HFrEF Patients Research Articles

Regurgitant volume to left ventricular end-diastolic volume ratio: the quest to identify Disproportionate MR is not over

Abstract Background Quantification of secondary mitral valve regurgitation (SMR) remains challenging. Proportionate and Disproportionate SMR provides a conceptual framework that relates the degree of SMR to left ventricular dilatation and dysfunction. In line with this concept, regurgitant volume to LV end-diastolic volume ratio (Rvol/LVEDV) was recently proposed as a possible strategy to identify patients with Disproportionate SMR. The aim of this study was to validate this approach in a Portuguese cohort. Methods In a single center cohort of patients with heart failure and reduced left ventricular ejection fraction (HFrEF <50%) under optimal guideline-directed medical therapy (GDMT), we retrospectively identified those with at least moderate SMR. According to the published literature, we divided the study population into 2 risk groups: those with a Rvol/LVEDV ratio ≥20% (greater MR/smaller LVEDV) and those with a ratio <20% (smaller MR/ larger EDV). Cox regression and Kaplan-Meier survival analysis were used to assess the association between Rvol/LVEDV ratio and all-cause mortality. Results A total of 154 patients (mean age 69±12 years; 81% male) were included. Mean LVEF was 31±8% and median LVEDV was 193 mL (IQR: 155 to 236 mL). There were 74 patients (48.1%) with a Rvol/LVEDV ratio <20% and 80 patients (51.9%) Rvol/LVEDV ratio ≥20%. Regarding GDMT, 141 (91.6%) received beta-blockers, 139 (90.3%) angiotensin converting–enzyme inhibitors/angiotensin receptor blockers and 77 (50.0%) were under mineralocorticoid therapy. Also, there were patients 49 (31.8%) under cardiac resynchronization therapy and 40 patients (26.0%) had an implantable cardioverter defibrillator. During a median follow-up of 2.1 years (IQR 0.7 to 3.8 years), 92 (59.7%) patients died. Cox regression and survival analysis showed no mortality difference between patients with a Rvol/LVEDV ratio <20% and those with a ratio ≥20% (HR: 1.04; 95% CI 0.69–1.57; P=0.854; Log-rank P=0.967) – see also figure. Conclusion In a Portuguese cohort of HFrEF patients under optimized GDMT and with at least moderate SMR, the Rvol/LVEDV ratio was not associated with an increased risk of all-cause mortality. As such, the Rvol/LVEDV ratio does not seem to be a reliable surrogate of Disproportionate SMR, possibly because it does not account for the degree of LV dysfunction. Funding Acknowledgement Type of funding sources: None.

BLITZ-HF study: a nationwide initiative to assess and improve guidelines recommendations adherence in cardiology centers managing patients with acute and chronic heart failure

Abstract Background Physicians adherence to heart failure (HF) guidelines is generally sub-optimal with consequent negative prognostic implications. Strategies to improve adherence to guideline recommendations are strongly needed. Aims To assess and improve adherence of Italian cardiology sites to guidelines recommendations on performance indicators in patients with acute (AHF) and chronic heart failure (CHF). Methods BLITZ-HF was a prospective study based on a web based recording system used during two enrollment periods (phase 1 and 3), interspersed by face-to-face macro-regional benchmark analysis and educational meetings (phase 2). Both management (creatinine and echocardiographic evaluations or discharge follow-up planning) and treatment (according to ejection fraction categories, focusing on guidelines directed medical treatments - GDMTs) performance indicators were considered for patients in both settings. Results Overall, 7218 patients with acute and chronic HF were enrolled at 106 sites. During the enrollment phases, 3920 and 3298 patients were included respectively, 84% with CHF and 16% with AHF in phase 1, 74% with CHF and 26% with AHF in phase 3. In Figure 1 we report adherence to management and treatment indicators in the two enrollment phases. Among AHF patients improvement was obtained in two of seven indicators. A significant rise in echocardiographic evaluation was observed, while discharge schedule of a cardiology ambulatory evaluation within four weeks was overall poor (less than 50%) and did not improve in the 3 phase. Overall GDMTs prescription rate in HFrEF was good and we observed a nominal increase in betablockers prescription rate in Phase 3. Among CHF patients with HFpEF and HFmrEF we observed a performance increase in two of three indicators: creatinine end echocardiographic evaluations, while oral anticoagulation in atrial fibrillation remained stably high. Performance measures in CHF HFrEF patients improved in six of nine indicators although significantly only in two. Prescription rate of GDMTs was good already in phase 1 and a significant increase in ACE-I/ARB or ARNI prescription was reported, with a nominal increase in the use of one of these three drugs in combination with MRAs and a BB. Conclusions A structured multifaceted educational intervention can improve adherence to HF guidelines on several indicators in a context of an already elevated level of adherence to guideline recommendations. Extension of this approach to other non-cardiology health professional settings, in which patients with HF are generally managed, should be considered. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was funded by Heart Care Foundation with a partial unrestricted support from Abbott, Daiichi Sankyo, Medtronic, Servier, Vifor.

