Improvement In Left Ventricular Ejection Fraction Research Articles

Association of BMI with adherence and outcome in heart failure patients treated with wearable cardioverter defibrillator.

Obesity is a known risk factor for cardiovascular disease (CVD), yet an 'obesity paradox' has been observed in various CVD contexts. The impact of obesity on heart failure (HF) patients treated with a wearable cardioverter-defibrillator (WCD) remains underexplored. In a multicentre international registry, we retrospectively collected data from a consecutive series of 1003 patients. These patients were divided into three body mass index (BMI) groups: <25kg/m2 (n=348), 25-30kg/m2 (n=383), and >30kg/m2 (n=272), with BMI>30kg/m2 defined as the reference category. Demographics, indications, adherence, WCD shocks, arrhythmic events, rehospitalization due to cardiovascular causes, and mortality were analysed. At 3month follow-up, patients with a BMI>30 showed the greatest improvement in left ventricular ejection fraction (LVEF) at 51.4%, significantly higher than the 41.4% in those with a BMI<25 (P=0.017) and comparable with the 49.4% in the BMI 25-30 group (P=0.635). WCD wearing time and adherence were similar across all BMI groups. The incidence of WCD shock was similar across BMI groups. Rates of ventricular tachycardia (VT), ventricular fibrillation and non-sustained VT (ns-VT) were comparable across BMI groups. The rate of implantable cardioverter-defibrillator (ICD) implantation was 40.3% across all patients, with a slightly lower rate in the BMI>30 group (36.8%) compared with others, although not significantly. Rehospitalization due to cardiovascular causes was significantly lower in the BMI>30 group (55.4%) compared with the BMI 25-30 group (70.9%; P=0.048), but similar to the BMI<25 group (54.9%; P=0.957). At 2year follow-up, mortality was lower in the BMI>30 group (5.9%) compared with the BMI<25 (7.5%; P=0.029) and BMI 25-30 groups (7%; P=0.681). In multivariable analysis, LVEF at long term was significantly associated with a reduction in mortality. Obese patients exhibited significantly greater improvement in LVEF, which was associated with reduced mortality. Adherence to WCD therapy was excellent across all BMI groups. ICD implantation occurred in 40.3% of patients, with similar WCD shock rates and arrhythmic events across BMI groups. An obesity paradox was observed, with obese patients demonstrating significantly lower rehospitalization rates due to cardiovascular causes and reduced mortality at follow-up.

Sacubitril-Valsartan Lowers Atrial Fibrillation Recurrence and Left Atrial Volume Post-catheter Ablation: Systematic Review and Meta-Analysis.

In patients with atrial fibrillation (AF) who have undergone catheter ablation, the comparative effectiveness of sacubitril-valsartan (SV) versus ACE inhibitors (ACEi) or angiotensin-receptor blockers (ARB) in preventing AF recurrence remains unclear. The purpose of the present systematic review and meta-analysis is to determine whether SV offers superior outcomes in this clinical setting. This study systematically reviewed PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and propensity-matched cohorts (PMC), evaluating SV's efficacy in preventing AF recurrence after catheter ablation. Outcomes included AF recurrence and structural remodeling assessed via left ventricular ejection fraction (LVEF) and left atrial volume index (LAVi), with statistical analyses performed using Review Manager 5.1.7 and heterogeneity assessed via I2 statistics. The analysis comprised 642 patients from three RCTs and one PMC (319 SV-treated). SV significantly reduced AF recurrence [risk ratios (RR) 0.54; 95% confidence intervals (CI) 0.41-0.70; p < 0.00001; I2 = 0%), a trend also observed when considering RCTs exclusively (RR 0.58; 95% CI 0.41-0.84; p = 0.004; I2 = 0%). Moreover, SV demonstrated a notable reduction in LAVi [mean deviation (MD) -5.34 mL/m2; 95% CI -8.77 to -1.91; p = 0.002; I2 = 57%] compared with ARB, alongside a significant improvement in LVEF (MD 1.83%; 95% CI 1.35-2.32; p < 0.00001; I2 = 0%). Subgroup analyses among patients with hypertension and LVEF < 50% also indicated lower AF recurrence with SV. SV therapy exhibited superior efficacy in reducing AF recurrence compared with ACEi or ARB and demonstrated superior outcomes in attenuating atrial structural remodeling after catheter ablation. These findings underscore the potential of SV as a therapeutic option for patients with AF undergoing catheter ablation, highlighting its efficacy in mitigating AF recurrence and structural remodeling. PROSPERO identifier number CRD42024497958.

Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy

Abstract Introduction Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients. Purpose This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients. Methods Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90). Results After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR &amp;gt; median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p&amp;lt;0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B). Conclusion Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.

Association of left ventricular ejection fraction improvement with prognosis in patients with cardiac sarcoidosis: insights from the ILLUMINATE-CS study

Abstract Introduction While the beneficial impact of enhancing left ventricular ejection fraction (LVEF) is well-documented in patients with heart failure with reduced LVEF, its relevance in cardiac sarcoidosis (CS) remains unclear. Purpose This study aimed to identify predictive factors for LVEF improvement and explore its association with prognosis in patients with CS. Methods A post-hoc analysis of the ILLUMINATE-CS registry, a retrospective observational study across multiple centers, was conducted. CS diagnosis adhered to either the 2016 Japanese Circulation Society guidelines or the 2014 Heart Rhythm Society expert consensus statement. Patients with baseline LVEF ≥50% were excluded in the current analysis. LVEF improvement was quantified as the variance between baseline and follow-up echocardiography. Patients were categorized into tertiles based on LVEF improvement: 1st tertile (≤0%, least improved), 2nd tertile (0–9%), and 3rd tertile (&amp;gt;9%, most improved) groups. The primary outcome was all-cause mortality after follow-up echocardiography. Results Among 188 enrolled patients (mean age 62.1±10.7 years; 42.6% male), 65, 60, and 63 were allocated to the 1st, 2nd, and 3rd tertile groups, respectively. Multivariate linear regression analysis revealed that narrower QRS duration, lower baseline LVEF, and absence of beta-blocker prescription at baseline were independently associated with greater LVEF improvement. Over a median follow-up of 407 days, 26 all-cause deaths occurred. Kaplan–Meier curves exhibited significant difference among the tertile groups (log-rank, P=0.002). Cox proportional hazard analysis, adjusted for possible prognostic factors including LVEF, demonstrated significantly higher mortality in the 1st and 2nd tertile groups compared to the 3rd tertile group (vs. 1st tertile: hazard ratio [HR] 22.14, 95% confidence interval [CI] 2.73–179.50, P=0.004; vs. 2nd tertile: HR 8.17, 95% CI 1.02–65.71, P=0.048). Additionally, treating LVEF improvement as a continuous variable revealed an independent association with increased mortality (LVEF improvement per 5%: HR 0.69, 95% CI 0.54–0.87, P=0.002). Conclusions Improvement LVEF in patients with CS is significantly associated with improved outcomes, highlighting its clinical importance in managing CS.Kaplan–Meier curves for all-cause death

LVEF trajectory in HFimpEF and its association with prognosis

Abstract Background The 2021 revised Universal Definition of Heart Failure (HF) introduced the subgroup known as HF with improved ejection fraction (HFimpEF), aiming to establish a standardized definition for left ventricular ejection fraction (LVEF) improvement and emphasize the importance of longitudinally assessment of LVEF. However, there remains an insufficient characterization of the association between serial LVEF trajectory before and after impEF, and outcomes in HFimpEF. Purpose We aim to delineate the LVEF trajectory in patients with impEF and to discern specific LVEF trajectory pattern that portends an unfavorable prognosis. Methods We conducted a retrospective analysis by including hospitalized HF patients with baseline LVEF ≤ 40% and satisfactory serial echocardiographic follow-ups. ImpEF was defined as a follow-up LVEF measurement of &amp;gt; 40% with a ≥10-point increase from baseline. Longitudinal LVEF trajectories for patients with impEF (before and after LVEF improvement) were plotted according to the clinical outcome of all-cause death using Loess curves. LVEF changes over time were analyzed by unconditional non-linear mixed-effects modeling, and compared between the groups of patients who died and those who survived using conditional non-linear mixed-effects modeling. Results Among the initial 923 patients with reduced LVEF, 517 had impEF. According to Loess curves and non-linear mixed-effects analysis, LVEF trajectory of impEF differed according to the clinical outcome of death. For patients who suffered all-cause death, there was a comparatively limited improvement in LVEF followed by a more rapid plateauing and decline, exhibiting an inverted U-shaped pattern with lower LVEF values towards both ends of the distribution. Conclusions In HFimpEF, an inverted U-shaped trajectory of LVEF, characterized by limited initial improvement followed by subsequent decline, is associated with poorer prognosis. Serial LVEF monitoring in patients with HFimpEF could help with early identification of at-risk patients.Graphical Abstract

