Clinical Determinants and Prognosis of Left Ventricular Reverse Remodelling in Non-Ischemic Dilated Cardiomyopathy

Aims: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM. Methods: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of ≥15% in left ventricular ejection fraction (LVEF) or as a LVEF increase ≥ 10% plus reduction of LV end-systolic diameter index ≥ 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR. Results: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions. Conclusions: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units.

Epicardial adipose tissue as a mediator of cardiac arrhythmias

Obesity is associated with higher risks of cardiac arrhythmias. Although this may be partly explained by concurrent cardiometabolic ill-health, growing evidence suggests that increasing adiposity independently confers risk for arrhythmias. Amongst fat depots, epicardial adipose tissue (EAT) exhibits a proinflammatory secretome, and given the lack of fascial separation, has been implicated as a transducer of inflammation to the underlying myocardium. The present review explores the mechanisms underpinning adverse electrophysiological remodelling as a consequence of EAT accumulation and the consequent inflammation. We first describe the physiological and pathophysiological function of EAT and its unique secretome, and subsequently discuss the evidence for ionic channel and connexin expression modulation as well as fibrotic remodelling induced by cytokines and free fatty acids that are secreted by EAT. Finally, we highlight how weight reduction and regression of EAT volume may cause reverse remodelling to ameliorate arrhythmic risk.

84 Left atrial reverse remodelling in dilated cardiomyopathy

Aims Left atrial (LA) dilation is associated a with worse prognosis in several cardiovascular settings but therapies can promote LA reverse remodelling. Characterizing and defining the prognostic implications of LA volume (LAVI) reduction in dilated cardiomyopathy (DCM). Methods and results Consecutive DCM patients from two tertiary care centres, with available echocardiography at baseline and at 1 year follow-up, were analysed. LA dilation was defined as LAVI >34 ml/m2, Delta (Δ)LAVI was defined as the 1 year relative LAVI reduction. The outcome was a composite of death/heart transplantation/heart failure hospitalization (D/HTx/HFH). Five hundred sixty patients were included [age 52 ± 13 years; left ventricular ejection fraction (LVEF) 31 ± 10%, LAVI 45 ± 18 ml/m2]. Baseline LAVI had a non-linear association with the risk of D/HTx/HFH, independently from LVEF (P < 0.001). At 1 year follow-up, LAVI decreased in 374 patients (67%, median ΔLAVI 24%, interquartile range 37% 11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline LVEF. After adjustment for confounders, ΔLAVI showed a linear association with the risk of D/HTx/HHF (HR: 0.92, 95% CI: 0.86 0.99 per 5% decrease, P < 0.001). At 1 year Follow-up, patients with a ≥ 15% reduction in ΔLAVI or LAVI normalization (i.e. Follow-up LAVI ≤34ml/m2) (42% of the cohort) were at lower risk of D/HTx/HFH (HR: 0.49, 95% CI: 0.33 0.74, P < 0.001). Conclusions In a large cohort of DCM, 1 year reduction in LAVI is observed in the majority of patients. The association between reduction in LAVI and D/HTx/HHF candidates LA reverse remodelling as complementary early therapeutic goal in DCM.

652 Myocardial work in patients undergoing transcatheter aortic valve implantation: clinical value and implications for outcome