EFFECT OF MODERN VERSUS STANDARD OF CARE ANTI-FAILURE MEDICATIONS ON LEFT VENTRICULAR FUNCTION IN HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION AS DETECTED BY2D SPECKLE TRACKING ECHOCARDIOGRAPHY

Background: Heart failure (HF) is a major and growing public health problem, as 21 million adults worldwide are living with heart failure and this number is expected to rise due to aging population, increasing prevalence of risk factors and improved post myocardial infarction (MI) survival. Objective: This study was discuss the effect of modern versus standard of care anti failure medications on LV function in heart failure patients with reduced ejection fraction using 2D speckle tracking echocardiography. Patients and methods: The study population includes 100 heart failure patients with reduced ejection fraction 50 on modern anti-failure medications including angiotensin receptor neprilysin inhibitor (ARNI) and 50 controls on standard anti-failure medications including angiotensin I-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARBs). All patients attended the outpatient clinic of the Cardiology Department at Al-Azhar University Hospital (Cairo) from March 2020 to March 2021. Results: There was no significant statistical difference between groups also regard sex distribution there was no significant difference between groups and male were majority in both groups. There was no significant difference between the two studied groups regarding levels of serum creatinine and serum K. Results of comparison of end systolic, end diastolic diameters of left ventricle and diameter of left atrium showed no significant difference between both groups at pre medication assessment but there was a highly significant after medications in both groups (p= 0.00, 0.038 and 0.035 respectively) also in group A there was a significant decrease from pre to post assessment (p=0.003, 0.012 and 0.004 respectively). There was a statistically significant improve in mitral regurgitation after medication in group A than in group B (p=0.00) but was of no significant in pre medication assessment (p=0.48). Conclusion: In HFrEF patients, sacubitril/valsartan significantly improves the mitral regurgitation LV remodeling and with a significant effect on LV diastolic and systolic echo parameters. Accordingly, sacubitril/valsartan could be used at an earlier time in HFrEF patients in order to further limit LV remodeling.

Benefits and adverse effects of sacubitril/valsartan in patients with chronic heart failure: A systematic review and meta-analysis.

This review aims to assess the benefits and adverse effects of sacubitril/valsartan in heart failure, with a focus on important patient outcomes. A systematic review was conducted of double‐blind randomized controlled trials (RCTs) comparing sacubitril/valsartan versus a reference drug, in heart failure patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction, published in French or English. Searches were undertaken of Medline, Cochrane Central, and Embase. The primary outcomes were all‐cause mortality and adverse events. From 2 082 articles analyzed, 5 were included. For all‐cause mortality, the absolute numbers for HFrEF (2 RCTs, 4627 patients) were 16% on sacubitril/valsartan and 18% on enalapril, with a risk ratio (RR) of 0.85 [CI = 0.78, 0.93], and 13% vs 14% in with HFpEF (2 RCTs, 5097 patients), with no statistical difference. Under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the evidence for HFrEF patients was of moderate quality. For HFrEF patients, an increased risk of symptomatic hypotension and angioedema (low quality of evidence) was shown. There was no statistical difference for the risk of hyperkalemia or worsening renal function. There was a protective RR (0.50 [0.34, 0.75]) for worsening renal function for patients with HFpEF, with a high quality of evidence despite similar absolute numbers (1.4% vs. 2.8%). To keep in mind for shared decision‐making, sacubitril/valsartan reduces all‐cause mortality in HFrEF patients but for HFpEF further data are needed. Take into consideration the small number of studies to date to assess the risks.

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Despite concern that a higher risk of side effects might alter the net risk/benefit ratio for neurohormonal therapy, which includes beta-blockers and ACEi/ARB/ARNI in older HFrEF patients, the benefits of neurohormonal therapy do not decrease with increasing age. See the related article by Gilstrap, pages 2811-2820.

