Hospitalization For Worsening Heart Failure Research Articles

The Prognostic Value of Right Ventricular Function in Patients with Chronic Heart Failure-A Prospective Study.

Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800-0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800-0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853-0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy.

Prevalence and prognostic impact of bone disease in chronic heart failure with reduced ejection fraction.

Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction<40% on stable, optimal HFrEF therapy and left ventricular ejection fraction<50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score≤2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P=0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P=0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P=0.011). Osteoporosis was not significantly associated with CV events. In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.

Prognostic significance of right ventricular dysfunction in patients presenting with acute left-sided heart failure.

The prognostic value of right ventricular (RV) function in chronic heart failure (HF) has lately been well established. However, research on its role in acute heart failure (AHF) is sparse. This study comprised 195 patients, aged between 18 and 80years, with acute left-sided heart failure (HF) and a left ventricular ejection fraction (LVEF) < 50%. Patients with LVEF ≥ 50%, mechanical ventilatory or circulatory support, poor echocardiographic windows, prosthetic valves, congenital heart diseases, infective endocarditis, and/or life expectancy < 1year due to non-cardiac causes were excluded. The study participants' mean age was 57.7 ± 10.9years, and 74.9% were males. Coronary artery disease was present in 80.5% of patients. The mean LVEF was 31% ± 8.7. RV dysfunction (RVD), defined as tricuspid annular plane systolic excursion (TAPSE) < 17mm, RV S' < 9.5cm/s and/or RV fractional area change (FAC) < 35%, was identified in 48.7% of patients. The RV was dilated in 67.7% of the patients. RVD was significantly associated with a longer HF duration, atrial fibrillation, and idiopathic dilated cardiomyopathy. The primary outcome, a 6-month composite of cardiovascular death or hospitalization for worsening HF (HHF), occurred in 42% of the participants. Cardiovascular mortality and HHF occurred in 30.5% and 23.9% of the patients, respectively. The primary endpoint and longer CCU stays were significantly more common in patients with RVD than in those with normal RV function. RV dilatation was significantly associated with the primary outcome, whether alone or in combination with RVD. Multivariate regression analysis showed that only RV global longitudinal strain (GLS) independently predicted poor outcomes. RVD and RV dilatation strongly predict CV death and HHF in patients with AHF and LVEF < 50%. Multivariate analysis showed that RV GLS was the only predictor of a composite of CV death and HHF.

Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events: A Post Hoc Analysis of SOLOIST-WHF

BackgroundApproximately 25% of patients admitted to hospitals for worsening heart failure (WHF) are readmitted within 30 days. ObjectivesThe authors conducted a post hoc analysis of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-WHF) trial to evaluate the efficacy of sotagliflozin versus placebo to decrease mortality and HF-related events among patients who began study treatment on or before discharge from their index hospitalization. MethodsThe main endpoint of interest was cardiovascular death or HF-related event (HF hospitalization or urgent care visit) occurring within 90 and 30 days after discharge for the index WHF hospitalization. Treatment comparisons were by proportional hazards models, generating HRs, 95% CIs, and P values. ResultsOf 1,222 randomized patients, 596 received study drug on or before their date of discharge. Sotagliflozin reduced the main endpoint at 90 days after discharge (HR: 0.54 [95% CI: 0.35-0.82]; P = 0.004) and at 30 days (HR: 0.49 [95% CI: 0.27-0.91]; P = 0.023) and all-cause mortality at 90 days (HR: 0.39 [95% CI: 0.17-0.88]; P = 0.024). In subgroup analyses, sotagliflozin reduced the 90-day main endpoint regardless of sex, age, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, or mineralocorticoid receptor antagonist use. Sotagliflozin was well-tolerated but with slightly higher rates of diarrhea and volume-related events than placebo. ConclusionsStarting sotagliflozin before discharge in patients with type 2 diabetes hospitalized for WHF significantly decreased cardiovascular deaths and HF events through 30 and 90 days after discharge, emphasizing the importance of beginning sodium glucose cotransporter inhibitor treatment before discharge.

Real-Life Data on Readmissions of Worsening Heart Failure Outpatients in a Heart Failure Clinic.

Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019. The patients were followed for one year and were on optimized therapy. The inclusion criteria for the study were patients who had been hospitalized and subsequently discharged at least three months prior to their enrollment. Patient demographics, heart failure (HF) characterization, comorbidities, pharmacological treatment, treatments of decompensated HF in the day hospital (DH), hospitalizations for WHF, and death were recorded. We applied logistic regression analysis to assess predictors of hospital readmission for HF. Results A total of 351 patients were included: 90 patients (26%) had WHF requiring treatment with intravenous diuretics in the DH; 45 patients (mean age: 79.1 ± 9.0 years) were readmitted for decompensated HF within one year (12.8%) with no gender difference, while 87.2% of the patients (mean age: 74.9 ± 12.1 years) were never readmitted. Readmitted patients were significantly older than those who were not (p=0.031). Additionally, they had a higher New York Heart Association (NYHA) functional classification (p<.001), were on a higher daily dose of furosemide (p=0.008) at the time of the inclusion visit, were more frequently affected by the chronic obstructive pulmonary disease (COPD) (p=0.004); had been treated more often in the DH for WHF (p<.001) and had a higher mortality rate (p<.001) at one year. Conclusions This study aimed to determine WHF patient readmission rates and predictors. According to our results, a higher NYHA class, the need for treatment in the DH for WHF, a daily dose of furosemide equal to or greater than 80 mg, and COPD were predictors of readmission for WHF. CHF patients continue to experience WHF and recurrent hospitalizations despite therapeutic advances and close follow-up in the HFC with the multidisciplinary team. Besides COPD, the HF readmission risk factors found were mainly related to advanced disease. Furthermore, the structured and multidisciplinary approach of our disease management program likely contributed to our relatively low rate of readmissions.

A European multinational cost-effectiveness analysis of empagliflozin in heart failure with reduced ejection fraction

PurposeThis research examined the cost-effectiveness of adding empagliflozin to standard of care (SoC) compared with SoC alone for treatment of heart failure with reduced ejection fraction (HFrEF) from the perspective of healthcare payers in the United Kingdom (UK), Spain and France.MethodsA lifetime Markov cohort model was developed to simulate patients’ progression through health states based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The model predicted risk of death, hospitalisation for worsening heart failure (HHF), treatment-related adverse events, and treatment discontinuation each monthly cycle. Clinical inputs and utilities were derived from EMPEROR-Reduced trial data, supplemented by published literature and national costing databases. Costs (2021 pound sterling/euro) and quality-adjusted life-years (QALYs) were discounted annually for the UK (3.5%), Spain (3.0%) and France (2.5%).ResultsIn the UK, Spain and France, empagliflozin plus SoC yielded additional QALYs (0.19, 0.23 and 0.21) at higher cost (£1185, €1770 and €1183 per patient) than SoC alone, yielding incremental cost-effectiveness ratios of £6152/QALY, €7736/QALY and €5511/QALY, respectively. Reduced HHF incidence provided most cost offsets for empagliflozin plus SoC. Similar results were obtained for a range of subgroups and sensitivity analyses. Probabilistic sensitivity results indicated empagliflozin plus SoC remained cost-effective vs. SoC at willingness-to-pay thresholds of £20,000/QALY, €20,000/QALY and €30,000/QALY in 79.6%, 75.5% and 97.3% of model runs for the UK, Spain and France, respectively.ConclusionsEmpagliflozin added to SoC leads to health benefits for patients with HFrEF and is a cost-effective treatment option for payers in multiple European countries (UK, Spain, France).

Analysis of Worsening Heart Failure Events in an Integrated Health Care System

BackgroundThere is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity. ObjectivesThe purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations. MethodsWe studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing. ResultsWe identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations. ConclusionsED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.

A Natural Language Processing–Based Approach for Identifying Hospitalizations for Worsening Heart Failure Within an Integrated Health Care Delivery System