Aims Non-invasive myocardial work (MW) quantification has emerged in the last years as an alternative echocardiographic tool for myocardial function assessment. This new parameter provides a less loading-dependent evaluation of myocardial performance through the combined assessment of global longitudinal strain (GLS) and non-invasive left ventricle (LV) pressures. The role of MW as a marker of cardiac dysfunction and reverse remodelling in patients with severe aortic stenosis (AS) after aortic valve implantation (TAVI) has not been adequately investigated. This study aims to evaluate MW indices as early echocardiographic markers of LV reverse remodelling within a month after TAVI and their prognostic value. Methods and results We conducted a single-centre prospective study, enrolling 70 consecutive patients (mean age 80.1 ± 5.5 years) with severe AS undergoing TAVI between 2018 and 2020, selected from the EffecTAVI registry. Exclusion criteria were prior valve surgery, severe mitral stenosis, permanent atrial fibrillation, left bundle branch block (LBBB) at baseline, and suboptimal quality of speckle-tracking image analysis. Echocardiographic assessment was performed before TAVI and at 30-day follow-up. Clinical, demographic, and resting echocardiographic data were recorded, including quantification of 2D global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). LV peak systolic pressure was estimated non-invasively from the sum of systolic blood pressure and trans-aortic mean gradient. One month after the procedure, there was a significant improvement of LV GLS (−17.94 ± 4.24% vs. −19.35 ± 4.31%, before and after TAVI respectively, P = 0.002), as well as a significant reduction of GWI (2430 ± 586 mmHg% vs. 1908 ± 472 mmHg%, P < 0.001), GCW (2828 ± 626 mmHg% vs. 2206 ± 482 mmHg%, P < 0.001), and GWW (238 ± 207 mmHg% vs. 171 ± 118 mmHg%, P = 0.006). Conversely, MWE did not significantly change early after intervention (90.53 ± 6.05% vs. 91.45 ± 5.05%, P = 0.204). After TAVI, 30 patients (42.8%) developed LV dyssynchrony due to LBBB or pacemaker implantation. When the population was divided according to the presence or absence of LV dyssynchrony at 30-day follow-up, a significant reduction in GWW was found only in those without dyssynchrony (244 ± 241 vs. 141 ± 110 mmHg% with and without dyssynchrony respectively, P = 0.002). Consistently, in this subgroup, MWE significantly improved post-TAVI (90 ± 7 vs. 93 ± 5%, P = 0.002), while a trend of MWE reduction was observed in patients who developed dyssynchrony post-TAVI (91 ± 4 vs. 89 ± 5%, P = 0.164). In the overall population, a baseline value of MWE< 92% was associated with an increased rate of cardiovascular events (composite of all-cause death and rehospitalization for heart failure) at 1-year follow-up (22.2 vs. 3.1%, long rank, P = 0.016). Conclusions In patients with severe AS undergoing TAVI a significant reduction of GWW and improvement of MWE can be detected only in those who did not develop LV dyssynchrony. In this setting, MWE lower than 92% at baseline is associated with poor outcome. Thus, MWE could represent an alternative tool for myocardial function assessment in patients receiving TAVI.

520 A possible easy way to predict response to cardiac resynchronization therapy: the role of QRS index

Several studies have evaluated the role of QRS duration or QRS narrowing as predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non-responders. However, their results have been conflicting. The aim of our study was to determine the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. We included 115 patients in whom a CRT device was implanted in accordance with current guidelines. Baseline clinical variables, echocardiographic parameters, and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration—QRS duration during CRT)/pre implant QRS duration × 100] were measured. After 6 months, a significant improvement in all echocardiographic parameters was observed. In 103 (90%) patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = +0.19; 95% CI: 0.006–0.35, P = 0.049). The cut-off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity = 65.5%, specificity = 75%, area under the curve = 0.737, P = 0.001). An improvement in their HF clinical composite score at 12 months was found in 23 patients (21%). Considering the improvement in NYHA class, of the 73 patients with QI > 12.25%, 34 (46.5%) had a reduced NYHA class at 12 months post implantation. A statistically significant difference was found between patients with a QI < 12.25%, and those with a QI > 12.25%, in terms of NYHA class worsening (P 0.04). Also a statistically significant difference was found between the mean of the QI of patients who died from cardiovascular causes and patients who died of other causes. We have also investigated the possible sex differences related to QI; women with QI > 12.25% had a statistically significant greater improvement in LVEF at follow-up than men with QI > 12.25% (P 0.03). Patients with a larger decrease in QRSd after CRT initiation showed greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy-to-measure variable that could be used or evaluated to predict CRT response.

