Heart Failure And Reduced Left Ventricular Ejection Fraction Research Articles

Impact of non-typical LBBB on CRT response

Abstract Introduction Cardiac resynchronization therapy (CRT) benefits have been established in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) who have a broad QRS and remain symptomatic despite optimized medical therapy. Responders typically are female, with LBBB and broader QRS. It remains uncertain to what extent do patients with non-LBBB QRS complex morphology respond to CRT and also if there are differences among various types of intraventricular conduction delays. Purpose To evaluate the impact of non-typical left bundle branch block (LBBB) on reverser remodeling and clinical events. Methods Single center, observational, retrospective study including patients (pts) who implanted CRT in the context of HFrEF, from 2015 to 2020. Evaluation of QRS morphology analysis was conducted. CRT response was defined by a reduction of LVESV≥15% or an increase in LVEF≥10%. Predictors of CRT response were evaluated with Chi-square and Mann- Whitney analysis. Impact on reverse remodeling and clinical outcomes was performed with Kaplan-Meyer analysis. Results A total of 361 pts were included for analysis, of which 184 had non-typical LBBB. Pts had a mean age of 71±9years old, the majority of pts were female (61%), and almost half were ischemic (47.8%). EGC evaluation prior to CRT implantation, revealed an atypical LBBB in 83 (45.1%) pts, typical RBBB in 23 (12.5%) pts, atypical RBBB 94.(9%) pts and nonspecific intraventricular conduction delay in 69 (37.5%) pts. During a mean time of follow-up of 2.9 ±2.4years, 33 pts (18%) had hospitalizations due to HF and 68 (37%) died. In this cohort, 78 pts (42.4%) were deemed as responders, who presented a better clinical outcome when compared to non-responders (p < 0.001, HR 2.629 [95% CI 1.635-4.225]. There was no difference among the four types of intraventricular conduction analyzed in respect to degree of CRT response – figure 1. Regarding clinical events during follow-up, there was once again no significant difference among the different patterns of non-typical LBBB– figure 2. In this subset population we found no independent predictors of CRT response, although non-responders were significantly older than responders (72±8 vs 69±10 years-old (p=0.016). Conclusion Although pts with non-typical LBBB morphology display a lower therapy response to CRT than reported for LBBB pts, the rate of response is not negligible and represents a protective factor for clinical outcomes. Different types of intraventricular conduction delay present no difference regarding long- term prognosis or reverse remodeling.Survival according to CRT response

Differential effects of heart failure with reduced ejection fraction on locomotor and respiratory muscles

Abstract Background Muscle weakness impairs quality-of-life, exercise capacity, and survival in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). However, the effects on systemic concentrations and local expression of inflammatory cytokines and myokines as well as metabolic markers might differ between locomotor and respiratory muscles. Purpose We prospectively evaluated clinical, functional, and molecular alterations of the diaphragm and the M. vastus lateralis (MVL) from HFrEF patients receiving a left ventricular assist device compared to patients without heart failure undergoing elective coronary bypass grafting (control). Methods Participants (Controls=21, HFrEF=18) underwent cardiopulmonary exercise and respiratory and leg muscle testing. Serum concentrations and local expression of inflammatory cytokines and myokines as well as key enzymes of metabolic pathways were examined in biopsies of the diaphragm and MVL. Results Exercise capacity, respiratory muscle function and endurance force of locomotor muscles were significantly reduced in HFrEF compared with controls (all p<0.05). The serum concentration of Il-6, Il-1beta and TNF-alpha were significantly higher or solely detectable in HFrEF compared with controls. Local mRNA expression of Il-6 was not different in MVL but 2.2-fold higher in the diaphragm of HFrEF compared with controls (p=0.013). In contrast, mRNA expression of Il-6 receptor was significantly reduced by 38% (p=0.004) in MVL of HFrEF compared with controls but comparable in the diaphragm. Serum concentrations of FGF-21 and Musclin were significantly higher in HFrEF compared with controls (all p<0.05). Local mRNA expression of FGF-21 was significantly lower in both MVL and diaphragm of HFrEF compared with controls. FGF-21 receptor 1 mRNA expression was reduced by 18% in the MVL of HFrEF (p=0.02), whereas co-receptor klotho was comparable to controls. In the diaphragm, FGF-21 receptor 1 mRNA expression was comparable between HFrEF and controls, but the co-receptor klotho had a 5-fold higher mRNA expression in HFrEF (p=0.002). We examined the activity of key enzymes of glucose, lipid and ketone metabolism as well as key enzymes of the Krebs cycle. The main differences were found for ß-hydroxyacyl-CoA Dehydrogenase in the diaphragm with a 1.6-fold higher activity in HFrEF compared with controls (p=0.01) and for succinyl-CoA: 3-ketoacid-coenzyme A transferase in the MVL with a 2-fold higher activity in HFrEF compared with controls (p<0.01) indicating a main utilization of lipids in the diaphragm and of ketones in the MVL for energy supply. Conclusions HFrEF induced divergent effects on inflammatory markers, myokine expression and metabolic parameters in locomotor and respiratory muscles in HFrEF patients compared with controls. This indicates that different molecular alterations contribute to locomotor/respiratory muscle dysfunction and reduced whole-body exercise capacity.