Looking for a Tailored Therapy for Heart Failure: Are We Capable of Treating the Patient Instead of the Disease?

After almost a decade of stagnation in clinical research for HF treatment, five large randomized trials recently published have supported the use of four new classes of drugs, namely: angiotensin receptor/neprilysin inhibitor, sodium–glucose co-transporters 2 inhibitors, soluble guanylate cyclase modulators, and myosin activators. Each treatment has proved to be beneficial for both long-term outcomes and quality of life. Beside their clinical relevance, all these novel treatments have a different mechanism of action beyond the usual neuro-hormonal blockage. These different pathways, together with the unquestionable clinical evidence, advocate a re-thinking of HF treatment and of the appropriate drug to integrate with the existing standard therapy, according to different characteristics of HFrEF patients. This study aimed to offer a synthetic overview of the mechanisms of action of the new drugs and to propose a more personalized approach, considering patients’ characteristics and safety profiles. To this end, we have identified seven profiles for patients with chronic heart failure with reduced ejection fraction and two for pre-discharge patients.

Sympathetic activation in heart failure with reduced and mildly reduced ejection fraction: the role of aetiology.

AimWhile sympathetic overactivity in heart failure (HF) with reduced ejection fraction (HFrEF; EF < 40%) is well‐documented, it is ill‐defined in patients with mildly reduced EF (HFmrEF; EF 40–49%). Furthermore, the significance of ischaemic versus non‐ischaemic aetiology in sympathetic activation is also unclear and has yet to be studied in HF. Our goal was to compare muscle sympathetic nerve activity (MSNA) in HFmrEF and HFrEF patients and in healthy subjects, as well as to elucidate the influence of the underlying disease.Methods and resultsTwenty‐three HFrEF (age 58 ± 10 years), 33 HFmrEF patients (age 61 ± 10 years), including 11 subjects with non‐ischaemic cardiomyopathy in each HF groups and 10 healthy controls (age 55 ± 10 years), were studied. MSNA—detected by peroneal microneurography, continuous arterial pressure, and ECG—was recorded. MSNA frequency (burst/min) and incidence (burst/100 cycles) were calculated. Association with the patients' characteristics were assessed, and aetiology‐based comparisons were performed. Burst frequency demonstrated a significant stepwise increase in both HFmrEF (41 ± 11 burst/min) and HFrEF (58 ± 17 burst/min, P < 0.001) patients as compared with controls (27 ± 9; P < 0.001 for both HF groups). Similarly, burst incidences were 66 ± 17, 82 ± 15, and 36 ± 10 burst/100 cycles in HFmrEF, HFrEF patients, and in healthy controls, respectively (P < 0.001 for all). Burst frequencies in HF patients showed significant correlation with NT‐proBNP levels, and significant inverse correlations with the subjects' mean RR intervals, stroke volumes, pulse pressures, and EF.ConclusionsMuscle sympathetic nerve activity parameters indicated significant sympathetic activation in both HFmrEF and HFrEF patients as compared with healthy controls with no difference in relation to ischaemic versus non‐ischaemic aetiology.

Impact of epicardial adipose tissue on cardiovascular haemodynamics, metabolic profile, and prognosis in heart failure.

We evaluated the impact of echocardiographic epicardial adipose tissue (EAT) on cardiovascular haemodynamics, metabolic profile and prognosis in heart failure (HF) using combined cardiopulmonary-echocardiography exercise stress. We analysed EAT thickness of HF patients with reduced (HFrEF, n=205) and preserved (HFpEF, n=188) ejection fraction, including 44 controls. HFpEF patients displayed the highest EAT, while HFrEF patients had lower values than controls. EAT showed an inverse correlation with natriuretic peptides, troponin T and C-reactive protein in HFrEF, while having a direct association with troponin T and C-reactive protein in HFpEF. EAT was independently associated with peak oxygen consumption (VO2 ) and peripheral extraction (AVO2 diff), regardless of body mass index. EAT was inversely correlated with peak VO2 and AVO2 diff in HFpEF, while a direct association was observed in HFrEF, where lower EAT values were associated with worse left ventricular systolic dysfunction. In HFpEF, increased EAT was related to right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) uncoupling. After 21 months of follow-up, 146 HF hospitalizations and 34 cardiovascular deaths were recorded in the HF population. Cox multivariable analysis supported an independent differential role of EAT in HF cohorts (interaction P=0.01): higher risk of adverse events for increasing EAT in HFpEF [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.37] and for decreasing EAT in HFrEF (HR 0.75, 95% CI 0.54-0.91). In HFpEF, EAT accumulation is associated with worse haemodynamic and metabolic profile, also affecting survival. Conversely, lower EAT values imply higher left ventricular dysfunction, global functional impairment and adverse prognosis in HFrEF.