Sinus rhythm restoration as an independent predictor of left ventricular ejection fraction improvement in patients with the first hospitalization for heart failure and reduced ejection fraction

Abstract Background and Purpose Tachycardiomyopathy (TCM) is prevalent in heart failure with reduced ejection fraction (HFrEF). Despite its significance, a comprehensive understanding of its evolutionary trajectory and prognosis remains limited. This study aims to investigate the prognosis and left ventricular ejection fraction (LVEF) trajectory in patients with TCM compared to other etiologies within a cohort initially admitted for "de novo" HFrEF (LVEF &amp;lt; 40%). Methods A prospective registry was conducted across two University Hospitals, incorporating patients hospitalized with a diagnosis of HFrEF. The study encompassed 370 patients admitted between March 2021 and October 2023, with a median follow-up of 15 months (IQR 7-22). Two distinct groups were delineated based on etiology (TCM vs other etiologies). Within the TCM cohort, subgroups were established concerning LVEF improvement, following the criteria outlined in the "Universal Definition and Classification of Heart Failure" report. Categorical variables were presented as absolute frequencies and percentages, analyzed using the chi-square test. Continuous variables were expressed as mean +/- SD and compared through Student's t-test or Mann-Whitney U test. Hazard functions were estimated using the Kaplan-Meier method. Data analysis was executed using SPSS Statistics. Results In our cohort, both TCM and other etiologies groups exhibited improved LVEF post-neurohumoral blockage titration. Nonetheless, the TCM cohort demonstrated notably higher LVEF (49.1% vs. 43.5%, p = 0.005) [Figure 1]. Moreover, overall mortality, cardiovascular mortality, and the composite of CV mortality and hospitalizations for CV causes were notably lower in the TCM group compared to other etiologies [Figure 2]. Among TCM patients, those with improved LVEF during follow-up were younger (66 vs. 72), with no differences in treatment at discharge or after neurohumoral blockage titration. While achieving sinus rhythm before discharge did not correlate with LVEF improvement, attaining sinus rhythm during follow-up (at titration completion) significantly correlated with LVEF improvement [Table 1]. Multivariate analysis revealed that sinus rhythm restoration after up-titration emerged as an independent predictor of LVEF improvement, irrespective of sinus rhythm restoration at discharge or the attainment of quadruple therapy during follow-up, among other variables (Table 2). Conclusions Among patients initially admitted for "de novo" HFrEF, TCM presents a potentially more favorable clinical trajectory compared to other HF causes, showcasing reduced total and cardiovascular mortality, as well as combined cardiovascular mortality and hospitalizations for cardiovascular causes. Notably, in this patient subset, sinus rhythm restoration during follow-up emerged as an independent predictor of improved LVEF, irrespective of pre-discharge sinus rhythm restoration or adherence to comprehensive four-pillar HF management.

Prognostic impact of left ventricular ejection fraction improvement after transcatheter aortic valve replacement