P71 SGLT2I IN THE REAL WORLD: DATA FROM THE PONTE (BRIDGE) HF PROJECT (PDTA FOR INTEGRATED TERRITORY HOSPITAL FOLLOW–UP OF PATIENTS WITH HEART FAILURE)

Abstract Background The DAPA–HF and the EMPEROR reduced trials showed that sodium–glucose cotransporter type 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin, on best medical therapy, resulted in a reduced incidence of the combined primary outcome cardiovascular death and worsening heart failure (–26%) and a preventive effect on renal function decline. Based on this evidence, the 2021 ESC guidelines have included SGLT2i in class I recommendations in combination with angiotensin and neprilysin receptor inhibitors (ARNI) or ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB), beta–blockers (BB), and mineral corticoid receptor antagonists (MRA). However, the effect of adding SGLT2i in real–life patients is just partly known. The aim of the study was therefore to evaluate the impact of SGLT2i in a real world population of patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Methods 220 consecutive patients with HFrEF, treated with SGLT2i and with 6 months of follow–up already enrolled in the PONTE (BRIDGE) HF project (PDTA FOR THE INTEGRATED FOLLOW–UP IN THE HOSPITAL TERRITORY OF THE PATIENT WITH HEART FAILURE), a care model implemented in Puglia region (Italy) based on hospital–territory integration aimed at the optimized management of patient with HF after hospitalization, were considered for the study. Demographic, clinical, laboratory and instrumental characteristics and changes in NYHA class, creatinine, NT proBNP, loop diuretic dose, LVEF after initiation of therapy with SGLT2i were evaluated. Results The 220 enrolled patients (mean age of 62 years, 72% hypertensive, 38% diabetic, 67% with ischemic heart disease, 50% with ICD/CRT, 44% with atrial fibrillation, 5.6% in NYHA class I, 61% class II, 33% class III, mean LVEF 30±11%) were in treatment with BB in 93% of cases, with MRA in 94%, with ACE/ARB in 24% and with ARNI in 80%. At 6–month follow–up of, a reduction of patients in NYHA class III from 33 to 20%, an increase in patients in NYHA class II from 61 to 70%, and in NYHA class I from 5.6 to 10% were observed; the LVEF (30 vs 37.2%) and creatinine values (1.3 vs 1.5) increased significantly, while loop diuretic doses decreased (35 vs 97.5). Conclusions Data from patients treated with SGLT2i from real world seem to confirm the efficacy of this class of drugs already in a short term follow–up, with a positive effect on NYHA class, LVEF, and renal function.

Aiming at harmony. Comparing and contrasting International HFrEF Guidelines.

