Symptomatic Systolic Heart Failure Research Articles

Transition from asymptomatic to symptomatic systolic chronic heart failure: rationale and design of TransitionCHF.

Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials. TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease

BackgroundEvidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. ObjectivesThis study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. MethodsBoth CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. ResultsIn total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. ConclusionsIn pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

Frequency of Iron Deficiency in Heart Failure Patients

Background: People suffering from heart failure frequently face iron deficiency, which has been linked to higher mortality and more frequent hospital stays. People with symptomatic systolic heart failure and iron deficiency, iron supplementation significantly decreased the risk of hospitalization for heart failure and the combined endpoint of hospitalization for heart failure and mortality, Aim: This research sought to determine the prevalence of iron insufficiency in people with chronic heart failure. Design of the study: This study is cross-sectional. Place of the study: Ayub Teaching Hospital Abbottabad from November 2019 to April 2020. Methodology: After obtaining written informed permission, the research participants who met the inclusion criteria were chosen. Patients between the ages of 40 and 70, of either gender, were included in the research group if they had a documented history of CHF for less than six months and an echocardiogram showed an LVEF of less than 45%. Results: Mean age of the patients was 55.79±9.926, ranging from 40 to 70 years and the mean BMI was 29.03±5.043 ranging from 19 to 49kg/m2, mean serum ferritin level was 226.03±160.297 ranging from 70 to 500μg/L and mean transferrin saturation was 23.15±6.449 ranging from 15 to 38%. In the frequency of heart failure, patients of heart failure were 72(48%) and 78(52%) had no HF. In the frequency of iron deficiency, patients found with a deficiency were 82(54.7%) and 68(45.3%) had no deficiency. Practical Implication: Patients with heart failure should have routine iron deficiency screenings regardless of the presence of anaemia or abnormal RCI. In order to improve risk-based selection of participants who are frequently not at risk for iron deficiency Conclusion: Men with functional classes II–III were more likely to have iron deficiency anaemia (72% prevalence). Hypertension was the most prevalent comorbidity. Keywords: Iron deficiency, Heart failure, Anemia

Cardiac Resynchronization Therapy: current guidelines and recent advances beyond drug treatment.

Cardiac resynchronization therapy (CRT) is the therapy of choice for patients with symptomatic systolic heart failure (HF) and left bundle branch block (LBBB), despite optimal medical therapy (OMT). The recently published 2021 European Society of Cardiology (ESC) Guidelines on cardiac pacing and cardiac resynchronization therapy highlight the importance of CRT on top of OMT in HF patients with left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm and typical LBBB with QRS duration ≥150ms. In the presence of medically intractable or recurrent after catheter ablation atrial fibrillation (AF), AV nodal ablation as an adjuvant therapy becomes more relevant in patients qualifying for the implantation of a biventricular system. Furthermore, CRT may be considered in cases when increased pacing of the right ventricle is not desirable. However, alternative pacing sites and strategies are currently available, if the CRT is not feasible and effective in patients. However, strategies targeting "multi-sides" or using "multi-leads" have shown superiority over classic CRT. On the other hand, conduction system pacing seems to be a promising technique. Although early results are positive, consistency during the long term is pending. The indication for additional defibrillation therapy (ICD) may occasionally be unnecessary and has to be considered individually. Due to the great development and success of heart failure drug therapy, its positive effect on LV function can lead to enormous improvement. Physicians must await these effects and findings, which hopefully could lead to a relevant LV improvement resulting in a definitive decision against an ICD.

Impact of prediabetes and type 2 diabetes mellitus on cardiac function in the general population