Abstract Introduction Transcatheter aortic valve replacement (TAVR) has become an efficient and save alternative to surgical aortic valve replacement (SAVR). While severe aortic stenosis as well as severe aortic regurgitation (AR) is known to negatively impact left ventricular ejection fraction (LVEF), prior studies have shown that TAVR can lead to improvement in LVEF. So far, little is known about the prognostic implication of LVEF-improvement as a sole predictor of outcomes. Purpose The aim of this study was to assess the prognostic significance of early LVEF improvement in patients undergoing TAVR. Materials and Methods Patients undergoing TAVR in a large tertiary university hospital have been consecutively included in a large prospective registry. Transthoracic echocardiography (TTE) was performed at baseline, after TAVR before discharge, at 1 month and annually thereafter. Significant LVEF improvement was defined as &amp;gt;10% relative increase of LVEF at 30 days compared to baseline LVEF. Primary outcome was all-cause mortality at 5 years. Secondary outcome were major adverse cardiovascular events (MACE), including death, non-fatal myocardial infarction, stroke, bleeding and unplanned re-interventions of the aortic valve. Results Among 1481 patients undergoing TAVR between September 2011 and June 2023, LVEF at baseline and at 30 days was available in 1013 patients. 665 patients (65.6%) had normal LVEF at baseline, whereas 348 patients (34.4%) had a reduced LVEF. Of these, 137 patients (13.5%) showed significant improvement of LVEF ≥10%) after 30 days, while 266 patients (26.3%) showed no significant LVEF-improvement (&amp;lt;10%). The combined patients with persevered LVEF at baseline had significantly better outcomes than those with impaired EF (p=&amp;lt;0.001). LVEF improvement was not associated with mortality at 5 years (p= 0.51), however with lower MACE rate at 5 years (p=0,024). Conclusion Normal LVEF before TAVR is an independent predictor for improved outcomes. In addition, early improvement of LVEF is associated with beneficial outcomes in patients undergoing TAVR.Course of LVEF after TAVROutcomes after TAVR

Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis

Abstract Background Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure. Methods A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs). Results A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P&amp;lt;0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P&amp;lt;0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P&amp;lt;0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P&amp;lt;0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P&amp;lt;0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P&amp;lt;0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P&amp;lt;0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P&amp;lt;0.24). Conclusion Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots

Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up

Abstract Introduction Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce. Purpose This study aims to assess long-term outcome in HFrEF patients who underwent BAT. Methods Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups. Results 23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p&amp;lt;0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time. Conclusion BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time

Beating the clock: the impact of heart failure duration on CRT efficacy

Abstract Background Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1 Purpose The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy). Methods We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%). Results The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1). The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p &amp;lt;0.001. Conclusions Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.

Effects of empagliflozin on cardio-renal interaction in heart failure with reduced ejection fraction: results from in-vivo experiments and the CINNAMON-study

Abstract Background Heart failure is often accompanied by renal dysfunction, which indicates a pathophysiological connection between the heart and kidneys. Empagliflozin, a SGLT2 inhibitor, showed beneficial effects on both cardiovascular and renal endpoints. Mechanistically, however, it is unclear whether the empagliflozin-dependent renal protection is mediated via the inhibition of renal SGLT2 or rather indirectly via improved cardiac function. Interestingly, in the EMPEROR trials, there was a significant interaction of empagliflozin-dependent kidney protection with systolic contractile dysfunction. We hypothesized that Empagliflozin treatment ameliorates heart failure in response to chronic pressure overload in mice leading to improved renal function. We correlated these findings with data from our prospective, single-armed trial. Methods Transverse aortic constriction (TAC) or sham surgery was performed in C57BL/6J (wildtype, WT) and SGLT2 deficient mice (SGLT2-/-). Animals received either Empagliflozin (10 mg/kg bodyweight) or vehicle by daily oral gavage. Cardiac function was evaluated by echocardiography and kidney function by transdermal FITC-Sinistrin measurement (GFR), urinary albumin/creatinine ratio (UACR) and Siriusred fibrosis staining. Results After 10 weeks, echocardiography confirmed TAC induced pressure-overload, leading to reduced left ventricular ejection fraction (LVEF) and diastolic dysfunction. Empagliflozin attenuated changes in LVEF (Fig. A) and improved diastolic dysfunction (data not shown). Interestingly, at 10 weeks, TAC reduced GFR, increased UACR and tended to increase renal fibrosis, which was attenuated by empagliflozin (Fig. B, C and D). To test if direct inhibition of SGLT2 in the heart and kidney is mechanistically involved, TAC surgery was repeated in SGLT2-deficient mice (SGLT2-/-). In fact, exposure to TAC resulted in comparable reduction of LVEF in SGLT2-/- mice and Empagliflozin prevented this deterioration similar to WT mice (Fig. E vs. A). Surprisingly, Empagliflozin also prevented GFR deterioration 10 weeks after TAC in mice lacking SGLT2 (SGLT2-/-) with comparable magnitude as in WT mice (Fig. F), suggesting that the reno-protective effect of Empagliflozin was independent from renal SGLT2 inhibition. The effect of empagliflozin on the heart and kidney was also investigated in patients with HF (prospective, single-arm CINNAMON-study, DRKS00031101). After 180 days of Empagliflozin treatment (10 mg), there was a significant improvement in LVEF, NT-proBNP levels and KCCQ-12 Scores (Fig. G-I) and the effects on UACR and GFR are subject of investigation. Conclusion This is the first study investigating the role of SGLT2 in Empagliflozin-dependent kidney protection of mice that develop heart failure after TAC. Importantly, empagliflozin treatment prevented deterioration of LVEF and GFR independent of the presence of SGLT2 in mice and improved cardiac markers and quality of life in patients.

