 0.05) (Figure-2), while Branch 6 retained a low-risk phenotype. The tree dimensions also revealed relevant trends in cardiac anatomy and valvular dysfunction; the top-left region in Figure-1 associated with higher left ventricular ejection fraction and lower left ventricular end-diastolic dimension, lower left ventricular end-systolic dimension and a greater CRT response. Conclusion Through unsupervised methods we have identified conduction disease phenogroups with additive value for disease prognosis and CRT response prediction beyond traditional LBBB and RBBB labels. These novel phenogroups may help guide precision care for patients with a broad QRS complex.Figure-1Figure-2

Real-life impact of complete revascularization of non-ST elevation myocardial infarction during index hospitalization

Abstract Introduction patients with non-ST elevation acute myocardial infarction (NSTEMI) frequently present multivessel disease (MVD) with significant stenosis in non-infarct-related arteries (non-IRA). Unlike for ST elevation acute myocardial infarction, there is a paucity of studies evaluating the prognostic impact of complete revascularization in these patients. In fact, recommendation for complete revascularization is based in observational and non-randomized studies suggesting a possible benefit regarding mortality and major cardiovascular events. Purpose to evaluate the prognostic impact of complete revascularization during the index hospitalization in the Portuguese patients with NSTEMI and MVD. Methods patients hospitalized for NSTEMI with MVD included in a national multicentre retrospective study between October 2010 and December 2022 were divided into two groups: group 1 was submitted to complete percutaneous revascularization during the index hospitalization (IRA and non-IRA with diameter stenosis ≥50% on angiography), and group 2 performed IRA-only revascularization. The impact of complete revascularization on the probability of cardiovascular re-hospitalization, as well as on in-hospital and one-year mortality rates was evaluated. Results a total of 3084 patients was included, 74.8% were males, with a mean age of 67.8±11.9 years. Most patients were submitted to IRA-only revascularization (72.9%). From the remaining, 81.4% performed complete revascularization during the index procedure and 18.6% staged during index hospitalization. Group 1 patients were younger (65.5±11.8 vs. 68.6±11.8 years, p&amp;lt;0.001), with fewer comorbidities and slightly higher left ventricular ejection fraction (55±11 vs. 51±11%, p&amp;lt;0.001). On the other hand, group 2 patients revealed a significantly higher percentage of previous, revascularization (14.8% vs. 1.6%), mostly surgical. Besides overall similar incidence of in-hospital complications, including recurrence of acute myocardial infarction, patients submitted to complete revascularization showed a non-significant trend to an inferior in-hospital mortality rate (0.7 vs. 1.6%, p=0.06). Also, 1-year mortality rate was similar between groups (4.2 vs. 5.0%, p=0.54). However, complete revascularization appeared to result in a long-term prognostic benefit, halving the incidence of unplanned cardiovascular re-hospitalizations at one year of follow-up (9.3 vs. 18.8%, p&amp;lt;0.001). Conclusion complete revascularization led to an overall long-term benefit, mainly due to a reduction in cardiovascular re-hospitalizations, without a significant impact on 1-year mortality rate.

Residual mitral leaflet length independently indicates left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Abstract Background Due to its dynamic character, the diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive exercise testing. Mitral valve alterations represent structural parameters that are not affected by load or contractility and influence left ventricular outflow tract (LVOT) gradients. The residual portion of the mitral valve extending past its coaptation (RML) has been postulated as a necessity to exhibit LVOTO. Purpose This study aims to assess the impact of RML length on the likelihood of LVOTO in HCM patients. Methods This is a cross-sectional, multi-center, registry-based analysis conducted at two HCM referral centers. The study included HCM patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses. LVOTO was defined as resting or dynamic peak LVOT gradients ≥30 mmHg. Results Among 270 HCM patients studied (43% women, mean age 58±14 years), 131 patients (49%) exhibited LVOTO, with 76 (28%) having undergone septal reduction therapy (SRT). Patients with obstructive HCM exhibited a more pronounced end-diastolic interventricular septum (IVSd) thickness (2.2±0.4 vs. 1.8±0.5 cm; p&amp;lt;0.001) and higher left ventricular ejection fraction (LVEF) (65±9 vs. 62±10%; p=0.009) compared to those without LVOTO (nHCM). Obstructive HCM patients demonstrated longer anterior (29±4 vs. 26±4 mm; p&amp;lt;0.001), posterior (23±4 vs. 20±4 mm; p&amp;lt;0.001), and residual mitral leaflets (11±3 vs. 7±3 mm; p&amp;lt;0.001) than nHCM patients. Multivariable logistic regression analysis adjusting for age, IVSd thickness, LVEF, anterior, and posterior mitral leaflet length identified RML length as an independent predictor of LVOTO [OR=1.47 (95% CI 1.30-1.66); p&amp;lt;0.001]. The area under the receiver-operating characteristic curve for RML length in identifying LVOTO was 0.82 (95% CI 0.77-0.87). RML length ≥9 mm demonstrated 73% sensitivity and 77% specificity in identifying obstructive HCM patients. Notably, these results remained statistically significant in sensitivity analyses selectively performed in HCM patients who had previously undergone SRT as well as in those who were SRT-naïve, respectively. Conclusions This study indicates RML length as an independent predictor of LVOTO in HCM patients. Moreover, RML length demonstrated high diagnostic accuracy in identifying LVOTO among HCM patients. Prospective studies are warranted to assess the added value of RML length in the diagnostic work-up of HCM patients.Figure:Diagnostic Accuracy of RML

Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction

Abstract Background More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials. Purpose The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF. Methods This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) &amp;lt; 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation. Results Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p&amp;lt;0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p&amp;lt;0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p&amp;lt;0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p&amp;lt;0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p&amp;lt;0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function. Conclusion Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.

All-cause mortality and incidence of appropriate therapy from a primary preventive implantable cardioverter defibrillator in patients with non-ischemic dilated cardiomyopathy

Abstract Background The DANISH study published in 2016 indicated limited benefit of primary prevention implantable cardioverter-defibrillator (ICD) in patients with non-ischemic dilated cardiomyopathy (niDCM). We aimed to investigate the long-term outcome and incidence of ICD therapy in patients with niDCM implanted on primary prevention indication during 2014-2022. Methods A total of 116 patients with niDCM were prospectively included for primary prevention ICD implantation between 2014 and 2022 in the multicenter IMPROVE study (clinical trials NCT02286908). All patients were examined with electrocardiogram, echocardiography and blood sampling at inclusion. The primary outcome was all-cause mortality, and the secondary outcome was appropriate ICD therapy. Outcomes were compared in patients included from 2014 to end of 2016 (DCM2014-16, n=49) and from 2017-2022 (DCM2017-22, n=67). Results At inclusion, patients in DCM2017-22 were younger (54 years [interquartile range (IQR) 44-68] vs. 64 years [IQR 55-70], p=0.001), had higher left ventricular ejection fraction (LVEF) (33% [IQR 25-38] vs. 24% [IQR 21-31], p&amp;lt;0.001) and less frequently received cardiac-resynchronization therapy defibrillator (6% vs. 29%, p=0.001) compared to DCM2014-16. Over a median 4.4-year follow-up, the all-cause mortality was 14%, of which 10% occurred in the DCM2017-22 patients (2.6 events/100 person-years), and 18% in the DCM2014-16 patients (4.0 events/100 person-years), p=0.38. There was no difference in appropriate ICD therapy between the two groups (p=0.90). Conclusion Patients receiving primary prevention ICD for niDCM after publication of the DANISH study were younger with higher LVEF, indicating a change in clinical practice after the publication. Despite this, there was no significant reduction in all-cause mortality or difference in appropriate ICD therapies. Unchanged mortality and event-rates may indicate the correct identification of high-risk patients.

Sex differences in diastolic function following myocardial infarction on doppler echocardiography

Abstract Background Whilst females have relatively greater preservation of left ventricular ejection fraction (LVEF) following myocardial infarction (MI), they have higher rates of heart failure, presumably due to diastolic dysfunction (DD). Objectives This study sought to assess sex differences in LV diastolic function on Doppler echocardiography following MI. Methods Data on 2505 consecutive patients with a first-ever MI were included. Echocardiography was performed within 24 hours of admission. Significant DD was defined as grade 2+3 DD according to current ASE/EACVI guidelines. Diastolic function score (DFS) was calculated by summing the number of abnormal parameters out of the 4 key diastolic parameters (e’ velocity, E/e’ ratio, left atrial volume index [LAVI], tricuspid regurgitation velocity [TRV]). Results Compared to males, females were older, had greater co-morbidity, less 3-vessel disease, and a higher LVEF (55.0+9.8% versus 52.7±9.8%, p&amp;lt;0.001). LAVI, e’ velocity, E/e’ ratio, significant DD and DFS were significantly associated with female sex on univariate group comparisons. In multivariable models incorporating clinical, angiographic and echocardiographic data to determine independent predictors of diastolic parameters, female sex was independently associated with abnormal LAVI (OR 1.42, p=0.013), E/e’ ratio (OR 2.86, p&amp;lt;0.001), TRV (OR 1.83, p=0.005), significant DD (OR 2.12, p&amp;lt;0.001) and DFS (OR 2.60, p&amp;lt;0.001). Conclusions Female sex is a strong independent correlate of diastolic dysfunction on Doppler echocardiography in patients with a first-ever MI. This may explain the higher incidence of heart failure despite relatively preserved LVEF in females following MI.