Large randomized controlled trials (RCTs) have led to major changes in the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) and these advances are included in the recent European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines issued in 2021 and 2022, respectively. According to both guidelines, treatment of patients with HFrEF is based on the administration of four classes of drugs that reduce the primary endpoint of cardiovascular death and HF hospitalizations in RCTs: angiotensin-converting enzyme or angiotensin receptor neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors. Specific sequences of treatment are not recommended but emphasis is given to reaching treatment with all four drugs as early as possible. Further treatments are considered in selected patients including ivabradine, hydralazine nitrates, digoxin, and the new agent vericiguat. Specific treatments, mostly new, for cardiovascular and non-cardiovascular comorbidities are also given. The aim of this article is to compare the two recent guidelines issued by the ESC and ACC/AHA/HFSA and show the few differences and the many consistent recommendations, now more numerous given the evidence available for many new treatments.

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

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

Quality of life in patients with heart failure and improved ejection fraction: one-year changes and prognosis.

The criteria for patients with heart failure (HF) and improved ejection fraction (HFimpEF) are a baseline left ventricular ejection fraction (LVEF) ≤40%, a ≥10-point increase from baseline LVEF, and a second LVEF measurement >40%. We aimed to (i) assess patients with HF and reduced LVEF (HFrEF) at baseline and compare quality of life (QoL) changes between those that fulfilled and those that did not fulfil the HFimpEF criteria 1year later and (ii) assess the prognostic role of QoL in patients with HFimpEF. We reviewed data from a prospective registry of real-world outpatients with HF that were assessed for LVEF and QoL at a first visit to the HF clinic and 1year later. QoL was evaluated with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The primary prognostic endpoint was the composite of all-cause death or HF hospitalization. Baseline and 1-year LVEF and MLWFQ scores were available for 1040 patients with an initial LVEF ≤40% (mean age, 65.2±11.7years; 75.9% men). The main aetiology was ischaemic heart disease (52.9%), and patients were mostly in New York heart Association Classes II (71.1%) and III (21.6%). At baseline, the mean LVEF was 28.5%±7.3, and the mean MLWHFQ score was 30.2±19.5. After 1year, the mean LVEF increased to 38.0%±12.2, and the MLWHFQ scores improved to 17.4±16.0. In 361 patients that fulfilled the HFimpEF criteria (34.7%), significant improvements were observed in both LVEF (from 28.7%±6.6 to 50.9%±7.6, P<0.001) and QoL (from 32.9±20.6 to 16.9±16.0, P<0.001). Patients that did not fulfil the HFimpEF criteria also showed significant improvements in LVEF (from 28.4%±7.6 to 31.1%±7.9, P<0.001) and QoL (from 28.7±18.8 to 17.6±15.9, P<0.001). However, the QoL improvement was significantly higher in the HFimpEF group (-16.0±23.8 vs. -11.1±20.3, P=0.001), despite the worse mean baseline MLWHFQ score, compared with the non-HFimpEF group (P=0.001). The 1-year QoL was similar between groups (P=0.50). The 1-year MLWHFQ score was independently associated with outcomes; the hazard ratio for the composite endpoint was 1.02 (95% CI: 1.01-1.03, P=0.006). In contrast, the QoL improvement (with a cut-off ≥5 points) was not independently associated with the composite outcome. Patients with HFrEF showed improved QoL after 1year, regardless of whether they met the HFimpEF criteria. The similar 1-year QoL perception between groups suggested that factors other than LVEF influenced QoL perception. The 1-year QoL was superior to the QoL change from baseline for predicting prognosis in patients with HFimpEF.

Natriuretic Peptide-guided Therapy for Heart Failure.