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

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 remodeling 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. 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% if 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 50% of the population. A dose-dependent effect was noted, with higher doses associated to more reverse remodeling. 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. In symptomatic HFrEF patients, sacubitril/valsartan induced beneficial cardiac reverse remodeling and improved NYHA class. These effects resulted in a significant reduction of patients deemed eligible for ICD in primary prevention.

The Use of β-Blockers in Heart Failure with Reduced Ejection Fraction.

Treatment with β-blockers is the main strategy for managing patients with heart failure and reduced ejection fraction because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with consequent prognostic and symptomatic benefits. However, to date, they are underused, mainly because of the misconception that hypotension and bradycardia may worsen the haemodynamic status of patients with HFrEF and because of the presence of comorbidities falsely believed to be absolute contraindications to their use. To promote proper use of β-blockers in this article, we review the clinical pharmacology of β-blockers, the evidence of the beneficial effects of these drugs in heart failure with reduced ejection fraction, and the current guidelines for their use in clinical practice and in the presence of comorbidities (e.g., pulmonary disease, diabetes, atrial fibrillation, peripheral arterial disease, etc.). It is hoped that the practical approach discussed in this review will allow for a proper diffusion of knowledge about the correct use of β-blockers and the drug-disease interactions to achieve their increased use and titration, as well as for the selection of a specific agent with a view to a properly tailored approach for HFrEF patients.

Prognostic value of right ventricular echocardiographic measures in patients with heart failure with reduced ejection fraction.

Right ventricular (RV) dysfunction is associated with poor outcome in patients with heart failure. In order to better predict mortality in this patient group we wanted to compare the prognostic value of conventional and advanced RV echocardiographic measures. Echocardiographic examinations were retrieved from 701 patients. End point was all-cause mortality and follow-up 100%. RV parameters were measured offline in accordance with current guidelines. Speckle tracking was derived using the algorithm originally designed for the left ventricle. During follow-up (median: 39 months) 118 patients (16.8%) died. RV global longitudinal strain (GLS) and RV free wall strain (FWS) remained associated with mortality after multivariable adjustment independent of Tricuspid annular plane systolic excursion (TAPSE) (RV GLS: HR 1.07, 95%CI 1.02-1.13, p=0.010, per 1% decrease) (RV FWS: HR 1.05, 95%CI 1.01-1.09, p=0.010, per 1% decrease). This seemed to be caused by significant associations in men. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics. RV GLS and FWS were associated with mortality in HFrEF patients after multivariable adjustment independent of TAPSE. TAPSE, however, remained as the strongest prognosticator in women. More research is needed to identify whether speckle tracking could be superior to conventional RV measures in identifying HFrEF patients with poor outcome.

The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C.Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers.Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%.Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

Current concept in the diagnosis, treatment and rehabilitation of patients with congestive heart failure.

Heart failure (HF) is a major public health problem with a prevalence of 1%-2% in developed countries. The underlying pathophysiology of HF is complex and as a clinical syndrome is characterized by various symptoms and signs. HF is classified according to left ventricular ejection fraction (LVEF) and falls into three groups: LVEF ≥ 50% - HF with preserved ejection fraction (HFpEF), LVEF < 40% - HF with reduced ejection fraction (HFrEF), LVEF 40%-49% - HF with mid-range ejection fraction. Diagnosing HF is primarily a clinical approach and it is based on anamnesis, physical examination, echocardiogram, radiological findings of the heart and lungs and laboratory tests, including a specific markers of HF - brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide as well as other diagnostic tests in order to elucidate possible etiologies. Updated diagnostic algorithms for HFpEF have been recommended (H2FPEF, HFA-PEFF). New therapeutic options improve clinical outcomes as well as functional status in patients with HFrEF (e.g., sodium-glucose cotransporter-2 - SGLT2 inhibitors) and such progress in treatment of HFrEF patients resulted in new working definition of the term “HF with recovered left ventricular ejection fraction”. In line with rapid development of HF treatment, cardiac rehabilitation becomes an increasingly important part of overall approach to patients with chronic HF for it has been proven that exercise training can relieve symptoms, improve exercise capacity and quality of life as well as reduce disability and hospitalization rates. We gave an overview of latest insights in HF diagnosis and treatment with special emphasize on the important role of cardiac rehabilitation in such patients.