Peak VO2 is associated with cardiac functional response and long-term survival in patients with heart failure and atrial fibrillation undergoing catheter ablation

Abstract Background Contemporary guidelines recommend Catheter Ablation (CA) in patients with persistent Atrial Fibrillation (AF) with Heart Failure with reduced ejection fraction (HFrEF). It is challenging to prospectively predict who will respond. We have previously described the long-term survival outcomes of patients in this cohort.(1) However, the clinical characteristics associated with HF response and long-term clinical outcomes have not been reported. Objective To evaluate the association of HF parameters with cardiac functional response to CA and long-term survival after CA. Methods Post-hoc, long-term follow-up of mortality was undertaken in patients enrolled in the CAMTAF and ARC-HF RCTs. Both studies enrolled patients with persistent AF and HFrEF between 2005 and 2012 and randomised to first-time CA or medical therapy alone. Left ventricular ejection fraction (LVEF) and peak VO2 were measured in both studies at baseline and 12-month follow-up. The Universal Definition of HF response (LVEF improves by &amp;gt;10% points or to an LVEF &amp;gt;50%) was used.(2,3) Multi-variate logistic regression was used to determine features associated with HF response and Cox proportional hazards modelling for survival. Results 102 patients underwent randomisation with 52 assigned to CA. The mean age was 60.2 ±10.7 years with 93 (91.2%) male. The mean Baseline LVEF was 31 ±11% and peak VO2 was 1815 ±642mlmin-1. Baseline LVEF did not correlate significantly with Minnesota Living with Heart Failure (MLWHF) score (r=-0.11, p=0.29) whereas baseline peak VO2 did (r=-0.28, p&amp;lt;0.01). In patients randomised to CA, the median (IQR) improvement in LVEF was +8.4% (0, 15%). 22/52 (42.3%) patients were classified as Responders based on the Universal Criteria. Responders were younger (54.7 ±10.6 years vs 61.8 ±11.4, p=0.03) and had a higher mean HR on baseline Holter monitoring (89 ±14bpm vs 79 ±11bpm p&amp;lt;0.01) than non-responders. There was no significant difference in sex, baseline MLWHF scores, BNP levels or LVEF between groups (28±9% vs 31 ±9%, p=0.19). Responders had a significantly higher peak VO2 at baseline than Non-Responders (1972 ±668mlmin-1 vs 1556 ±580mlmin-1, p=0.03). On multivariate analysis, mean heart rate on Holter monitoring and peak VO2 were significantly associated with Responder status post-ablation. (Table 1a) During a median follow-up of 7.8 (3.9 –9.9) years, 34 (33.3%) patients died, including 17 (32.7%) patients in the CA arm. On univariate analysis, baseline peak VO2 was significantly greater of survivors at 5 years (1867 ±624 mlmin-1 vs 1259 ±497 mlmin-1, p&amp;lt;0.01). On multivariate Cox regression analysis, the peak VO2 at baseline was the only significant predictor of survival (Table 1b). Conclusion Peak VO2 at baseline was associated with baseline symptom status, the short-term LVEF response to CA and long-term survival and may be a useful stratification tool to aid patient selection for CA.1a. Regression for 6-month LVEF response1b. Regression for long-term mortality

Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction

Abstract Introduction Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown. Purpose To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction. Methods We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of &amp;lt;50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data. Results A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p &amp;lt;0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p &amp;lt;0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p &amp;lt;0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p &amp;lt;0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass. Conclusions The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.