Abstract Introduction Prediabetes and type 2 diabetes mellitus (T2DM) are risk factors for heart failure (HF). The association of prediabetes and T2DM to different forms of functional left ventricular impairment and their impact on clinical outcome in the general population needs to be further investigated. In this context, little is known about the prevalences of prediabetes and different HF subtypes in the general population, especially in Europe. Purpose To investigate the prevalence and clinical impact of prediabetes and type 2 diabetes mellitus (T2DM) on functional cardiac disorder (FCD). Methods The participants of the Gutenberg Health Study sample (15,010 subjects, 35–74 years) were stratified in individuals with euglycaemia, prediabetes and T2DM based on clinical information and HbA1c level. FCD included asymptomatic systolic and diastolic dysfunction, symptomatic systolic and diastolic heart failure, asymptomatic diastolic dysfunction and preserved left ventricular ejection fraction (EF), asymptomatic diastolic dysfunction and reduced EF, asymptomatic preserved diastole and reduced EF, symptomatic heart failure with preserved EF (HFpEF) and symptomatic heart failure with reduced EF HFrEF). Using structured follow-up clinical outcome was assessed. Results Overall, 14,870 individuals were included in the present analysis. Among them, 9,426 individuals were categorized in the euglycaemia group, 4,128 participants had prediabetes and in 1,316 individuals T2DM was present. Prevalence of FCD increased from euglycaemia (19.6%) over prediabetes (33.3%) to T2DM (46.8%, p&amp;lt;0.0001). Prevalence of symptomatic HF was increased in patients with T2DM (euglycaemia 2.8%, prediabetes 5.9%, T2DM 11.9%). T2DM was associated with reduced EF (β −0.63, 95% CI −0.99 to −0.26, P=0.00088) and elevated E/E' (β 0.08, 95% CI 0.06 to 0.10, P&amp;lt;0.0001), whereas prediabetes was associated to elevated E/E' (β 0.02, 95% CI 0.01 to 0.03, P=0.0029). Prediabetes and T2DM revealed increased prevalences of FCD (13%, 18%), asymptomatic diastolic dysfunction with preserved EF (prediabetes: 14%, T2DM: 11%), symptomatic heart failure (prediabetes: 46%, T2DM: 70%) and HFpEF (prediabetes: 49%, T2DM: 82%). With prediabetes and T2DM all-cause mortality was elevated in presence and absence of FCD, only T2DM was also a risk factor for cardiovascular mortality with and without FCD. Within a 5-years follow-up, T2DM was an independent risk factor for the development of FCD, asymptomatic diastolic dysfunction with reduced ejection fraction, symptomatic heart failure and HFrEF. Prediabetes was not an independent risk factor for FCD. Conclusions In the general population, a high prevalence of asymptomatic FCD is present. Coexisting FCD and prediabetes as well as T2DM result in increased mortality elucidating the need for early detection and prevention of DM development, especially with regard to numerous asymptomatic people concerned. T2DM, but not prediabetes, is a risk factor for incident FCD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The Gutenberg Health Study is supported by the government of Rheinland-Pfalz (`Stiftung Rheinland-Pfalz für Innovation'), the research programmes `Wissen schafft Zukunft' and the Centre forTranslational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, Germany, and its contract with Boehringer Ingelheim and Philips Medical Systems including an unrestricted grant forthe Gutenberg Health Study. P.S.W. and J.H.P. are funded by the Federal Ministry of Education and Research (BMBF 01EO1503). P.S.W. and T.M. are principal investigators of the German Center for Cardiovascular Research (DZHK). P.S.W. is principal investigator of the DIASyM research core (BMBF 161L0217A).

Comparable Efficacy in Ischemic and Non-Ischemic ICD Recipients for the Primary Prevention of Sudden Cardiac Death.

(1) Background: In patients suffering from heart failure, the main causes of death are either hemodynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extent from these devices. (2) Methods: The primary outcome of this single-center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients—symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death—were included retrospectively: 59% ischemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP) patients. Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not significantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 patients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95% confidence interval (CI) 0.45 to 2.28; p = 0.97). All-cause mortality occurred in 14 of 166 patients (8.4%) in the NICMP group and 18 of 237 patients (7.6%) in the ICMP group. Sudden cardiac death occurred in two patients (1.2%) in the NICMP group and in four patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; p = 0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusions: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovascular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Focal Segmental Glomerulosclerosis Presenting as Acute Systolic Heart Failure

Cardiomyopathies are present in many forms and are the result of numerous etiologies with one well-established etiology being chronic kidney disease (CKD). With recent discoveries linking early stages of CKD to profound cardiovascular disease (ischemic or non-ischemic cardiomyopathy), our focus has shifted to a seemingly inexplicable link between focal segmental glomerulosclerosis (FSGS) and non-ischemic cardiomyopathy. The cardiovascular and renal organ systems possess a unique relationship which we presume to be a bi-directional association of cause-and-effect. We present two cases in which our patients, with underlying FSGS, present with signs and symptoms of systolic heart failure.