Heart failure (HF) is a complex syndrome with high mortality and hospitalization rates. Conventional care in patients with HF is usually based on clinical history and physical examination. Natriuretic peptides (NPs), B-type NP (BNP) and N-terminal proBNP, are the gold-standard biomarkers in HF. They are recommended for diagnosing HF, when the physician is uncertain of the diagnosis, and for estimating the prognosis. NPs also guide therapy in HF, as serial NP measurements inform medication adjustments to achieve targets independently of symptoms. In this regard, the data are conflicting. In patients with HF and reduced left ventricular ejection fraction (HFrEF) there is a suggestion that NP-guided therapy is helpful. The studies STARS-BNP and PROTECT demonstrated a reduction in cardiac events with NP-guided therapy. Additionally, mortality in patients aged <75 years reduced in the BATTLESCARRED and TIME-CHF studies, and in a meta-analysis. On the contrary, no differences were observed in the studies PRIMA and GUIDE-IT. In HF with preserved ejection fraction (HFpEF) and in the acute setting, no differences were detected with NP-guided therapy compared with conventional care. In patients at risk of developing HF, NP can be useful to guide therapy and prevent HF. In summary, NP-guided therapy seems to be useful in patients with HFrEF, especially in those aged <75 years, but has no use in HFpEF or in acute HF.

Dapagliflozin — a key pawn on the new guidelines chessboard

Treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) aims to reduce mortality, prevent rehospitalizations due to heart failure (HF) exacerbation, and improve the clinical status, functional capacity, and quality of life. All these goals were achieved in the DAPA-HF trial. In this trial, the reduction in the primary outcome, defined as a composite of worsening of HF or cardiovascular death, was achieved in patients receiving dapagliflozin [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65–0.85; p &lt; 0.001) as compared with placebo. In addition, the beneficial effect of dapagliflozin on the primary outcome was generally consistent across prespecified subgroups regardless of baseline treatment, diagnosis of diabetes, or left ventricular ejection fraction (LVEF). Data from multiple countries was obtained in the CVD-REAL study. The use of different sodium-glucose co-transporter 2 (SGLT2) inhibitors, versus other glucose-lowering drugs, was associated with lower rates of hospitalization for HF (HR 0.61; 95% CI 0.51–0.73; p &lt; 0.001) and death (HR 0.49; 95% CI 0.41–0.57; p &lt; 0.001). These findings were confirmed in the CVD-REAL-2 study. The exceptional clinical benefits of SGLT2 inhibitors applied on top of the previously guideline recommended treatment in patients with chronic HFrEF led to fundamental changes in the recommended treatment strategy proposed in the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic HF. To conclude, the new treatment algorithm for HFrEF is based on the findings of many groundbreaking trials. However, it is the results of trials with SGLT2 inhibitors, applied in patients with HFrEF on top of the optimal treatment including an implantable cardioverter-defibrillator and/or cardiac resynchronization therapy, that have fundamentally changed the strategy of treatment.

Trend of perceived quality of life and functional capacity in outpatients with chronic heart failure and in treatment with sacubitril/valsartan: a real-life experience.

Despite the use of optimal medical therapy, heart failure and reduced left ventricular ejection fraction (HFrEF) remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with HFrEF. The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. We enrolled 37 patients (63±10 years old, 76% men) who underwent a total of one-year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular, NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NT-ProBNP, BNP and NYHA class. However, analyzing the ∆% of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction

ABSTRACT Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death. Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA). Results: A total of 61 patients died during the median follow-up of 7.0 [5.2–8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08–1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98–1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92–3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07–1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29–2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12–3.77], p = 0.020) were associated with a higher risk for overall mortality. Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

Application of survival classification and regression tree analysis for identification of subgroups of risk in patients with heart failure and reduced left ventricular ejection fraction.

The aim of this study was to identify by classification and regression tree (CART) analysis groups of patients with different survival patterns in a population of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) by using standard methods of heart function assessment, as well as well as utilizing non-traditional approaches for determining hydration and nutritional status in HF patients-lung ultrasonography (LUS) and bioimpedance spectroscopy (BIS) analysis. Eligible patients with a left ventricular ejection fraction (LVEF) below 45% were identified via the daily echocardiography assessments. LUS was performed with patients in the supine position, for a total of 28 sites per complete examination. The hydration state and the body composition were assessed using a portable whole-body BIS device. Our study included 151 patients (69.2% males) with a mean age of 67.1years. During the follow-up 53 (35.1%) patients died. Using the CART algorithm, we identified five groups based on serum sodium, the severity of NYHA class, serum urea and systolic blood pressure. When comparing the two models, the model derived from the CART analysis showed better predictive power than the conventional Cox model (c-index 0.790, 95% CI 0.723-0.857 vs. 0.736, 95%CI 0.664-0.807, p < 0.05). The application of CART analysis allowed us to identify different groups of risk for all-cause mortality in patients with HFrEF. The use of this type of modelling showed better prediction capabilities over that of using more conventional statistical approach.ClinicalTrials.gov Identifier: NCT02764073.