Association of left ventricular ejection fraction with risk of cardiovascular diseases: a prospective cohort study

Left ventricular ejection fraction (LVEF) is the most ubiquitous parameter in cardiac imaging examinations, we aimed to investigate the associations between subtle changes of LVEF and risk of common cardiovascular diseases. This is a prospective cohort study based on UK Biobank. LVEF was obtained from cardiac magnetic resonance. Incident cardiovascular disease was the outcome, including heart failure, atrial fibrillation, ischemic heart disease, and myocardial infarction. Cox proportional hazard model was the main method. A U-shaped relationship was observed between quantified LVEF and cardiovascular events risk with the nadir at the LVEF of 55–64%. As compared to moderate LVEF (55–64%), both low (40–54%) and high LVEF ( ≥ 5%) were related to higher risk of cardiovascular diseases after adjusting for confounders (HRlow = 1.15, 95%CI = 1.02–1.30; HRhigh = 1.34, 95%CI = 1.05–1.72). Specifically, low LVEF was associated with increased risk of heart failure while high LVEF predominantly predicted elevated risk of ischemic heart diseases, both low and high LVEF were related to a borderline higher incidence of atrial fibrillation. Besides, associations with specific cardiovascular diseases varied by age, sex or comorbidities. There was a U-shaped relationship between LVEF and cardiovascular events risk with the nadir at the LVEF of 55–64%, while these associations were disease-specific and varied by age, sex or comorbidities.

Subsequent pregnancies in peripartum cardiomyopathy: Patient-level differences and decision-making

Study objectiveTo evaluate patient-level differences and decision making surrounding subsequent pregnancies (SSP) after peripartum cardiomyopathy (PPCM). DesignMixed methods approach to evaluate quantitative demographic and clinical differences between patients with and without a SSP and to qualitatively describe the decision-making regarding a SSP with a survey component. Setting/participants220 PPCM cases within the University of Pennsylvania Health System. Main outcome measuresDemographic, clinical and obstetrical outcomes. Results73 patients (33 %) had a SSP, 37 with a live birth. Those with a SSP were more likely to self-identify as Black (70 % vs. 52 %; p = 0.04), be nulliparous in index pregnancy (68 % vs. 45 %, p = 0.02), were younger at diagnosis (24.3 vs. 30.5 years; p < 0.01), and a higher left ventricular ejection fraction (LVEF) at diagnosis (35 % vs. 27.5 %; p = 0.03) compared to patients without a SSP. There was no difference in recovery rates of LVEF (62 % vs. 50 %, p = 0.17), or need for LVAD, transplant, or death. 22 patients completed the survey (representing 44 SSPs): 41 % of SSPs (n = 18) resulted in termination, 18 % (n = 8) in a first/s trimester loss, and 41 % (n = 18) in a live-born delivery. All patients who elected termination indicated risk of recurrence/worsening heart failure to be a motivating factor. ConclusionsLess than 20 % of patients in this single-center, multi-racial cohort had a SSP and delivery after PPCM with fear of recurrence as a large driver in this decision. Patients with a SSP were younger with a higher EF at diagnosis but ultimately had similar cardiac outcomes as patients without a SSP.

Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure with Mildly Reduced and Preserved Ejection Fraction: a Prespecified Analysis of The FINEARTS-HF Trial.

The effect of treatments for heart failure may vary among patients according to left ventricular ejection fraction (LVEF). In the FINEARTS-HF, the nonsteroidal MRA finerenone reduced the risk of cardiovascular death and total worsening heart failure events in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). We examined the effect of finerenone according to LVEF in FINEARTS-HF. FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with heart failure and LVEF &#x226540%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (<50%, ≥50 to <60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53 ± 8% and 53% (IQR 46% -58%), respectively. LVEF was <50% in 2172 (36), between 50 to <60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with a higher LVEF were older, more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared to those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total heart failure events consistently across LVEF categories: LVEF <50% rate ratio (RR) = 0.84 (95% CI 0.68, 1.03), LVEF ≥50 to <60% RR = 0.80 (0.66, 0.97) and LVEF ≥60% RR = 0.94 (0.70, 1.25); p interaction = 0.70. There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable (p interaction = 0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening heart failure events (continuous p interaction = 0.26). In patients with HFmrEF/HFpEF, finerenone reduced the risk of cardiovascular death and worsening heart failure events, irrespective of LVEF.