The current understanding of epidemiological mechanisms and temporal trends in hospitalizations for worsening heart failure (WHF) is based on claims and national reporting databases. However, these data sources are inherently limited by the accuracy and completeness of diagnostic coding and/or voluntary reporting. To assess the overall burden of and temporal trends in the rate of hospitalizations for WHF. This cohort study, performed from January 1, 2010, to December 31, 2019, used electronic health record (EHR) data from a large integrated health care delivery system. Calendar year trends. Hospitalizations for WHF (ie, excluding observation stays) were defined as 1 symptom or more, 2 objective findings or more including 1 sign or more, and 2 doses or more of intravenous loop diuretics and/or new hemodialysis or continuous kidney replacement therapy. Symptoms and signs were identified using natural language processing (NLP) algorithms applied to EHR data. The study population was composed of 118 002 eligible patients experiencing 287 992 unique hospitalizations (mean [SD] age, 75.6 [13.1] years; 147 203 [51.1%] male; 1655 [0.6%] American Indian or Alaska Native, 28 451 [9.9%] Asian or Pacific Islander, 34 903 [12.1%] Black, 23 452 [8.1%] multiracial, 175 840 [61.1%] White, and 23 691 [8.2%] unknown), including 65 357 with a principal discharge diagnosis and 222 635 with a secondary discharge diagnosis of HF. The study population included 59 868 patients (20.8%) with HF with a reduced ejection fraction (HFrEF) (<40%), 33 361 (11.6%) with HF with a midrange EF (HFmrEF) (40%-49%), 142 347 (49.4%) with HF with a preserved EF (HFpEF) (≥50%), and 52 416 (18.2%) with unknown EF. A total of 58 042 admissions (88.8%) with a primary discharge diagnosis of HF and 62 764 admissions (28.2%) with a secondary discharge diagnosis of HF met the prespecified diagnostic criteria for WHF. Overall, hospitalizations for WHF identified on NLP-based algorithms increased from 5.2 to 7.6 per 100 hospitalizations per year during the study period. Subgroup analyses found an increase in hospitalizations for WHF based on NLP from 1.5 to 1.9 per 100 hospitalizations for HFrEF, from 0.6 to 1.0 per 100 hospitalizations for HFmrEF, and from 2.6 to 3.9 per 100 hospitalizations for HFpEF. The findings of this cohort study suggest that the burden of hospitalizations for WHF may be more than double that previously estimated using only principal discharge diagnosis. There has been a gradual increase in the rate of hospitalizations for WHF with a more noticeable increase observed for HFpEF.

P893 Left ventricular flow energetics predicts worsening heart failure in dilated cardiomyopathy

Abstract Background Blood flows through healthy hearts form optimal flow structures; they store flow kinetic energy (KE) that can be used for ejection. In contrast, in failing hearts, intracardiac flows become disorganized so that they may be energetically inefficient. However, it remained unknown whether left ventricular (LV) flow energetics prognosticates in heart failure. Methods This study included 61 patients with dilated cardiomyopathy (DCM). The temporal change in KE during early diastole (ED), atrial contraction (AC) and isovolumic contraction (IVC) was measured using Vector Flow Mapping particle tracking (Hitachi, figure top). LV inflow (total flow) were divided, based on whether they were ejected (direct flow, DF) or stayed in LV (retained flow, RF) in the following systole. KE of DF can be made use of for ejection, whereas KE of RF is supposed to be wasted. Diastolic function was graded, according to current EACVI/ASE guidelines. The patients were followed up for three years. Primary endpoint was hospitalization for worsening heart failure (WHF). Results 12 patients had hospitalizations for WHF in the follow-up period. KE of total flow did not show any significant difference through the cardiac cycle between patients with and without WHF. KE of DF was slightly, but not significantly, smaller (ED: p = 0.252, AC: p = 0.119, IVC: p = 0.122), and KE of RF was slightly, but not significantly, larger (ED: p = 0.971, AC: p = 0.085, IVC: p = 0.134) in patients with WHF than those without events. The ratio of DF and RF (DF/RF ratio) showed significant differences between these two groups, especially from AC through IVC (figure, bottom-left). Cox proportional hazard analyses demonstrated that DF/RF ratio during IVC showed a significant correlation with clinical outcomes (p = 0.033, hazard ratio = 0.067). It remained significant even after adjusted for diastolic function grade (p = 0.046, hazard ratio = 0.074). Kaplan-Meier analysis confirmed the above results (figure, bottom-right). Conclusion: Efficiency of KE recruitment for LV ejection during IVC is associated with clinical outcomes in DCM. Abstract P893 Figure. LISA

Daily remote monitoring of implantable cardioverter-defibrillators: insights from the pooled patient-level data from three randomized controlled trials (IN-TIME, ECOST, TRUST).