18F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic systolic heart failure patients

Abstract Background/Introduction Depression comorbidity is an important issue in heart failure (HF) disease. Results from the recent prospective randomized trial MOOD-HF did not provide a rationale for the indiscriminate use of antidepressants in depressed HF patients. Purpose The study investigated whole-brain and regional-brain glucose metabolism in HF patients with 18F-FDG PET/CT and its association with depression comorbidity. Methods Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF&amp;lt;40%), NYHA class II-IV and mean age of 55.5±12.0 years participated in the study. All patients had echocardiography, blood sampling, HF-adapted and psychometric questionnaires before discharge and a brain 18F-FDG PET/CT scan after discharge. Semi-automated PET/CT image analysis was performed on all patients and 30 matched controls. The metabolic index SUVmean was calculated for the whole-brain and three brain regions (prefrontal cortex, amygdala and hippocampus), implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing depression-related regional-brain SUVmean with the whole-brain SUVmean. Results HF patients had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001), average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p&amp;lt;0.001) and average standardized SUVmean (1.28±0.60 vs 2.07±1.32, p&amp;lt;0.001) compared to controls. Whole-brain SUVmean had a statistically significant correlation to patient age (r=−0.39, p=0.031), NYHA class (p=0.027), LVEF in the major group of 21 NYHA III-IV patients (p=0.018), diabetes comorbidity (p=0.001), creatinine levels (r=−0.49, p=0.005) and depression (r=−0.36, p=0.049). Regional-brain SUVmean was correlated to whole-brain SUVmean (r=0.53, p=0.002) and depression (r=0.46, p=0.011). The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (&amp;gt;0.93) or “real” (≤0.93) depression. Conclusion HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT scan, which is consistent with impaired cerebral perfusion. Depressed HF patients (Beck Depression Inventory score &amp;gt;13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression. Absence of whole-brain hypometabolism suggested “real” depression. When the pattern of whole-brain hypometabolism included significant relative, depression-related regional hypometabolism (standardized SUVmean ≤0.93), “real” depression was the most likely diagnosis. The distinction is important, as different types of comorbid depression suggest different treatment approach. Summarizing figure Funding Acknowledgement Type of funding source: None

Coronary and aortic calcification are associated with cardiovascular events on immune checkpoint inhibitor therapy

BackgroundAlthough the incidence of immune checkpoint inhibitor (ICI)-related cardiovascular (CV) toxicity is low, the overall burden of CV events after ICI is unknown. Risk factors for CV events after ICI have yet to be identified. ObjectivesWe sought to evaluate the association between vascular calcification on routine baseline computed tomography (CT) imaging and CV events following ICI. MethodThis was a single-center, retrospective cohort study of 76 patients referred to Cardio-Oncology with prior ICI treatment. Coronary and aortic calcification on non-gated chest and abdominal CT imaging were qualitatively assessed. The association of baseline clinical parameters and vascular calcification with symptomatic heart failure (HF), acute coronary syndrome, myocarditis, symptomatic arrhythmia, or pericardial effusion after ICI was evaluated. ResultsOver 11 months of follow-up, there were 80 CV events that occurred in 49 patients. Worse coronary and aortic calcification on pre-treatment CT imaging was seen in patients with a CV event (p = .018 and p = .014, respectively). There were no differences in traditional CV risk factors between those with and without a CV event. Eighteen patients (37%) were restarted on ICI therapy after a non- myocarditis or symptomatic systolic HF CV event without recurrent events or mortality over 13 months of follow-up. ConclusionsSymptomatic HF was the most common CV event seen after ICI therapy. Worse coronary and aortic calcification on baseline CT imaging was associated with CV events following ICI. With careful clinical evaluation, selected patients may be re-treated with ICI following a non- myocarditis or symptomatic systolic HF CV event.

18 F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic heart failure patients with impaired systolic function.

Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional brain glucose metabolism in HF patients and its association with depression comorbidity. Twenty-nine hospitalized patients with symptomatic systolic HF (left ventricular ejection fraction <40%), New York Heart Association (NYHA) class II-IV and mean age of 55.5 ± 12.0 years, had psychometric questionnaires before discharge and an 18 F-FDG PET/CT brain scan after discharge. Semi-automated image analysis was performed on all cases and 30 matched controls. The metabolic parameter mean standardized uptake value (SUVmean ) was calculated for the whole brain and three brain regions implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing regional brain SUVmean with whole-brain SUVmean . Cases had lower average whole-brain SUVmean (3.90 ± 1.49 vs. 5.10 ± 1.35, P=0.001) and average regional brain SUVmean (4.57 ± 2.31 vs. 9.96 ± 3.58, P < 0.001) compared to controls. Whole-brain SUVmean had a significant correlation with patient age, NYHA class, diabetes, creatinine levels, depression, and cognitive impairment. Regional brain SUVmean was correlated with whole-brain SUVmean and depression. The standardized SUVmean , in particular, was found to be a robust index that could differentiate HF patients with 'epiphenomenal' (>0.93) or 'real' (≤0.93) depression. Heart failure patients with more severe disease showed whole-brain and regional brain hypometabolism in 18 F-FDG PET/CT. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between 'epiphenomenal' and 'real' depression. Namely, presence of whole-brain hypometabolism suggested 'epiphenomenal' depression, whereas absence suggested 'real' depression. Presence of significant relative regional brain hypometabolism enhanced the likelihood of 'real' depression diagnosis.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients

Background - Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis. Methods - This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period. Results - Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant. Conclusions - In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.

Skeletal muscle alterations in tachycardia-induced heart failure are linked to deficient natriuretic peptide signalling and are attenuated by RAS-/NEP-inhibition.

BackgroundHeart failure induced cachexia is highly prevalent. Insights into disease progression are lacking.MethodsEarly state of left ventricular dysfunction (ELVD) and symptomatic systolic heart failure (HF) were both induced in rabbits by tachypacing. Tissue of limb muscle (LM) was subjected to histologic assessment. For unbiased characterisation of early and late myopathy, a proteomic approach followed by computational pathway-analyses was performed and combined with pathway-focused gene expression analyses. Specimen of thoracic diaphragm (TD) served as control for inactivity-induced skeletal muscle alterations. In a subsequent study, inhibition of the renin-angiotensin-system and neprilysin (RAS-/NEP) was compared to placebo.ResultsHF was accompanied by loss of protein content (8.7±0.4% vs. 7.0±0.5%, mean±SEM, control vs. HF, p<0.01) and a slow-to-fast fibre type switch, establishing hallmarks of cachexia. In ELVD, the enzymatic set-up of LM and TD shifted to a catabolic state. A disturbed malate-aspartate shuttle went well with increased enzymes of glycolysis, forming the enzymatic basis for enforced anoxic energy regeneration. The histological findings and the pathway analysis of metabolic results drew the picture of suppressed PGC-1α signalling, linked to the natriuretic peptide system. In HF, natriuretic peptide signalling was desensitised, as confirmed by an increase in the ratio of serum BNP to tissue cGMP (57.0±18.6pg/ml/nM/ml vs. 165.8±16.76pg/ml/nM/ml, p<0.05) and a reduced expression of natriuretic peptide receptor-A. In HF, combined RAS-/NEP-inhibition prevented from loss in protein content (8.7±0.3% vs. 6.0±0.6% vs. 8.3±0.9%, Baseline vs. HF-Placebo vs. HF-RAS/NEP, p<0.05 Baseline vs. HF-Placebo, p = 0.7 Baseline vs. HF-RAS/NEP).ConclusionsTachypacing-induced heart failure entails a generalised myopathy, preceding systolic dysfunction. The characterisation of “pre-cachectic” state and its progression is feasible. Early enzymatic alterations of LM depict a catabolic state, rendering LM prone to futile substrate metabolism. A combined RAS-/NEP-inhibition ameliorates cardiac-induced myopathy independent of systolic function, which could be linked to stabilised natriuretic peptide/cGMP/PGC-1α signalling.

P5450Evening levels and circadian changes of salivary cortisol predict adverse events in heart failure patients with comorbid depression - a MOOD-HF substudy