Quality of life in patients with heart failure and improved ejection fraction: one-year follow-up with ARNI and SGLT2i

Abstract Introduction A baseline Heart Failure (HF) with reduced Ejection fraction (HFrEF) &amp;lt;=40% that improved for &amp;gt;=10 points and a second measured left ventricle ejection fraction (LVEF) &amp;gt;40%, can be considered as HF with improved ejection fraction (HFimpEF). The novel therapy for HFrEF and HFimpEF are sacubitril/valsartan (ARNI- angiotensin receptor/neprilysin inhibitor) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i). Purpose Our study aimed to evaluate ARNI and SGLT2i therapy on the health status of HFrEF patients, as well as the prognostic impact of HFimpEF in terms of quality of life and outcomes (mortality and rehospitalization due to HF) during a one-year follow-up. Methods In this prospective study, we included 376 hospitalized HFrEF patients, in whom ARNI and SGLT2i were initiated into regular therapy. A 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was performed at discharge and after one year. The primary prognostic endpoints were all-cause mortality and HF rehospitalization. Results Initially, about two-thirds of the study population were men (71%), mean age of 61.0±11.5 years, mean LVEF 27.5±5.2 % and mean KCCQ overall summary (KCCQ-OS) score of 48.5±12.5, while quality of life KCCQ-QoL 37.4±10.2. After one year LVEF was increased by 35.6±7.1 %. The total number of 143 patients (38%) met the criteria for HFimpEF, with the improvement of mean LVEF (45.2±8.6 %., p&amp;lt;0.001). Overall, HFimpEF patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS compared with 2.5 ± 17.4 points for non-HFimpEF group (differences in mean changes of 2.9 [95% CI: 1.4 to 4.7). This is largely due to improvements in the domain of KCCQ-QoL (5.8 ± 29.7 points vs. 2.9 ± 22.2 points, respectively). During one year of follow-up, combined SGLT2i + ARNI therapy was represented statistically significantly more in HFimpEF compared to the non-HFimpEF group (86% vs. 34%, p&amp;lt;0.0005), where 45% took only one medicine and 21% none. The HFimpEF group had a significantly better outcome in terms of all-cause mortality (2.8% vs. 18.9%, p&amp;lt;0.005) and HF rehospitalization (3.5% vs. 40%, p&amp;lt;0.0001). The one-year KCCQ-12 was independently associated with outcomes; the hazard ratio for the integrated endpoints (mortality and HF rehospitalization) was 1.08 (95% CI: 1.05–1.11, p = 0.005). Conclusions In routine clinical practice, initiation of the ARNI and SGLT2i therapy was associated with significant improvements in the health status of HFrEF patients, but also change to HFimpEF. The one-year quality of life in patients with heart failure and improved ejection fraction was superior to baseline and compared to the non-HFimpEF group. HFimpEF was associated with a better outcome. All HF patients should undergo KCCQ-12 because it is an independent predictor of outcome.

Changes in echocardiographic and analytical parameters after iron replacement in stable heart failure patients. FER-STRAIN study

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods We performed an observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin &amp;lt;100 ug/L or between 100 and 300 ug/L if the transferrin saturation was &amp;lt;20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups performed 3D echocardiograms and strain analysis. Analytical parameters and biomarkers were determined basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). In blood tests, a significant improvement of ferritin (130.9±111.98mg/L, p&amp;lt;0.000), hemoglobin (0.3±0.7g/dL, p=0.027) and medium corpuscular volume (1.7±2.16fL, p=0.005), and also an increase of the biomarker myeloperoxidase (40.16±138.36pmol/L, p=0.02) were detected in the treatment group. Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM

Improvement of myocardial contractility after iron replacement in stable heart failure patients

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods Observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin &amp;lt;100 ug/L or between 100 and 300 ug/L if the transferrin saturation was &amp;lt;20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups, performed 3D echocardiograms and strain analysis basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM

Hypoperfused myocardium and systolic function in patients with AMI undergoing complete revascularization