Prognostic significance of cardiac 123I-MIBG SPECT imaging in patients with acute decompensated heart failure with preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with heart failure (HF). Most of the literature on the use of 123I-MIBG imaging is based on planar images in patients with chronic HF and reduced left ventricular ejection fraction (HFrEF), because It is technically challenging to conduct precise 123I-MIBG SPECT analysis in globally denervated heart, which is frequently observed in HFrEF patients. There was no information available on cardiac sympathetic nerve dysfunction evaluated by cardiac MIBG SPECT imaging in acute decompensated HF (ADHF) patients with preserved left ventricular ejection fraction (HFpEF). Purpose We aimed to clarify the prognostic significance of 123I-MIBG SPECT myocardial imaging in ADHF patients with HFpEF. Methods We enrolled 183 patients who were admitted for ADHF with HFpEF, discharged with survival. All patients underwent cardiac MIBG imaging at the timing of discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). We studied 156 patients after excluding 27 patients whose MIBG SPECT reconstruction was difficult due to too low MIBG uptake or extracardiac accumulation interference. SPECT analysis on the delayed image was conducted by using CardioBull, a fully automated software for the quantification of I-123 MIBG SPECT. All of 17 regional tracer uptake were compared with normal control database. A scoring algorithm for the evaluation of low uptake employs a 5-point scoring system as 0–4 for normal, mildly abnormal, moderately abnormal, severe abnormal, and perfusion defect, respectively. The summed severity (SSS) scores were obtained by summing the score for all segments. SSS could range from 0 to 68. The endpoint of this study is cardiac events defined as the composite of unplanned heart failure hospitalization and cardiac death. Results During a mean follow up period of 2.4±1.6 years, 60 patients reached cardiac events. SSS was significantly high in patients with than without cardiac events (20 [10–27] vs 7 [4–16], p&amp;lt;0.0001). SSS (p&amp;lt;0.0001) was significantly associated with cardiac events after multivariable Cox adjustment of age, sex, creatinine and log-transformed BNP level, although late H/M showed the significant association with the endpoint at the univariate Cox analysis. Kaplan-Meier analysis showed that patients with high SSS (&amp;gt;10, defined by median) had significantly greater risk of cardiac event (56% vs 21%, Hazard ratio: 3.56 (2.00–6.33, p&amp;lt;0.0001). ROC curve analysis showed that area under the curve (AUC) of SSS was 0.746 [95% CI:0.670, 0.812], which was significantly higher than that of late H/M (0.618 [95% CI:0.537, 0.695]) (p=0.0159). Conclusion Cardiac MIBG SPECT imaging was useful for risk stratification in ADHF patients with HFpEF. Funding Acknowledgement Type of funding source: None

Non-invasive telemonitoring improves outcomes in heart failure with reduced ejection fraction: a study in high-risk patients.