Risk Stratification in Nonischemic Dilated Cardiomyopathy Using CMR Imaging

Accurate risk stratification of nonischemic dilated cardiomyopathy (NIDCM) remains challenging. To evaluate the association of cardiac magnetic resonance (CMR) imaging-derived measurements with clinical outcomes in NIDCM. MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection databases were systematically searched for articles from January 2005 to April 2023. Prospective and retrospective nonrandomized diagnostic studies reporting on the association between CMR imaging-derived measurements and adverse clinical outcomes in NIDCM were deemed eligible. Prespecified items related to patient population, CMR imaging measurements, and clinical outcomes were extracted at the study level by 2 independent reviewers. Random-effects models were fitted using restricted maximum likelihood estimation and the method of Hartung, Knapp, Sidik, and Jonkman. All-cause mortality, cardiovascular mortality, arrhythmic events, heart failure events, and major adverse cardiac events (MACE). A total of 103 studies including 29 687 patients with NIDCM were analyzed. Late gadolinium enhancement (LGE) presence and extent (per 1%) were associated with higher all-cause mortality (hazard ratio [HR], 1.81 [95% CI, 1.60-2.04]; P < .001 and HR, 1.07 [95% CI, 1.02-1.12]; P = .02, respectively), cardiovascular mortality (HR, 2.43 [95% CI, 2.13-2.78]; P < .001 and HR, 1.15 [95% CI, 1.07-1.24]; P = .01), arrhythmic events (HR, 2.69 [95% CI, 2.20-3.30]; P < .001 and HR, 1.07 [95% CI, 1.03-1.12]; P = .004) and heart failure events (HR, 1.98 [95% CI, 1.73-2.27]; P < .001 and HR, 1.06 [95% CI, 1.01-1.10]; P = .02). Left ventricular ejection fraction (LVEF) (per 1%) was not associated with all-cause mortality (HR, 0.99 [95% CI, 0.97-1.02]; P = .47), cardiovascular mortality (HR, 0.97 [95% CI, 0.94-1.00]; P = .05), or arrhythmic outcomes (HR, 0.99 [95% CI, 0.97-1.01]; P = .34). Lower risks for heart failure events (HR, 0.97 [95% CI, 0.95-0.98]; P = .002) and MACE (HR, 0.98 [95% CI, 0.96-0.99]; P < .001) were observed with higher LVEF. Higher native T1 relaxation times (per 10 ms) were associated with arrhythmic events (HR, 1.07 [95% CI, 1.01-1.14]; P = .04) and MACE (HR, 1.06 [95% CI, 1.01-1.11]; P = .03). Global longitudinal strain (GLS) (per 1%) was not associated with heart failure events (HR, 1.06 [95% CI, 0.95-1.18]; P = .15) or MACE (HR, 1.03 [95% CI, 0.94-1.14]; P = .43). Limited data precluded definitive analysis for native T1 relaxation times, GLS, and extracellular volume fraction (ECV) with respect to mortality outcomes. The presence and extent of LGE were associated with various adverse clinical outcomes, whereas LVEF was not significantly associated with mortality and arrhythmic end points in NIDCM. Risk stratification using native T1 relaxation times, extracellular volume fraction, and global longitudinal strain requires further evaluation.

Association between pre-arrest left ventricular ejection fraction and survival in nontraumatic out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) poses major public health issues. Pre-arrest heart function is a prognostic factor, but the specific contribution of pre-arrest echocardiographic evaluation in predicting OHCA outcome remains limited. The primary objective was to investigate the association between left ventricular ejection fraction (LVEF) measured in echocardiography prior to OHCA and survival to hospital discharge. This multicenter retrospective cohort study analyzed data from the National Taiwan University Hospital and its affiliated hospitals. We included adult nontraumatic OHCA patients who were treated by the emergency medical services (EMS) and underwent echocardiography within 6 months prior to the OHCA event from January 2016 to December 2022. Data included demographics, preexisting diseases, resuscitation events, and echocardiographic reports. The primary outcome was the survival to hospital discharge after post-arrest care. Statistical analysis involved multivariable logistic regression to modify potential confounders, reported as adjusted odds ratio (aOR) and 95% confidence interval (CI), and evaluate the association between echocardiographic findings and survival to hospital discharge. This study analyzed 950 patients, with 33.6% surviving to discharge. A higher pre-arrest LVEF was independently associated with increased survival. Compared to patients with LVEF < 40%, those with LVEF between 40% and 60% had significantly higher odds of survival (aOR = 3.68, 95% CI = 2.14-6.35, P < 0.001), and those with LVEF > 60% had even greater odds of survival (aOR = 5.46, 95% CI = 3.09-9.66, P < 0.001). There was also an association between lower tricuspid regurgitation pressure gradient and survival (aOR = 0.98, 95% CI = 0.97-1.00, P = 0.015). Younger age, male gender, dyslipidemia, stroke, cancer, witnessed arrest, initial shockable rhythm, and shorter low-flow time are other significant predictors of survival. In adult, nontraumatic, EMS-treated OHCA patients, a higher LVEF 6 months prior to OHCA was associated with improved survival at hospital discharge.