ADDition of DAPAgliflozin, Sodium-Glucose Cotransporter-2 Inhibitor to Angiotensin Receptor Blocker-Neprilysin Inhibitors Non-Responders in Patient with Refractory Heart Failure with Reduced Ejection Fraction (ADD DAPA trial)

ObjectivesWe evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. MethodsWe performed a retrospective analysis of 104 symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the optimal GDMT, dapagliflozin, SGLT2i was added inpatients withrefractory heart failure. At 6-months follow-up, the primary outcome was change in left ventricular ejection fraction, and secondary outcomes included changes in NYHA functional class, vital parameters, renal function, potassium levels, and NT-pro BNP levels. ResultsThe primary outcomeat 6-months follow-up was a mean change in left ventricular ejection fraction (LVEF) +9.00 ± 0.62 (p < 0.001). The secondary outcome was a significant improvement (69%) in median NYHA functional class by 2.3 (95% Confidence interval 2.245–2.355) with 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II.Diabetic subgroup reached the HbA1C goal of <7%. None of them had either symptomatic hypotension, hypoglycaemia, dyselectrolaemia, and decline in renal function. The drug was well received by most of the patients. ConclusionsDapagliflozin, an SGLT2i, should be used in symptomatic, refractory HFrEF patients despite the use of ARNI. The combination of ARNI and SGLT2i is well tolerated, but large, randomized trials are needed to prove this hypothesis.

Heart Failure Etiology in Patients Undergoing Cardiac Resynchronization Therapy: Is It Relevant?

Background: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction (HfrEF). Etiology may influence the outcome of patients undergoing CRT. Objective: to evaluate whether etiology (ischemic vs non-ischemic) influences the response to CRT and overall outcome. Methods: Our study included HFrEF patients undergoing CRT between January 2017-November 2019. We assessed right ventricle (RV) and left ventricle (LV) function using transthoracic echocardiography at baseline and one year after CRT. The response to CRT was defined by a decrease of more than 15% of left ventricle systolic volume. Patients were divided in two groups: ischemic and non-ischemic based on personal history. Adverse events (HF related hospitalizations and deaths) were tracked for 33± 12.8 months. Results: 52 patients undergoing CRT were included (64±13.5 years, 55.7% male, 70% non-ischemic etiology) The two groups were similar considering LV systolic baseline parameters and volumes. Ischemic etiology was associated with non-LBBB morphology on ECG (p=0.03), a more severe LV diastolic dysfunction using E/e ratio (p&lt;0.05), and a more severe RV dysfunction using TAPSE (p=0.008) and RV fractional area change (FAC) (p&lt;0.05). There was no significant difference in CRT response between ischemic and non-ischemic etiology. 14 (26.9%) patients had events (10 hospitalizations and 4 deaths) with a higher prevalence in the ischemic group (58.33% vs 25%, p=0.01). Univariate Cox regression analysis reported a higher risk of cardiovascular events for ischemic etiology (HR 2.4, 95% CI [0.8-8.1], p &lt;0.05). In our cohort there was no significant difference in use of an implantable cardioverter-defibrillator in addition to CRT between ischemic and non-ischemic group (64.2% respectively 63.3%, p =0.3). Conclusion: Our study shows that ischemic and nonischemic HF patients had similar response to CRT. However, ischemic etiology was associated with a higher risk ofadverse cardiovascular events and a worse RV systolic dysfunction at baseline.

Prognostic significance of liver stiffness assessed by fibrosis‐4 index in patients with heart failure

BackgroundHeart failure (HF)‐related congestive hepatopathy is a well‐recognized problem in management of HF. The fibrosis‐4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF.Methods and resultsConsecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid‐range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3–2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan–Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients.Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03–1.15, P = 0.001).ConclusionsThe FIB4 index was a significant predictor for total cardiovascular events in HFpEF.

Psychosocial factors, mental health, and coordination capacity in patients with heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction.