254 Impact of sacubitril/valsartan on implantable defibrillator eligibility in heart failure: a real-world experience

Aims Current guidelines recommend an implantable cardiac defibrillator (ICD) in patients with symptomatic heart failure and reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) ≤35%] despite ≥3 months of optimal medical therapy. Recent observations demonstrated that sacubitril/valsartan induces beneficial reverse cardiac remodelling in eligible HFrEF patients. Given the pivotal role of LVEF in the selection of ICD candidates, we sought to assess the impact of sacubitril/valsartan on ICD eligibility and its predictors in HFrEF patients. Methods and results We retrospectively evaluated 48 chronic HFrEF patients receiving sacubitril/valsartan and previously implanted with an ICD in primary prevention. We assumed that ICD was no longer necessary if LVEF improved >35% (or > 30% in asymptomatics) at follow-up. Over a median follow-up of 11 months, sacubitril/valsartan induced a significant drop in LV end-systolic volume (−16.7 ml/m2, P = 0.023) and diameter (−6.8 mm, P = 0.022), resulting in a significant increase in LVEF (+3.9%, P < 0.001). As a consequence, 40% of previously implanted patients resulted no more eligible for ICD at follow-up. NYHA class improved in the 50% of population. A dose-dependent effect was noted, with higher doses associated to more reverse remodelling. Among patients deemed no more eligible for ICD, lower NYHA class [odds ratio (OR): 3.73 (95% CI: 1.05–13.24), P = 0.041], better LVEF [OR: 1.23 (95% CI: 1.01–1.48), P = 0.032], and the treatment with the intermediate or high dose of sacubitril/valsartan [OR: 5.60 (1.15–27.1), P = 0.032] were the most important predictors of status change. Conclusions In symptomatic HFrEF patients, sacubitril/valsartan induced beneficial cardiac reverse remodelling and improved NYHA class. These effects resulted in a significant reduction of patients deemed eligible for ICD in primary prevention.

Use of Cardiac Contractility Modulation in an Older Patient with Non-Ischemic Dilated Cardiomyopathy: A Case Report

Cardiac contractility modulation (CCM) is a novel device-based therapy used in patients with HFrEF. CCM therapy is associated with an improvement in exercise tolerance, increased quality of life, reduced HF hospitalizations, and reverse remodelling of the left ventricle in patients with HFrEF. In this case, we report the clinical benefit of CCM in an older patient with advanced HFrEF due to ischemic dilated cardiomyopathy with frequent heart failure-related hospitalizations and poor quality of life despite optimal medical therapy.

Obesity and Atrial Fibrillation: Epidemiology, Pathogenesis and Effect of Weight Loss

The obesity epidemic continues its relentless advance and is paralleled by an increase in the incidence of AF. Several epidemiological studies have highlighted obesity as an independent risk factor for the development of AF. This relationship is likely multifactorial through a number of interacting mechanisms. Weight loss through lifestyle changes or surgery has been associated with reverse remodelling of the atrial substrate and subsequent reduction in AF, making it an essential pillar in the management of AF in obese patients. In this review, the epidemiological data that support the obesity–AF relationship, the current insights into the underlying pathophysiological mechanism, the impact of weight loss on reverse remodelling and AF reduction, and the strategies to achieve weight loss in patients with AF are discussed.

Cardiac Reverse Remodelling by 2D and 3D Echocardiography in Heart Failure Patients Treated with Sacubitril/Valsartan

In terms of sacubitril/valsartan (S/V)-induced changes in heart failure with reduced ejection fraction (HFrEF) via three-dimensional (3D) transthoracic echocardiography (TTE) and S/V effects based on HF aetiology, data are lacking. We prospectively enrolled 51 HFrEF patients (24 ischaemic, 27 non-ischaemic). At baseline and at 6-month follow-up (6MFU) after S/V treatment optimisation, we assessed the N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac remodelling by two-dimensional (2D) and 3DTTE. In non-ischaemic patients, 2D and 3DTTE showed an improvement in left ventricular (LV) size and biventricular function at 6MFU vs. baseline: 3D-LV end-diastolic volume (EDV) 103 ± 30 vs. 125 ± 32 mL/m2 (p < 0.05), 3D-LV ejection fraction (EF) 40 ± 9 vs. 32 ± 5% (p < 0.05), right ventricular (RV) 3D-EF 48.4 ± 6.5 vs. 44.3 ± 7.5% (p < 0.05); only the 3D method detected RV size reduction: 3D-RVEDV 63 ± 27 vs. 71 ± 30 mL/m2 (p < 0.05). In ischaemic patients, only 3DTTE showed biventricular size and LV function improvement: 3D-LVEDV 112 ± 29 vs. 121 ± 27 mL/m2 (p < 0.05), 3D-LVEF 35 ± 6 vs. 32 ± 5% (p < 0.05), 3D-RVEDV 57 ± 11 vs. 63 ± 14 mL/m2 (p < 0.05); RV function did not ameliorate. In both ischaemic and non-ischaemic patients, diastolic function and NT-proBNP significantly improved. In HFrEF patients treated with S/V, 3DTTE helps to ascertain subtle changes in heart chambers’ size and function, which have a major impact on HFrEF prognosis. S/V has significantly different effects on LV function in non-ischaemic vs. ischaemic patients.