AimsRemote monitoring of implantable cardioverter-defibrillators may improve clinical outcome. A recent meta-analysis of three randomized controlled trials (TRUST, ECOST, IN-TIME) using a specific remote monitoring system with daily transmissions [Biotronik Home Monitoring (HM)] demonstrated improved survival. We performed a patient-level analysis to verify this result with appropriate time-to-event statistics and to investigate further clinical endpoints.Methods and resultsIndividual data of the TRUST, ECOST, and IN-TIME patients were pooled to calculate absolute risks of endpoints at 1-year follow-up for HM vs. conventional follow-up. All-cause mortality analysis involved all three trials (2405 patients). Other endpoints involved two trials, ECOST and IN-TIME (1078 patients), in which an independent blinded endpoint committee adjudicated the underlying causes of hospitalizations and deaths. The absolute risk of death at 1 year was reduced by 1.9% in the HM group (95% CI: 0.1–3.8%; P = 0.037), equivalent to a risk ratio of 0.62. Also the combined endpoint of all-cause mortality or hospitalization for worsening heart failure (WHF) was significantly reduced (by 5.6%; P = 0.007; risk ratio 0.64). The composite endpoint of all-cause mortality or cardiovascular (CV) hospitalization tended to be reduced by a similar degree (4.1%; P = 0.13; risk ratio 0.85) but without statistical significance.ConclusionIn a pooled analysis of the three trials, HM reduced all-cause mortality and the composite endpoint of all-cause mortality or WHF hospitalization. The similar magnitudes of absolute risk reductions for WHF and CV endpoints suggest that the benefit of HM is driven by the prevention of heart failure exacerbation.

No benefits of statins for sudden cardiac death prevention in patients with heart failure and reduced ejection fraction: A meta-analysis of randomized controlled trials.

Background and objectivesStatins showed mixed results in heart failure (HF) patients. The benefits in major HF outcomes, including all-cause mortality and sudden cardiac death (SCD), have always been discordant across systematic reviews and meta-analyses. We intended to systematically identify and appraise the available evidence that evaluated the effectiveness of statins in clinical outcomes for HF patients.DesignSystematic review and meta-analysisData sourcesWe searched, until April 28, 2016: Medline, Embase, ISI Web of Science and EBM reviews (Cochrane DSR, ACP journal club, DARE, CCTR, CMR, HTA, and NHSEED), checked clinicaltrials.gov for ongoing trials and manually searched references of included studies.Eligibility criteria for selecting studiesWe identified 24 randomized clinical trials that evaluated the efficacy of statins for HF patients. All randomized clinical trials were assessed for risk of bias and pooled together in a meta-analysis. Pre-specified outcomes were sudden cardiac death, all-cause mortality, and hospitalization for worsening heart failure.ResultsStatins did not reduce sudden cardiac death (SCD) events in HF patients [relative risk (RR) 0.92, 95% confidence interval (CI) 0.70 to 1.21], all-cause mortality [RR 0.88, 95% CI 0.75 to 1.02] but significantly reduced hospitalization for worsening heart failure (HWHF) although modestly [RR 0.79, 95% CI 0.66 to 0.94]. Nevertheless, estimated predictive intervals were insignificant in SCD, all-cause mortality and HWHF [RR, 0.54 to 1.63, 0.64 to 1.19, and 0.54 to 1.15], respectively. An important finding was the possible presence of publication bias, small-study effects and heterogeneity of the trials conducted in HF patients.ConclusionsStatins do not reduce sudden cardiac death, all-cause mortality, but may slightly decrease hospitalization for worsening heart failure in HF patients. The evaluation of the risk of biases suggested moderate quality of the published results. Until new evidence is available, this study supports the 2013 ACCF/AHA guidelines to not systematically prescribe statins in “only” HF patients, which should help avoid unnecessary polypharmacy.

Effects of Coping Skills Training on Quality of Life, Disease Biomarkers, and Clinical Outcomes in Patients With Heart Failure: A Randomized Clinical Trial.

Heart failure (HF) is a chronic disease that compromises patients' quality of life (QoL). Interventions designed to reduce distress and improve disease self-management are needed. We evaluated the efficacy of a telephone-based coping skills training (CST) intervention. This randomized clinical trial involved 180 HF outpatients with reduced ejection fraction. Participants ranged in age from 29 to 87 years (mean=58 years); 27% were women, and 47% were nonwhite. Participants were randomized to either a CST intervention or heart failure education, both delivered over 16 weeks. The primary outcomes were (1) postintervention effects on QoL and HF disease biomarkers (both with α=0.01), and (2) a composite measure of time to death or first hospitalization (with α=0.03) over a median follow-up period of 3 years. CST resulted in greater improvements in QoL compared with heart failure education (P<0.01), including the Kansas City Cardiomyopathy Questionnaire (P=0.009), depressive symptoms (P=0.027), and the 6-minute walk test (P=0.012). However, it did not differentially improve HF disease biomarkers or reduce risk of all-cause hospitalizations or death (hazard ratio=0.84 [95% confidence interval, 0.59-1.12]). Interestingly, exploratory analyses showed that participants randomized to CST experienced a reduction in the composite end point of worsening HF hospitalization or death during the 3-year follow-up period (hazard ratio=0.65 [95% confidence interval, 0.44-0.98]; P=0.040). CST improved QoL in patients with HF. Monitoring and improving QoL is emerging as an important aspect of the clinical management of HF that can reduce disease burden and may help improve clinical outcomes in this vulnerable patient population. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00873418.

Abstract 18395: Safety of Continuing Ivabradine Treatment During Hospitalization for Worsening of Heart Failure in the SHIFT Study

Background: Chronic medical treatment is usually adapted during hospitalizations for worsening heart failure (HWHF). Ivabradine, a heart rate (HR)-slowing agent that inhibits the funny current (If) in the sinus node, when added to standard of care reduced the relative risk of HWHF by 26% in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). Upon HWHF in SHIFT, ivabradine could be maintained even though patients were in acute/unstable HF. This post hoc exploratory analysis assessed the safety of continuing administration of ivabradine during HWHF in SHIFT. Methods: The safety of ivabradine within the 30 days following the first HWHF admission was assessed in patients receiving either ivabradine or placebo presenting with at least 1 adjudicated HWHF during the trial. The safety of ivabradine within the 30 days following the first HWHF admission in patients who continued study drug (CSD) versus those that discontinued study drug (DSD) during hospitalization within each treatment arm were compared. Results: Baseline characteristics of patients who were at least once HWHF were comparable between the ivabradine (n = 447) and placebo (n = 619) arms. During HWHF, study drug was continued in 70% of ivabradine- and 73% of placebo-treated patients. Within the 30 days following the first HWHF admission, serious adverse events were reported in 10.1% of ivabradine- (CSD: 11.1%, DSD: 7.6%) and 12.6% placebo-treated patients (CSD: 14.2%, DSD: 8.4%). Cardiovascular death was reported in 0.7% of ivabradine- (CSD: 0.6%, DSD: 0.8%) and 0.6% of placebo-treated patients (CSD: 0.9%, DSD: 0%). Conclusions: The safety profile of ivabradine in patients within 30 days following admission for HWHF was comparable to placebo, regardless of whether patients continued or discontinued study drug.

Risk stratification of patients with chronic heart failure using cardiac iodine-123 metaiodobenzylguanidine imaging: incremental prognostic value over right ventricular ejection fraction.

AimsRight ventricular (RV) systolic dysfunction has been shown to be an independent predictor of clinical outcome in patients with chronic heart failure (CHF), and cardiac metaiodobenzylguanidine (MIBG) imaging also provides prognostic information. We aimed to evaluate the long‐term predictive value of combining RV systolic dysfunction and abnormal findings of cardiac MIBG imaging on outcome in CHF patients.Methods and resultsWe enrolled 63 CHF outpatients with left ventricular ejection fraction (EF) <40% in a prospective cohort study. At entry, RVEF was measured by radionuclide angiography. Furthermore, cardiac MIBG imaging was performed, and the cardiac MIBG washout rate (WR) was calculated. Reduced RVEF was defined as ≤37%, and abnormal WR was defined as >27%. The study endpoint was unplanned hospitalization for worsening heart failure (WHF) and cardiac death. During a follow‐up period of 8.9 ± 4.3 years, 19 of 63 patients had unplanned hospitalization for WHF, and 19 of 63 patients had cardiac death. In multivariate analysis, both WR and RVEF were independent predictors of unplanned WHF hospitalization, while WR was also an independent predictor of cardiac death. A risk‐stratification model based on independent predictors of unplanned WHF hospitalization separated the patients into those with low (absence of the predictors), intermediate (one of the predictors), and high (two or more of the predictors) risk of unplanned WHF hospitalization (P < 0.0001) or cardiac death (P = 0.0113).ConclusionsCardiac MIBG imaging provides incremental value when it is used along with RV systolic dysfunction to predict clinical outcome in patients with CHF.

Inflammatory cytokines in chronic heart failure: interleukin‐8 is associated with adverse outcome. Results from CORONA

We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF). Serum levels of tumour necrosis factor-α (TNF-α), soluble TNF receptors type I and II (sTNF-RI and sTNF-RII), and the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were analysed in 1464 patients with chronic ischaemic systolic HF in the CORONA study, aged ≥ 60 years, in NYHA class II-IV, and related to the primary endpoint (n = 320), as well as any coronary event (n = 255), all-cause mortality (n = 329), cardiovascular (CV) mortality (n = 268), and the composite endpoint hospitalization from worsening heart failure (WHF) or CV mortality (n = 547). TNF-α, sTNF-RI, sTNF-RII, and IL-8, but not MCP-1, were independent predictors of all endpoints except the coronary endpoint in multivariable models including conventional clinical variables. After further adjustment for estimated glomerular filtration rate, the ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, only IL-8 remained a significant predictor of all endpoints (except the coronary endpoint), while sTNF- RI remained independently associated with CV mortality. Adding IL-8 to the full model led to a significant improvement in net reclassification for all-cause mortality and CV hospitalization, but only a borderline significant improvement for the primary endpoint, CV mortality, and the composite endpoint WHF hospitalization or CV mortality. Our study supports a relationship between IL-8 and outcomes in patients with chronic HF. However, the clinical usefulness of IL-8 as a biomarker in an unselected HF population is at present unclear.

Risk following hospitalization in stable chronic systolic heart failure

We explored the impact of being hospitalized due to worsening heart failure (WHF) or a myocardial infarction (MI) on subsequent mortality in a large contemporary data set of patients with stable chronic systolic heart failure (HF). A total of 6558 patients with stable systolic HF, 6505 with analysable data, with an EF of ≤35%, who were included in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT), were followed for a median of 22.9 months with respect to hospitalizations and vital status. Among the 1288 patients who had at least one hospitalization due to WHF or MI, 455 (35.3%) died during follow-up compared with 600 (11.5%) among patients not hospitalized for these reasons. The risk for death was highest in the early phase after hospitalization. The risk declined rapidly during the first month but remained 3.5-fold (95% confidence interval 2.3-5.1) increased at 18 months after a first WHF hospitalization and 8.8-fold (95% confidence interval 3.6-21.6) increased at 18 months after a first MI hospitalization. The present study confirms previous findings that in patients with stable chronic systolic HF, a hospitalization for WHF or MI is associated with substantially increased risk for subsequent death even with contemporary extensive background pharmacological therapy. The risk is most pronounced in the early phase of hospitalization but remains elevated even after 18 months. Preventing HF hospitalization appears as an important therapeutic objective in such patients, and a hospitalization for WHF or MI should lead to a careful therapeutic reassessment.

Abstract 17913: Linear Relationship Between Seattle Heart Failure Model Predicted Mortality and Hospitalizations in Patients with Chronic Heart Failure

Background Acute heart failure (HF) is a common and costly reason for hospitalization worldwide. We assessed the relationship between Seattle Heart Failure Model-D (SHFM-D) predicted mortality, total hospital days per year and discrete hospitalizations per year using data from the international Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy (ACCLAIM) trial. We hypothesized a linear relationship between SHFM-D predicted mortality and annual hospitalizations and days hospitalized. Methods and Results 2407 chronic HF subjects with a total of 1023 all-cause hospitalizations and 430 HF hospitalizations were grouped by SHFM-D score. There was a linear relationship between SHFM-D estimated mortality and all-cause and HF hospitalizations per year, and all-cause and HF hospital days per year. For each 10% increase in SHFM-D predicted mortality, there were approximately 8 additional all-cause hospital days per year and 5 additional HF hospital days per year (Figure 1), and 0.7 additional all-cause hospitalizations per year and 0.5 additional HF hospitalizations per year (Figure 2). The SHFM-D score also predicted the primary and secondary ACCLAIM endpoints: composite of death or cardiovascular hospitalization (AUC 0.63, 95% CI 0.61-0.66, p &lt; 0.001), death or worsening heart failure hospitalization (AUC 0.69, 95% CI 0.66-0.71, p &lt; 0.001), and all-cause death (AUC 0.73, 95% CI 0.69-76, p &lt; 0.001). Conclusions In the ACCLAIM cohort of patients with chronic systolic HF, there is a linear relationship between SHFM-D predicted mortality and annual hospitalizations and total days hospitalized.

Cardiac Resynchronization Therapy in Patients with Mild Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ObjectiveThis review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage.MethodsRandomized controlled trials of CRT in patients with New York Heart Association (NYHA) Class I or II heart failure were identified. The effects of CRT on worsening heart failure hospitalization, all-cause mortality, and overall adverse events were meta-analyzed, and the effects of CRT on left ventricular (LV) were systematically reviewed and meta-analyzed.ResultsEight studies were identified with a total of 4,302 patients. CRT was associated with a substantial improvement in LV end-systolic volume (WMD −39, 95%CI −41.56 to −36.45). CRT also had a marked effect in reducing new hospitalizations for worsening heart failure by 31% (RR 0.69, 95%CI 0.60 to 0.79). In addition, CRT significantly decreased all-cause mortality by 21% (RR 0.79, 95%CI 0.67 to 0.93). However, complications in patients with CRT increased by 74% (RR 1.74, 95%CI 1.44 to 2.11).ConclusionsThis meta-analysis suggests that CRT could improve the prognosis in patients with mild heart failure and ventricular dyssynchrony, but these improvements are accompanied by more adverse events. Since most patients in the included trials had received ICD therapy, our analysis suggests that CRT could offer an additional benefit.

Identifying patients at risk of death or hospitalisation due to worsening heart failure using decision tree analysis: Evidence from the Trans-European Network-Home-Care Management System (TEN-HMS) Study

ObjectivesTo stratify patients recently discharged from hospital with heart failure (HF) according to their risk of death and/or hospitalisation for worsening HF (WHF), to enable timely and appropriate monitoring and intervention. MethodsData from the TEN-HMS study were used in this analysis. Chi-square automatic interaction detector (CHAID) decision trees were constructed using a 10-fold cross-validation to predict events at 1-year and compared with logistic regression (LR) models using ROC curve analysis. Results284 patients were used for training and 160 patients available at 4-month for validation. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) was the strongest predictor of mortality identifying groups with high (>13,492pg/ml), medium (3127–13,492pg/ml) and low (≤3127pg/ml) risk, followed by MI, systolic blood pressure, age, heart rhythm, study randomisation group and serum sodium. NT-proBNP was also the strongest predictor for death or hospitalization for WHF identifying groups with high (>13,492pg/ml), medium (584–13,492pg/ml), and low (≤584pg/ml), followed by MI, creatinine, heart rhythm, potassium and urea. CHAID trees tended to perform better than LR-models (prediction of the composite outcome: ROC area with 95% CI, 0.797 (0.745–0.849) for CHAID and 0.738 (0.680–0.796) for LR-model; p=0.041; prediction of mortality: 0.892 (0.853–0.931) for CHAID and 0.858 (0.813–0.904) for LR; p=0.15). ConclusionsDecision trees are an alternative classification method used to differentiate risk in patients with HF. The resultant models are concise, free of subjective variables and understood easily by clinicians. Further exploration of their potential and validation in other data-sets is justified.

Predicting hospitalization due to worsening heart failure using daily weight measurement: analysis of the Trans‐European Network‐Home‐Care Management System (TEN‐HMS) study

We sought to test the utility of weight gain algorithms to predict episodes of worsening heart failure (WHF) using home-telemonitoring data collected as part of the TEN-HMS study. Simple rule-of-thumb (RoT) algorithms (i.e. 3 lbs in 1 day and 5 lbs in 3 days) and a moving average convergence divergence (MACD) algorithm were compared. WHF was defined as hospitalization for WHF or worsening of breathlessness or leg oedema. Of 168 patients, 45 were hospitalized with WHF and 76 were hospitalized for other reasons. On average, weight gain occurred in the 14 days prior to WHF hospitalizations but not in the 14 days prior to non-WHF hospitalizations [1.9 +/- 4.7 lbs (0.9 +/- 2.1 kg) vs. -0.4 +/- 2.5 lbs (-0.2 +/- 1.1 kg), P < 0.0001]. The true alerts rate was higher for the RoT algorithms compared with the MACD (58 and 65% vs. 20%). However, the RoT algorithms had much higher false alert rates (54 and 58% vs. 9%) rendering them of little practical use for predicting WHF events. A MACD algorithm is more specific but less sensitive than RoT when trying to predict episodes of WHF based on daily weight measurements. However, many episodes of WHF do not appear to be associated with weight gain and therefore telemonitoring of weight alone may not have great value for heart failure management.