AimsPatients with heart failure (HF) suffer from reduced quality‐of‐life (QoL). We aimed to compare QoL, depression, and anxiety scores among outpatients with preserved (HFpEF) and reduced (HFrEF) ejection fraction and non‐HF controls and its relationship to coordination capacity.Methods and resultsFifty‐five participants were recruited prospectively at the University Hospital Jena, Germany (17 HFpEF, 18 HFrEF, and 20 non‐HF controls). All participants underwent echocardiography, cardiopulmonary exercise testing (CPET), 10 m walking test (10‐MWT), isokinetic muscle function and coordination tests, and QoL assessments using the short form of health survey (SF‐36), and hospital anxiety and depression scale (HADS). Furthermore, inflammatory biomarkers such as growth differentiation factor‐15 (GDF‐15) were assessed. Patients with HFpEF showed compared with HFrEF and non‐HF controls reduced QoL [mental component score (MCS): 43.6 ± 7.1 vs. 50.2 ± 10.0 vs. 50.5 ± 5.0, P = 0.03), vitality (VT): 47.5 ± 8.4 vs. 53.6 ± 8.6 vs. 57.1 ± 5.2, P = 0.004), and elevated anxiety (6.5 ± 3.2 vs. 3.3 ± 2.8 vs. 3.8 ± 2. 8, P = 0.02) and depression scores (6.5 [3.5–10.0] vs. 3.0 [1.0–6.5] vs. 2.0 [0.75–3.0], P = 0.01)]. After adjusting to multiple comparisons, anxiety remained higher in HFpEF patients compared with HFrEF (ppost‐hoc = 0.009). HFpEF and HFrEF patients showed reduced coordination capacity compared with non‐HF controls (P < 0.05). In a logistic regression, the presence of depression score ≥8 remained an independent factor for predicting reduced coordination capacity after adjusting for peak VO2, GDF‐15, 10‐MWT, physical component score (PCS), and peak torque of the leg [odds ratio (OR): 0.1, 95% confidence interval (CI): 0.004–0.626, P = 0.02].ConclusionOutpatients with HFpEF had worse QoL and higher anxiety and depression scores compared with HFrEF and non‐HF controls. Depression is associated with reduced QoL and is an independent predictor for reduced coordination capacity.

The value of c-reactive protein to albumin ratio in predicting long term mortality among hfref patients with implantable cardiac defibrillators

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with heart failure with reduced ejection fraction (HFrEF) who received implantable cardiac defibrillator (ICD) still remain at high risk due to pump failure and comorbid conditions. C-reactive protein to albumin ratio (CAR) may be of value for identifying those with high risk for mortality despite ICD implantation. Methods Those who were implanted ICD for HFrEF in our institution between 2009 and 2019 were included. CAR was calculated as ratio of C-reactive protein (CRP) to serum albumin concentration. Patients were grouped into tertiles in accordance to CAR at the time of implantation. After follow up of 48 ± 35 months, survival times of tertiles were compared by using Kaplan-Meier survival method. Results Thousand and eleven patients constituted study population. Ischemic cardiomyopathy was primary diagnosis in 92.3%. Of those 14.5% had died after discharge. Patients in tertile 3 (T3) had higher risk of appropriate shock (19.3% vs 23.7% vs 38.0%) and mortality (4.2% vs 11.0% vs 28.5%) compared to those in other tertiles. Multivariable analysis revealed that when patients in T1 were considered as reference, both those in T2 and T3 had independently higher risk of appropriate shocks and mortality. These effects were consistent in the unadjusted and adjusted multivariable models. Conclusion Among patients with HFrEF and ICD, elevated CAR increased the risk of appropriate device shock and mortality at long term. Table 1Admission C-reactive protein/Albumin ratio (n = 1011)T1 (n = 337)T2 (n = 337)T3 (n = 337)Mortality, %4.211.028.5Mortality, HR (95% CI)Model 1: unadjusted1[Reference]3.85 (2.12 - 11.20)8.14 (2.46 - 28.56)Model 2: adjusted for age, sex1[Reference]3.20 (1.90 - 9.48)6.32 (2.12 - 20.12)Model 3: adjusted for comorbiditesa1[Reference]4.85 (2.06 - 14.12)10.86 (4.12 - 44.82)Model 4: adjusted for covariatesb1[Reference]2.72 (1.66 - 7.12)5.72 (2.04 - 18.05)Frequency, %19.323.738.0Appropriate shock, HR (95% CI)Model 1: unadjusted1[Reference]1.38 (0.44 - 6.88)2.48 (1.34 - 5.82)Model 2: adjusted for age, sex1[Reference]1.42 (0.48 - 7.24)3.02 (1.52 - 6.24)Model 3: adjusted for comorbiditesa1[Reference]1.34 (0.38 - 6.66)2.74 (1.40 - 7.28)Model 4: adjusted for covariatesb1[Reference]1.30 (0.34 - 5.68)2.28 (1.16 - 8.28)Cox proportional analysis and logistic regression models for the appropriate shock and the long-term mortality by CAR.Abstract Figure 1

Heart failure with mid-range ejection fraction and the effect of β-blockers after acute myocardial infarction.