Abstract Background Depression is frequent in heart failure (HF) and associated with adverse clinical outcomes. The randomized MOOD-HF trial showed that in depressed patients with systolic heart failure (HF) the selective serotonin reuptake inhibitor escitalopram (E) improved neither survival nor depression compared to placebo (P). The hypothalamic-pituitary-adrenocortical axis is known to be altered in depression or HF. This MOOD-HF substudy aimed to clarify whether circadian salivary cortisol levels (SCL) were predictive of adverse events in depressed MOOD-HF participants and whether outcomes differed according to treatment with E. Methods MOOD-HF participants (all suffering from symptomatic systolic HF with left ventricular ejection fraction (LVEF) &lt;45% and current major depression) were eligible for the present analysis if providing samples for SCL determination (luminescence immunoassay) at baseline visit (BL) and if not on oral glucocorticosteroid therapy. Depression severity was determined with the Montgomery–Åsberg Depression Rating Scale (MADRS) and LVEF measured by echocardiography. Results In the total study cohort (146 patients on E, 147 on P) median morning SCL at BL was 0.210 μg/dL (IQR 0.141–0.338 μg/dL) and median evening (pm) SCL 0.067 μg/dL (0.036–0.128 μg/dL, p&lt;0.001). Median circadian change was 0.124 μg/dL (0.044–0.239 μg/dL). In patients with BL pm-SCL above the median MADRS-score was 21.7±9.1 and LVEF 33.7±8.4% respectively, in patients with pm-SCL below the median these values were 19.6±9.1 and 36.5±7.8% (p=0.048; p=0.004). During 12 months follow-up the composite endpoint (all-cause death or rehospitalization) occurred least in E-treated patients with low pm-SCL and most often in E-treated patients with high pm-SCL (HR 2.02, 95% CI 1.12–3.65, p=0.010); patients on P had comparable event rates irrespective of BL pm-SCL (Figure A). Thus, numerically patients on E with low BL pm-SCL had lower event rates compared with corresponding P-treated patients (HR 0.76 (0.41–1.40, p=0.796)), while patients with high BL pm-SCL had higher event rates (HR 1.29 (0.74–2.24, p=0.799)) than corresponding P-treated patients. Patients with circadian SCL changes above the median receiving P experienced the composite primary endpoint least, while both subgroups with circadian SCL changes below the median and also patients with circadian SCL changes above the median on E had higher event rates (HR 0.66 (0.45–0.97, p=0.039), Figure B). Conclusion In depressed patients with systolic HF high pm-SCL are associated with more severe disease (depression and cardiac dysfunction). Extending primary MOOD-HF results indicating unfavourable outcomes related to E, the current findings suggest a SCL x treatment interaction with higher event rates in (sicker) patients with high pm-SCL and lower event rates in (less sick) patients with low pm-SCL when treated with the antidepressant. Low circadian changes of SCL were always associated with higher event rates. Acknowledgement/Funding BMBF (Grant 01 KG0702) and Lundbeck A/S Denmark

Recovery of complete left bundle branch block following heart failure improvement by left bundle branch pacing in a patient

A 57-year-old male presented with symptomatic systolic heart failure and complete left bundle branch block (LBBB). Left bundle branch pacing corrected LBBB at a low capture threshold (0.5V @0.4ms) with right bundle branch conduction delayand paced QRS morphology changed to near-normal by adjusting AV delay with diminished RBBD. At 1-year follow-up, the patient had a significant improvement in heart failure and LBBB automatically resolved with a rate-dependent pattern. LBBP may be an alternative to conventional cardiac resynchronization therapy with the likelihood of recovery of LBBB. More research is needed to evaluate the potential use of this pacing strategy in patients with LBBB and heart failure.

A Registry-based Cluster Randomized Trial to Compare the Effect of Spironolactone vs. Eplerenone on Clinical Outcomes in Patients With Symptomatic Systolic Heart Failure

A Registry-based Cluster Randomized Trial to Compare the Effect of Spironolactone vs. Eplerenone on Clinical Outcomes in Patients With Symptomatic Systolic Heart Failure

Usefulness of Canakinumab to Improve Exercise Capacity in Patients With Long-Term Systolic Heart Failure and Elevated C-Reactive Protein

Interleukin-1β (IL-1β) is a cytokine involved in atherothrombosis and is known to depress cardiac function. We hypothesized that blocking IL-1β in patients with symptomatic systolic heart failure (HF) would improve their cardiorespiratory fitness. The purpose of the study was to measure changes in peak oxygen consumption (VO2) in 30 patients with prior myocardial infarction, high-sensitivity C-reactive protein ≥ 2 mg/l and HF with left ventricular ejection fraction (LVEF) < 50% enrolled in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) in an independent single center substudy. We measured peak VO2 before and after 3 and 12 months of treatment with Canakinumab every 3 months (50, 150, or 300mg subcutaneously) or placebo, and measured LVEF before and after 12 months. In December 2013, the CANTOS study announced early termination of enrollment, halting enrollment for this substudy after only 15 patients, of which 3 were assigned to placebo and 12 to Canakinumab (50mg [1; 7%], 150mg [5; 33%], 300mg [6; 40%]). Patients treated with Canakinumab had a significant improvement in peak VO2, from 19.2 to 22.8 ml/kg/min at 3 months (p = 0.023 within-group changes, p = 0.026 for time_x_group interaction versus placebo [primary end point]), and an improvement in LVEF 38% (33-43) to 44% (38-52) at 12 months (p = 0.012 for within-group changes). No significant changes were seen in the placebo group. In conclusion, the findings of this small prespecified secondary analysis of the CANTOS trial support the positive results of the overall study, and confirm IL-1 as a potential therapeutic target in HF. https://clinicaltrials.gov/ct2/show/NCT01900600.