Abstract Background and Aim Coronary revascularization is the standard treatment for acute myocardial infarction (AMI), while the restoration of epicardial flow is non-parallel to myocardial reperfusion. This study sought to investigate the dynamic of myocardial perfusion and its association with left ventricular (LV) systolic function in AMI patients undergoing complete revascularization. Methods AMI patients who underwent complete revascularization were prospectively enrolled, and hybrid positron emission tomography/magnetic resonance (PET/MR) was performed at 2 months and 1 year. Hypoperfused myocardium was defined as myocardium with reduced perfusion and normal metabolism. Results Forty-five patients (59.80 ± 10.68 years, 80.0% male) were enrolled, and hypoperfused myocardium (median: 12% of LV) was detected in 21 (46.7%) patients 2 months post-AMI. Patients with hypoperfused myocardium (Group A) had significantly higher hypersensitive C-reactive protein (hs-CRP) (p = 0.016) and lower T2 value (p = 0.010) than those without (Group B). In the follow-up PET/MR at 1 year, significant LV ejection fraction improvement was observed in Group A (56.39 ± 9.76% vs. 54.58 ± 10.39%, p = 0.016) but not in Group B (51.63 ± 13.09% vs. 50.79 ± 16.95%, p = 0.615). Six (31.6%) patients in Group A showed recovery of perfusion, of which there were more females (p = 0.025), fewer diabetics (p = 0.044), or overweight (p = 0.035), with better global longitudinal strain (GLS) (p = 0.005). Conclusions Myocardial hypoperfusion is not rare and evolves over time in AMI patients undergoing complete revascularization, of which the reversal is probably associated with improved LV systolic function.Structured Graphical AbstractRepresentative PET/MR image of 2 separat

Effects of atrial fibrillation ablation on arrhythmia burden and ventricular function in end-stage heart failure: Lessons from CASTLE-HTx.

The CASTLE-HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end-stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end-stage HF. The CASTLE-HTx protocol randomized 194 patients in end-stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow-up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post-ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6-63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017). Atrial fibrillation ablation in end-stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy.

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial

BackgroundThe therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.MethodsWe conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e’ >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1–7) levels, were also assessed.ResultsA total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (− 15.5 ± 3.1% to − 16.6 ± 2.8%, P = 0.004) compared to the placebo group (− 16.7 ± 2.7% to − 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro–B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1–7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1–7)]. Adverse events were similar between the two groups.ConclusionsThis study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.Clinical trial registration ClinicalTrials.gov Identifier: NCT03717194.

Left Ventricular Ejection Fraction Change Following Percutaneous Coronary Intervention: Correlates and Association With Prognosis.

The association between left ventricular ejection fraction (LVEF) change (ΔLVEF) following percutaneous coronary intervention (PCI) and the long-term mortality rate in patients with coronary artery disease is incompletely investigated. We aimed to assess the impact of PCI on LVEF and the association of ΔLVEF after PCI with the long-term mortality rate. This observational study included 8181 patients with paired angiographic LVEF measurements performed at baseline and 6 to 8 months following the index PCI. ΔLVEF was defined as LVEF measured on the 6- to 8-month angiography minus LVEF measured on the baseline angiography. LVEF change was classified according to the following categories: reduced (ΔLVEF <0), mildly improved (ΔLVEF >0% to <10%) and largely improved (ΔLVEF ≥10%). The primary outcome was the 5-year mortality rate. In patients with baseline LVEF <40%, 40% to <50% and ≥50%, ΔLVEF (median [25th-75th percentiles]) was 6.0% [0.0% to 14.0%], 4.0% [-1.0% to 11.0%] and 0.0% [-4.0% to 3.0%], respectively (P<0.001). In patients with reduced, mildly improved, and largely improved ΔLVEF, the 5-year mortality rate (n=712) was 29.1%, 23.1%, and 16.5%, respectively, in patients with baseline LVEF <40%; 17.0%, 12.2% and 9.8%, respectively, in patients with baseline LVEF 40% to <50%; and 7.8%, 7.1%, and 5.6%, respectively, in patients with baseline LVEF ≥50% (adjusted hazard ratio [HR], 0.91 [95% CI, 0.86-0.96]; P<0.001) for all-cause death and adjusted (HR, 0.86 [95% CI, 0.81-0.92]; P<0.001) for cardiac death, calculated for 5% higher ΔLVEF. In patients with coronary artery disease undergoing PCI, improvement of LVEF following PCI was associated with a reduced long-term mortality rate in patients with reduced LVEF but not in patients with preserved LVEF before intervention.