There is currently an ongoing debate about the 'grey area' of heart failure with mid-range ejection fraction (HFmrEF). We evaluated characteristics, prognosis, and the effect of β-blockers on clinical outcomes in patients with HFmrEF after acute myocardial infarction (AMI). We included a total of 10,785 patients and divided them into three groups: EF 40-49% (HFmrEF; n = 2717; reference); EF < 40% (reduced EF [HFrEF]; n = 1194); and EF ≥ 50% (preserved EF [HFpEF]; n = 6874). The primary outcome was 2-year all-cause mortality. HFmrEF was intermediate between HFrEF and HFpEF for baseline characteristics. The risk of all-cause mortality was lower for HFmrEF patients compared to HFrEF patients (adjusted hazard ratio [HR] 0.710; 95% confidence interval [CI] 0.544-0.927; P = 0.012). However, HFmrEF patients tended to be at higher risk for 2-year all-cause mortality than HFpEF patients (adjusted HR 1.235; 95% CI 0.989-1.511; P = 0.090). β-blockers were associated with reductions in all-cause mortality for the entire cohort (adjusted HR 0.760; 95% CI 0.592-0.975; P = 0.031). β-blockers were effective in patients with HFrEF (adjusted HR 0.667; 95% CI 0.471-0.944; P = 0.022), tended to be effective in patients with HFmrEF (adjusted HR 0.665; 95% CI 0.426-1.038; P = 0.072), but not effective in patients with HFpEF (adjusted HR 0.852; 95% CI 0.548-1.326; P = 0.478; interaction P = 0.026). In conclusion, clinical profiles and prognosis of patients with post-AMI HFmrEF are largely intermediate between HFrEF and HFpEF. β-blockers reduced or tended to reduce 2-year all-cause mortality in patients with HFrEF or HFmrEF, respectively, but not those with HFpEF after AMI.

Impact of diastolic dysfunction on outcome in heart failure patients with mid-range or reduced ejection fraction.

AimsThe role of diastolic dysfunction (DD) in prognostic evaluation in heart failure (HF) patients with impaired systolic function remains unclear. We investigated the impact of echocardiography‐defined DD on survival in HF patients with mid‐range (HFmrEF, EF 41–49%) and reduced ejection fraction (HFrEF, EF < 40%).Methods and resultsA total of 2018 consecutive hospitalized HF patients were retrospectively included and divided in two groups based on baseline EF: HFmrEF group (n = 951, aged 69 ± 13 years, 74.2% male) and HFrEF group (n = 1067, aged 68 ± 13 years, 76.3% male). Clinical data were collected and analysed. All patients completed ≥1 year clinical follow‐up. The primary endpoint was defined as all‐cause death (including heart transplantation) and cardiovascular (CV)‐related death. All‐cause mortality (30.8% vs. 24.9%, P = 0.003) and CV mortality (19.1% vs. 13.5%, P = 0.001) were significantly higher in the HFrEF group than the HFmrEF group during follow‐up [median 24 (13–36) months]. All‐cause mortality increased in proportion to DD severity (mild, moderate, and severe) in either HFmrEF (17.1%, 25.4%, and 37.0%, P < 0.001) or HFrEF (18.9%, 30.3%, and 39.2%, P < 0.001) patients. The risk of all‐cause mortality [hazard ratio (HR) = 1.347, P = 0.015] and CV mortality (HR = 1.508, P = 0.007) was significantly higher in HFrEF patients with severe DD compared with non‐severe DD after adjustment for identified clinical and echocardiographic covariates. For HFmrEF patients, severe DD was independently associated with increased all‐cause mortality (HR = 1.358, P = 0.046) but not with CV mortality (HR = 1.155, P = 0.469).ConclusionsEchocardiography‐defined severe DD is independently associated with increased all‐cause mortality in patients with HFmrEF and HFrEF.