AimsNon‐invasive telemonitoring (TM) in patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF) may be useful in the early diagnosis of HF decompensation, allowing therapeutic optimization and avoiding re‐hospitalization. We describe a TM programme in this population and evaluate its effectiveness during a 12 month period.Methods and resultsWe conducted a single‐centre study of patients discharged from hospital after decompensated HF, allocated into three groups: prospective TM programme, prospective HF protocol follow‐up programme (PFP) with no TM facilities, and retrospective propensity‐matched usual care (UC). TM effectiveness was assessed by all‐cause hospitalizations and mortality; HF‐related hospitalization (HFH), days lost to unplanned hospital admissions/death, functional capacity and quality of life (New York Heart Association, Kansas City Cardiomyopathy Questionnaire, 6 min walk test, and plasma N‐terminal pro‐brain natriuretic peptide) were also evaluated. A total of 125 patients were included [65.9 ± 11.9 years, 32% female, left ventricular ejection fraction 27% (21–32)]. TM was similar to PFP regarding effectiveness; TM reduced all‐cause hospitalization and mortality (HR 0.27; 95% CI 0.11–0.71; P < 0.01) and HFH (HR 0.29; 95% CI 0.10–0.89; P < 0.05) as compared with UC. TM reduced the average number of days lost due to unplanned hospital admissions or all‐cause death as compared with PFP (5.6 vs. 12.4 days, P < 0.05) and UC (5.6 vs. 48.8 days, P < 0.01). Impact on quality of life was similar between TM and PFP (P = 0.36).ConclusionsIn patients with HFrEF and recent HF hospitalization, non‐invasive TM reduced 12 month all‐cause hospitalization/mortality and HFH as compared with usual care. TM also reduced the number of days lost due to unplanned hospital admission/death as compared with either an optimized protocol‐based follow‐up programme or usual care.

Response to ECG, August 2020

A prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3–6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR.Consecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up.One hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81.Pharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation.

The role of sacubitril/valsartan in the treatment of chronic heart failure with reduced ejection fraction in hypertensive patients with comorbidities: From clinical trials to real-world settings

BackgroundSacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. MethodsIn this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ± 8.2 years, 75.0 % male), with HFrEF (29.8 ± 4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. ResultsNYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p < 0.05 for all). A significant improvement in LVEF and eGFR levels was found in the ARNI arm compared to controls (42.4 vs. 34.2 %, 73.8 vs. 61.2 mL/min, respectively; p < 0.001 for all). NT-proBNP, clinic systolic and diastolic BP, blood glucose, HbA1c and UA values were reduced in both treatment arms, but they were lower in the ARNI arm compared controls (3107 vs. 4552 pg/mL, 112.2 vs. 120.4 and 68.8 vs. 75.6 mmHg, 108.4 vs. 112.6 mg/dL, 5.4 vs. 5.9 % and 5.9 vs. 6.4 mg/dL, respectively, p < 0.05). Mortality and re-hospitalization for HF was lower in the ARNI arm than controls (20.1 vs. 33.6 % and 27.7 vs. 46.3 % respectively; p < 0.05 for all). Gender differences were not found in either arm. No patients refused to continue the study, and no side effects to the ARNI treatment were observed. ConclusionsIn elderly patients with HFrEF and comorbidities, ARNI treatment seems effective and safe. The improvement in LVEF and cardiac remodeling, BP, eGFR, serum glucose, UA and HbA1c could be the mechanisms by which ARNIs play their beneficial role on clinical outcomes. However, these results need to be confirmed in studies involving a greater number of subjects, and with a longer follow-up.

Indications of Cardiac Resynchronization in Non-Left Bundle Branch Block: Clinical Review of Available Evidence.

Cardiac resynchronization therapy (CRT) benefits have been firmly established in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), who remain in New York Heart Association (NYHA) functional classes II and III, despite optimal medical therapy, and have a wide QRS complex. An important and consistent finding in published systematic reviews and in subgroup analyses is that the benefits of CRT are maximum for patients with a broader QRS durations, typically described as QRS duration > 150 ms, and for patients with a typical left bundle branch block (LBBB) QRS morphology. It remains uncertain whether patients with non-LBBB QRS complex morphology clearly benefit from CRT or only modestly respond.