Contributors to high left ventricular ejection fraction in women with ischemia and no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation—Coronary Vascular Dysfunction (WISE-CVD) Study

There are sex differences in left ventricular ejection fraction (LVEF) relevant to prognosis where women experience greater mortality at relatively higher LVEF compared to men, yet mechanistic understanding of this adverse prognosis is limited. Women with suspected ischemia with no obstructive coronary disease (INOCA) develop heart failure with preserved ejection fraction (HFpEF), yet contributors to LVEF remain largely unknown. In 370 women with suspected ischemia with no obstructive coronary disease (INOCA) who prospectively underwent cardiac magnetic resonance imaging (CMRI), we investigated the contributions of LV morphology, function, and myocardial perfusion reserve on LVEF using univariate and multiple linear regression. A majority 71% of participants had high LVEF (>65%), followed by 24% having normal LVEF (55%-65%), and only 5% having low EF (<55%). Baseline characteristics were comparable among the 3 groups, with the exception of age which was 6 years higher in the high LVEF group (P < .01). Women in the high LVEF group also had the lowest LV cavity volume, greatest LV mass-volume ratio, and highest LV end-systolic elastance (all P < .05, adjusted for age, BMI, diabetes, and blood pressure). Myocardial perfusion reserve index was low in all groups (mean MPRI < 2.1) but was not significantly different across the spectrum of LVEF (P = .458). Taken together, these data demonstrate that the majority of women with suspected INOCA have elevated LVEF related to smaller, thicker ventricles with greater contractility. Future work is needed to better understand the specific mechanisms driving morphologic and functional changes in women with INOCA, and relations to longer-term HFpEF and mortality. NCT02582021.

Left Ventricular Diastolic Dysfunction in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction and Its Relation to Prognosis

Left Ventricular Diastolic Dysfunction in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction and Its Relation to Prognosis

Prognostic impact of diagnosis-to-ablation time on outcomes following catheter ablation in persistent atrial fibrillation and left ventricular systolic dysfunction

BackgroundThe optimal timing of catheter ablation in individuals with atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) remains uncertain. ObjectiveWe examined whether AF diagnosis to ablation time (DAT) influences outcomes following catheter ablation (CA) in patients with persistent AF (PsAF) and LVSD from the CAMERA-MRI and CAPLA randomized studies. MethodsWe evaluated clinical outcomes according to DAT < 1 year (“shorter DAT”) and ≥1 year (“longer DAT”), comparing AF recurrence, AF burden, left ventricular ejection fraction (LVEF), and LV recovery (LVEF ≥ 50%) at 12 months. DAT was also compared according to the median (24 months). ResultsTwo hundred and ten individuals with AF and LVSD were identified, with a median DAT of 24 months. Shorter DAT was associated with lower LA global and posterior wall scar (<0.05 mV; both P < .05). At 12 months, 69.4% with shorter DAT (<1year) were free from recurrent atrial arrhythmias vs 53.6% in longer DAT (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.01–2.65, P = .040). Median AF burden was 0% in both groups (shorter DAT: interquartile range [IQR] 0.0–2.0% vs longer DAT: IQR 0.0–7.3%, P = .017). At 12 months, shorter DAT was associated with higher LVEF (55.3% vs 51.0%, P = .009), greater LVEF improvement (+20.8 ± 13.0% vs +13.9 ± 13.2% longer DAT, P < .001) and LV recovery (75.0% vs longer DAT: 57.2%, P = .011). Shorter DAT was associated with fewer hospitalizations and electrical cardioversions at 12 months. ConclusionIn individuals with AF and LVSD, shorter DAT was associated with greater LVEF improvement and arrhythmia-free survival with lower AF burden and rehospitalization at 12 months, highlighting the prognostic benefit of early CA in AF and LVSD.