Improving the Use of Primary Prevention Implantable Cardioverter-Defibrillators Therapy With Validated Patient-Centric Risk Estimates.

The authors previously developed the Seattle Proportional Risk Model (SPRM) in systolic heart failure patients without implantable cardioverter-defibrillators (ICDs)to predict the proportion of deaths that were sudden. They subsequently validated the SPRM in 2 observational ICD data sets. The objectives in the present study were to determine whether this validated model could improve identification of clinically important variations in the expected magnitude of ICD survival benefit by using a pivotal randomized trial of primary prevention ICD therapy. Recent data show that<50% of nominally eligible subjects receive guideline- recommended primary prevention ICDs. In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a placebo-controlled ICD trial in 2,521 patients with an ejection fraction≤35% and symptomatic heart failure, we tested the use of patient-level SPRM-predicted probability of sudden death (relative to that of non-sudden death) as a summary measurement of the potential for ICD benefit. A Cox proportional hazards model was used to estimate variations in the relationship between patient-level SPRM predictions and ICD benefit. Relative to use of mortality predictions with the Seattle Heart Failure Model, the SPRM was much better at partitioning treatment benefit from ICD therapy (effect size was 2- to 3.6-fold larger for the ICD×SPRM interaction). ICD benefit varied significantly across SPRM-predicted risk quartiles: for all-cause mortality, a+10% increase with ICD therapy in the first quartile (highest risk of death, lowest proportion of sudden death) to a decrease of 66% in the fourth quartile (lowest risk of death, highest proportion of sudden death; p= 0.0013); for sudden death mortality, a 19% reduction in SPRM quartile 1 to 95% reduction in SPRM quartile 4 (p< 0.0001). In symptomatic systolic heart failure patients with a Class I recommendation for primary prevention ICD therapy, the SPRM offers a useful patient-centric tool for guiding shared decision making.

Has the Time Come to Be More Aggressive With Bariatric Surgery in Obese Patients With Chronic Systolic Heart Failure?

Obesity is a strong risk factor for the development of heart failure (HF). Diet, exercise, and weight-loss pharmacotherapies have limited potential to achieve significant and sustainable weight loss, especially in patients with symptomatic systolic HF. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity. Bariatric surgeries such as the laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) represent the most successful long-term strategy for achieving weight loss and diabetes and hypertension remission in the general obese population. These benefits translate to reductions in cardiovascular events and mortality, as well as improvements in myocardial structure and function. There is also now data supporting the safety of LSG or RYGB in patients with systolic dysfunction and a reduction in HF admissions post-operatively. Current literature and clinical experience suggest that the most appropriate bariatric surgery candidates with HF are patients aged < 50-60years, with severely depressed systolic function and NYHA II-III symptoms, who have failed non-surgical strategies and have a high likelihood of future cardiac transplantation candidacy after weight loss. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity.

Cost-Effectiveness of Ivabradine in the Treatment of Chronic Heart Failure

In the Systolic Heart failure treatment with the If inhibitor Trial (SHIFT) randomised placebo-controlled trial, ivabradine was shown to reduce hospital admissions for worsening heart failure (HF) and deaths due to HF in patients with symptomatic systolic HF and an elevated resting heart rate (HR). This analysis evaluates the cost effectiveness of adding ivabradine to optimal standard HF treatment in patients with a HR≥77 bpm. A Markov model was developed to assess the impact of ivabradine on mean survival and quality of life over a patient's lifetime (10 years). The hospitalisation and death rates were calculated using patient-level data from SHIFT. The reduction in quality of life due to HF hospitalisations was estimated directly from EQ-5D data collected in SHIFT. Australian costs were applied to the resource use from SHIFT. The modelled mean increase in survival with ivabradine was 0.115 years. The mean increase in quality-adjusted survival was 0.108 years. The average cost of ivabradine was A$2,957 and the cost savings associated with a reduction in HF hospitalisations was A$1,344. The cost per quality adjusted life year gained (QALYG) was A$14,905. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is likely to be cost-effective in this indication. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is a cost-effective treatment in the Australian setting for HF patients with a HR≥77 bpm on optimal standard therapy with a cost per QALYG similar or lower than that for other publicly funded treatments.