P6251Prognostic value of ACEi/ARBS in elderly patients with heart failure with reduced ejection fraction with and without chronic kidney disease

Abstract Introduction Angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers therapy (ACEI/ARB) have shown to reduce mortality in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). However, there is lack of information about the benefit of these drugs in patients with chronic kidney disease (CKD), and even less in elderly patients. Our aim is to compare the prognostic impact of ACE/ARB if CKD is present or not Methods From January 2008 to July 2014, we consecutively enlisted 802 patients aged &gt;75 years that had ejection fraction ≤35%. Clinical, echocardiographic and ECG data were taken from hospital records. Follow-up was made via telephone and hospital records as well. We analyzed the relationship between treatment with ACEi/ARBs (with different doses) and occurrence of mortality or MACE (major adverse cardiovascular events: composite of death from any cause or hospitalization for heart failure). Results From the total population 410 (51%) patients that had not CKD (glomerular filtration rate (GFR) &gt;60ml/min/1,73m2) and 390 (49%) patients had CKD (with GFR ≤60ml/min/1,73m2). We analyze the population according the presence or not of CKD. Both groups had similar characteristics except the age: 81.5±4.5 years vs. 82.6±4.1 (p&lt;0.05) and the percentage of use of ACEi/ARB 78.8% of the total vs 66.9% of the total (p&lt;0.05). The mean ejection fraction was 27.9±6.5% vs 28.12±6.5% (p&gt;0.05). The mean follow up was 33±22 vs 32±23 months (p&gt;0.05). In patients with no CKD 170 (42%) patients died and 239 (58%) patients had a MACE. In the CKD group 211 (54.1%)patients died and 257 (65.9%)patients had a major cardiovascular event. In the univariate analysis in both groups the use of ACEi/ARB reduced the mortality and the MACE. After a multivariate analysis ACEi/ARB appear to be beneficial in the CKD group (OR 0.71 [0.50–0.98]) but not in no CKD group Conclusions According to our data, treatment with ACEI/ARB in elderly patients HFrEF and CKD should be encouraged even more than in those without CKD.

Effect of comprehensive initial training on the variability of left ventricular measures using fast-SENC cardiac magnetic resonance imaging

Cardiac magnetic resonance (CMR) is becoming the imaging modality of choice in multicenter studies where highly reproducible measurements are necessary. The purpose of this study was to assess the effect of comprehensive initial training on reproducibility of quantitative left ventricular (LV) parameters estimated using strain-encoded (SENC) imaging. Thirty participants (10 patients with heart failure (HF) and preserved LV ejection fraction (HFpEF), 10 patients with HF and reduced LV ejection fraction (HFrEF) and 10 healthy volunteers) were examined using fast-SENC imaging. Four observers with different experience in non-invasive cardiac imaging completed comprehensive initial training course and were invited to perform CMR data analysis. To assess agreement between observers, LV volumes, mass, ejection fraction (LVEF), global longitudinal strain (GLS) and global circumferential strain (GCS) were estimated using dedicated software (MyoStrain, USA). To test intraobserver agreement data analysis was repeated after 4 weeks. SENC imaging and analysis were fast and were completed in less than 5 minutes. LV end-diastolic volume index (LVEDVi), LVEF and strain were significantly lower in HFpEF patients than in healthy volunteers (p = 0.019 for LVEDVi; p = 0.023 for LVEF; p = 0.004 for GLS and p < 0.001 for GCS). All LV functional parameters were further reduced in HFrEF. Excellent interobserver agreement was found for all LV parameters independently of the level of experience. The reproducibility of LV mass was lower, especially at the intraobserver level (ICC 0.91; 95% CI 0.74–0.96). LV volumetric and functional parameters derived using fast-SENC imaging, are highly reproducible. The appropriate initial training is relevant and allows to achieve highest concordance in fast-SENC measurements.

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS/ANGIOTENSIN RECEPTOR BLOCKERS IN ELDERLY PATIENTS WITH LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND ADVANCED CHRONIC KIDNEY DISEASE: DANGER OR BENEFIT?

Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy (ACEI/ARB) have shown to reduce mortality in patients with heart failure and reducedleft ventricular ejection fraction (HFrEF). However, there is lack of information about the benefit of these drugs in patients with HFrEF

A risk score to predict the absence of left ventricular reverse remodeling: Implications for the timing of ICD implantation in primary prevention

BackgroundA prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3–6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR. MethodsConsecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up. ResultsOne hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81. ConclusionsPharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation.