Longer Duration Of Heart Failure Research Articles

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 eplerenone according to duration of heart failure in EMPHASIS-HF: It is never too late to start an MRA in HFrEF

Abstract Background In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF), the mineralocorticoid receptor antagonist (MRA) eplerenone reduced both the risk of death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF) and mild symptoms. However, many patients are still not prescribed an MRA and physicians may be reluctant to add another treatment in patients with longstanding HF who appear to be "stable" on their current therapy. Purpose As little is known about how the effect of MRA therapy varies by the duration of HF, we examined the efficacy of eplerenone according to time from HF diagnosis among patients in EMPHASIS-HF. The primary trial outcome was the composite of a first hospitalization for HF or cardiovascular death. Methods Three patient groups of similar size were created according to the duration of HF: &amp;lt;1 year, ≥1 to &amp;lt;5 years, and ≥5 years. Outcomes were analysed using Cox regression and the Kaplan-Meier estimate. Treatment effects were examined according to HF duration category and also using the duration of HF as a continuous variable. Results The number of patients in each group was: 975 (&amp;lt;1 year), 769 (1 - &amp;lt;5 years), and 988 (≥5 years), respectively. Patients with longer duration of HF were older and more frequently had an ischaemic aetiology of HF. Additionally, a longer duration of HF was associated with lower eGFR levels, wider QRS duration, and a higher proportion of atrial fibrillation at baseline. The rate of the primary outcome (per 100 person-year) increased with HF duration: 9.8 (95% CI: 8.4-11.4) for &amp;lt;1 year, 13.5 (11.6-15.7) for 1 - &amp;lt;5 years, and 17.6 (15.6-19.8) for ≥5 years. Similar trends were seen in all other outcomes (Figure 1). The hazard ratios for the effect of eplerenone compared to placebo on the primary outcome were 0.57 (95% CI: 0.42-0.79) for &amp;lt;1 year, 0.81 (0.60-1.10) for 1- &amp;lt;5 years, and 0.61 (0.48-0.78) for ≥5 years; P for interaction = 0.24. The benefits of eplerenone were also consistent across the duration of HF examined as a continuous variable (Figure 2). For the primary outcome, The number needed to treat (NNT) over the duration of the trial, for the primary outcome, was 14 for &amp;lt;1 year, 13 for 1 - &amp;lt;5 years and only 10 for ≥5 years duration. Conclusions Patients with a longer duration of HF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent in people with longer-standing HF and HF of shorter duration. These data suggest that it is never too late to start an MRA in patients with HFrEF. Figure 1. Outcomes according to heart failure duration category Abbreviations: CV cardiovascular; HF heart failure Figure 2. Treatment effects according to the duration of heart failure Abbreviations: CV cardiovascular; HF heart failureFigure 1Figure 2

Abstract 16662: Factors Associated With Repeated Emergency Department Visits Among Symptomatic Patients With Heart Failure

Heart failure (HF) is a prevalent cause of emergency department (ED) visits among adults. However, there is limited understanding of the characteristics of patients with HF who frequently utilize the ED for symptom management. Aim: To describe factors associated with ED revisits among symptomatic patients with chronic HF. Methods: We identified 1,472,083 adults (age ≥ 18 years) with HF who had no history of left ventricular assist device or heart transplantation between January 2010 and March 2020 from the TriNetX Research Network, which included 47 US healthcare organizations. In this retrospective observational study, 24,070 patients presenting with dyspnea and receiving intravenous (IV) Furosemide at the ED were followed up for 1 year from the index ED visit. ED revisits related to the treatment of dyspnea with IV diuretics were tracked. Factors associated with these ED revisits were identified using multivariate Cox regression analysis. Results: A total of 3,574 ED revisits were observed from 2,559 patients (10.6% of the sample, mean age 63 years, 51% men, 39% White, 62% Non-Hispanic). The ED revisit rates were 52, 96, 125, and 148 visits per 1,000 persons within 1, 3, 6, and 12 months, respectively. The median time to the first ED revisit for symptom management with IV diuretics was 65 days (range 2-364 days). In the Cox model, younger patients (&lt; 65 years) had a higher risk of ED revisits compared to older patients (HR 1.65, 95% CI 1.50-1.82, p&lt;0.001). Men had a higher risk of ED revisits compared to women (HR 1.12, 95% CI 1.02-1.23, p=0.02). Black patients had a higher risk of ED revisits compared to other races (HR 1.36, 95% CI 1.20-1.53, p&lt;0.001). Patients with HFrEF (e.g., ICD-10 I50.2) had a higher risk of ED revisits compared to those with congestive HF (e.g., ICD-10 I50 without HF type information) (HR 1.25, 95% CI 1.12-1.40, p &lt; 0.001). Patients diagnosed with HF more than 1 year prior to the index ED visit had a higher risk of ED revisits compared to those diagnosed within 1 year (HR 1.31, 95% CI 1.19-1.44, p &lt; 0.001). Conclusions: Younger age, male gender, Black race, HFrEF classification, and longer duration of HF were associated with ED revisits among symptomatic adults with HF. To reduce repeated ED visits, targeted interventions for high-risk patients are essential.

Importance of heart failure duration for development of pulmonary hypertension in advanced heart failure

Background and objectivesPulmonary vascular resistance (PVR) is critical when evaluating candidacy for advanced heart failure (HF) therapies, but risk factors for elevated PVR are not well studied. We hypothesized that HF duration would be associated with elevated PVR. MethodsDanish single-center registry of consecutive in- and outpatients undergoing right heart catheterization as part of advanced HF work up. The relation between HF duration and PVR was estimated by regression analysis. Finally, the relation between PVR and long-term mortality was assessed by Cox proportional hazards regression and Kaplan-Meier analyses. ResultsA total of 549 patients (77% men, median age 54 (43–61) years, median HF duration 1.6 years (0.1–7.1)) were included. Univariate linear regression displayed an association between longer HF duration and increasing PVR (p = 0.014). PVR > 3 WU was present in 92 patients (17%) who were older (median p < 0.001) and had longer HF duration (p = 0.03). HF duration (per 1 year increase) did not predict PVR > 3 WU after adjustment for covariables (OR 1.00; p = 0.99). During a mean follow-up time of 4.5 years, there were 240 (44%) deaths. Increasing PVR was associated with elevated all-cause mortality risk (adjusted HR 1.24; p < 0.001). PVR > 3 WU was associated with higher mortality (adjusted HR 1.49; p = 0.027). ConclusionLonger duration of HF was associated with higher PVR in patients with advanced HF, but this association disappeared in multivariate analyses. Longer HF duration per se likely does not cause elevated PVR and should not discourage evaluation for heart transplantation.

Duration of Heart Failure With Preserved Ejection Fraction and Outcomes With Sacubitril/Valsartan: Insights From the PARAGON-HF Trial

In this post hoc analysis of the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, we evaluated clinical outcomes and responses to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥ 45% at initial diagnosis. The primary outcome was a composite of total hospitalizations due to HF and cardiovascular deaths, analyzed by using a semiparametric proportional rates method, stratified by geographic region. Among 4784 (99.7%) randomized participants in the PARAGON-HF trial for whom baseline HF duration was captured, 1359 (28%) had durations of HF of < 6 months, 1295 (27%) of 6 months-2 years, and 2130 (45%) of > 2 years. Longer HF duration was associated with higher comorbidity burdens, worse health status and lower rates of prior hospitalization due to HF. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): < 6 months, 12.0 (95% CI, 10.4-14.0); 6 months-2 years, 12.2 (10.6-14.2); > 2 years, 15.8 (14.2-17.5). Relative treatment effects of sacubitril/valsartan vs valsartan were consistent, irrespective of baseline HF duration on the primary endpoint (Pinteraction = 0.112). Clinically meaningful (≥ 5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores were also similarly observed, irrespective of HF duration; (Pinteraction = 0.112). Adverse events were similar between treatment arms across HF duration categories. In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent, irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization.

Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction

In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF). To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population. In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022. Dapagliflozin, 10 mg, once daily or matching placebo. The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death. Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF. In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF. ClinicalTrials.gov Identifier: NCT03619213.

Frailty is associated with 90-day unplanned readmissions and death in patients with heart failure: A longitudinal study in China

BackgroundFrailty has been reported to be significantly associated with adverse health outcomes in people with heart failure (HF). ObjectivesTo explore the potential effects of frailty on unplanned readmissions and death in people with HF patients aged 18 years or older. Methods342 HF patients aged 18 years or older from the heart centers of two different tertiary care hospitals located in northwest of China were enrolled between July and December 2020. Frailty was assessed by the Tilburg Frailty Indicator. The patients were followed for unplanned readmissions, and all-cause mortality at 30, 60, as well as 90 days after discharge. Multivariate cox regression models were used to analyze the effects of frailty on 90-day unplanned readmission and death in the patients with HF. ResultsFrailty prevalence was 54.7% among 342 HF patients, with a mean age of 64.65 ± 11.90 years. It was found that compared to non-frailty HF patients, the frailty HF patients were older and displayed higher systolic blood pressure, longer duration of HF, more severe cognitive function, and more comorbidities (P < 0.05). On the contrary, the patients in the frail group had a higher incidence of unplanned readmission (73.1% vs. 26.9%, χ2 = 18.87, P < 0.01) and death (100% vs. 0%, χ2 = 6.94, P < 0.01) than those in the non-frail group. Multivariate cox regression analysis showed that frailty could serve as an independent risk factor for 90-day unplanned readmission (HR = 1.469, 95% CI 1.318–1.637, P < 0.01) and 90-day death (HR=2.270, 95% CI 1.091–4.726, P < 0.01) in the patients with HF. ConclusionFrailty can act as an independent predictor of unplanned readmission and death 90-day after discharge in HF patients aged 18 years or older.

Atrial fibrillation and mortality in outpatients with heart failure in Tanzania: a prospective cohort study

ObjectiveIn recent years, the prevalence and mortality of heart failure (HF) and other associated cardiovascular diseases have doubled in sub-Saharan Africa (SSA). Studies in high-income countries indicate that HF with...

Re-worsening left ventricular ejection fraction after response to cardiac resynchronization therapy

BackgroundAlthough cardiac resynchronization therapy (CRT) provided functional and clinical improvement in patients with heart failure (HF) and electrical intraventricular conduction disturbances, some patients had re-worsening left ventricular (LV) function after a favorable CRT response. We analyzed the clinical variables and cardiac outcomes associated with this re-worsening LV function after CRT. MethodsIn this study, 71 patients with CRT response who received CRT between 2006 and 2017 were included. CRT response was defined as a “≥ 10% improvement in LV ejection fraction (LVEF) on follow-up.” Patients were classified into two groups: (i) persistent: (n = 48, 68%), defined as those with a CRT response and (ii) re-worsening: (n = 23, 32%), consisting of those who fell out of the definition of a CRT response after an initial CRT response. ResultsHalf of the patients in the re-worsening group failed to maintain a CRT response from two years upwards. A longer duration from HF diagnosis to CRT implantation, nonspecific intraventricular conduction delay (NIVCD) on electrocardiogram at CRT implantation, and a lower increased LVEF at initial CRT response were independent predictors for the re-worsening group. Patients in the re-worsening group had a higher incidence rate for HF hospitalization and cardiac deaths, compared with those in the persistent group. ConclusionOne-third of CRT responders experienced re-worsening LVEF, which was associated with poor outcomes. CRT responders with NIVCD, longer HF duration, and a lower increased LVEF at initial CRT response should be monitored with caution.

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial

Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite usage of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group. Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association class [NYHA] II-IV) and ejection fraction <45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical endpoints, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, non-linearities, and interactions with treatment. Optimism-corrected c-indices were calculated using 200 bootstrap samples. During a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 (38.5%) patients. Independent predictors of increased risk for the primary endpoint included HF characteristics (longer HF duration and worse NYHA class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death. Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk HF patients who were receiving excellent guideline-based clinical care. Clinicaltrials.gov identifier, NCT02861534. Patients with heart failure may benefit from tools that help clinicians better understand patient's risk for future events like hospitalization. Relatively few risk models have been created after worsening of heart failure in a contemporary cohort. We provide insights on risk factors for clinical events from a recent large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.

Heart failure is independently associated with white matter lesions: insights from the population-based LIFE-Adult Study.

AimsWhite matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML.Methods and resultsThe LIFE‐Adult Study is a population‐based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0–1, and 334 (13.4%) had Fazekas score of 2–3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54–62). Age, troponin T, NT‐proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2–3) with HF was 2.8 (95% CI 1.2–6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend).ConclusionsIn addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML.

Association of heart failure duration with clinical outcomes after transcatheter mitral valve repair for functional mitral regurgitation.

Little is known about the association of heart failure (HF) chronicity with clinical outcomes after transcatheter mitral valve repair (TMVR) for functional mitral regurgitation (MR). From January 2011 to March 2019, consecutive patients with functional MR who underwent a MitraClip procedure were analyzed. The patients were divided into two groups according to HF duration-those with duration ≤18 months and those with >18 months. The primary outcome measure was a composite of all-cause mortality and re-HF rehospitalization within 1 year after the procedure. These outcomes were also assessed separately. A Cox proportional hazard model was conducted for investigating the association of HF duration with the primary outcome. A total of 208 patients were analyzed. Patients with HF duration >18 months had a higher rate of the primary outcome compared to those with HF duration ≤18 months (38.1 vs. 19.0%, log-rank p=.003). A longer duration of HF was associated with an increased risk of the primary outcomes (adjusted-HR of >18 months, 2.12 95% CI, 1.14-4.19; p=.03; adjusted-HR (hazard ratios) for 1 year increase, 1.05; 95% CI, 1.02-1.09; p=.004). The association of HF duration with the primary outcomes showed a steep rise during the first 2 years of HF duration and progressive increase after 5 years. A longer HF duration before TMVR was associated with an increased risk of all-cause mortality or HF rehospitalization. HF duration can be used for the risk stratification marker in patients undergoing TMVR for functional MR.

Abstract 16374: Effect of Dapagliflozin According to Duration of Heart Failure: An Analysis of the DAPA-HF Trial

Introduction: The relationship between duration of heart failure (HF), patient characteristics, outcomes, and the effect of treatment is largely unknown. We investigated these questions in DAPA-HF. Hypothesis: We hypothesized that longer HF duration is associated with worse outcomes and that, compared with placebo, the benefit of the SGLT2 inhibitor, dapagliflozin, is consistent, irrespective of HF duration, in patients with HF and reduced ejection fraction (HFrEF). Methods: HF duration was categorised as 0-1, &gt;1-2, &gt;2-5 and &gt;5 years. Outcomes were adjusted for prognostic variables and analysed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect (dapagliflozin versus placebo) was examined within each duration category and by duration threshold. Results: The number patients in each category was: 1098 (0-1 year), 686 (&gt;1-2 years), 1105 (&gt;2-5 years) and 1855 (&gt;5 years). Patients with longer-duration HF were older and more comorbid with worse quality of life. The primary outcome rate (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for the 0-1-year group, 10.6 (8.7-12.9) for &gt;1-2 years, 15.5 (13.6-17.7) for &gt;2-5 years and 15.9 (14.5-17.6) for &gt;5 years. The adjusted hazard ratio was 0.98 (95% CI 0.75-1.27), 1.52 (1.22-1.89) and 1.60 (1.31-1.96) respectively, for &gt;1-2, &gt;2-5 and &gt;5 years compared with 0-1 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration for all outcomes and on threshold analysis (Figure). Conclusion: Patients with longer-duration HF had higher rates of worsening HF and death. The benefit of dapagliflozin was consistent irrespective of HF duration. Starting dapagliflozin has substantial benefits, even in patients with longstanding HFrEF.

P4715Association of heart failure duration with clinical prognosis after transcatheter mitral valve repair

Abstract Background/Introduction Transcatheter mitral valve repair (TMVR) in patients with heart failure (HF) and severe mitral regurgitation (MR) entails better clinical and symptomatic status. While emerging evidence indicate that HF duration is linked to adverse outcomes in patients with HF, it is not known whether the HF duration before TMVR has an effect on adverse outcomes. Purpose We aimed to assess the association between duration of HF before TMVR and clinical prognosis after the procedure. Methods We retrospectively enrolled a total of 345 patients who underwent TMVR procedure with MitraClip or Cardioband system for the treatment of symptomatic MR after guideline recommended therapy. The patients were divided into 2 groups according to the duration of HF (&gt;18 months:, n=161, ≤18 months: shorter HF group, n=184). Cox proportional hazards analysis was performed to assess the association between duration and two-year composite endpoint (all-cause mortality, unexpected hospitalization due to HF, and repeat mitral valve therapy). Results Patients with longer duration of HF were more likely to be male, had greater incidence of coronary artery disease (77.0% vs. 51.6%, p&lt;0.001), had received more frequently implantable cardioverter defibrillator or cardiac resynchronization therapy (41.0% vs. 10.3%, p&lt;0.001), and had more decreased left ventricular ejection fraction (41.1±14.5% vs. 49.3±16.0%, p&lt;0.001) compared to patients with shorter duration of HF. Two-year event-free survival rate was significantly lower in patients with longer duration of HF (66.3% vs. 83.8%, Log-rank p=0.01) compared to whose with shorter duration of HF. Similar trends were observed for all-cause mortality (84.8% vs. 95.9%, p=0.06) and repeat mitral valve therapy (93.4% vs. 100%, p=0.02). In the Cox proportional hazard analysis, longer duration of HF was independently associated with increased risk of adverse outcomes (Hazard ratio, 2.26; 95% confidence interval, 1.11–4.62; p=0.02) compared with shorter duration of HF. Conclusion Patients with the longer duration of HF before TMVR is independently associated with increased risk of adverse outcomes after the procedure. It is, however, accompanied by higher prevalence of cardiac co-morbidities in these patients. Our findings suggest that a longer duration of HF is a risk indicator and should be considered into in future clinical trials of TMVR.

P4533Duration of heart failure and effect of defibrillator implantation in patients with non-ischemic systolic heart failure

Abstract Introduction Patients with non-ischemic systolic heart failure have increased risk of sudden cardiac death (SCD) and death from progressive pump failure. Whether the risk of SCD changes over time is unknown. We seek to investigate the relationship between duration of heart failure, mode of death, and effect of implantable cardioverter defibrillator (ICD) implantation. Methods We examined the risk of all-cause death and SCD according to the duration of heart failure among patients with non-ischemic systolic heart failure enrolled in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial. Patients were divided according to quartiles of heart failure duration (Q1 ≤8 months, Q2 9 ≤18 months, Q3 19 ≤65 months, Q4 ≥66 months). Results A total number of 1116 patients were included. Patients with the longest duration of heart failure were older, more often men, had more comorbidity, and more often received cardiac resynchronizing therapy device. Doubling of heart failure duration was an independent predictor of both all-cause mortality (HR 1.26 95% CI 1.17–1.37, p&lt;0.0001), and SCD (HR 1.29 95% CI 1.11–1.49, p=0.0009). The proportion of deaths caused by SCD was not different between heart failure quartiles (p=0.91), and the effect of ICD implantation on all-cause mortality was not modified by the duration of heart failure (p=0.59). Duration of heart failure and death Conclusions Duration of heart failure predicted both all-cause mortality and risk of SCD independently of other risk indicators. However, the proportion of death caused by SCD did not change with longer duration of heart failure and the effect of ICD was not modified by the duration of heart failure. Acknowledgement/Funding The work was sponsored by The Danish Heart Foundation (Hjerteforeningen) and the Lundbeck Foundation (Lundbeckfonden). The DANISH trial was supported

P3544Role of cardiovascular comorbidities in heart failure across the ejection fraction spectrum

Abstract Background Comorbidities are associated with heart failure (HF) development, severity and outcomes, but may play different roles in HF with preserved (HFpEF) vs. mid-range (HFmrEF) vs. reduced ejection fraction (HFrEF). A detailed characterization of HF patients according to EF and comorbidities may improve prognostication and facilitate trial design. Purpose To investigate characteristics and outcomes in a large and unselected cohort of HF patients according to EF strata and presence/absence of concomitant type 2 diabetes (T2DM), atrial fibrillation (AF) and chronic kidney disease (CKD). Methods Patients enrolled in the Swedish HF registry between 2000–2012 were considered. Kaplan Meier curves and multivariable Cox regression models were fitted to assess risk and predictors of outcomes (HF and all-cause hospitalization; composite of cardiovascular (CV) death and HF hospitalization). Results Of 42,583 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 49% CKD defined as eGFR&amp;lt;60 ml/min/1.73m2, and 56% AF. T2DM, AF and CKD coexisted in 8% of the population with similar distribution across all EF strata. AF and CKD were the most likely to coexist. Prevalence of AF and/or CKD was highest in HFpEF and lowest in HFrEF, whereas prevalence of T2DM was similar across the EF spectrum (Figure). Compared to patients without T2DM and/or AF and/or CKD, those with any of them were more likely to suffer from other comorbidities (i.e. hypertension, anemia, COPD), to be inpatients, have more severe HF (higher NYHA class, NT-proBNP levels and use of diuretics, longer HF duration) but less likely to be followed-up in specialty vs. primary care. Concomitant history of ischemic heart disease was more likely in patients with vs. without CKD and/or T2DM but less likely in those with vs without AF. Patients with vs. without T2DM and/or CKD and/or AF had worse prognosis. In particular, risk of HF hospitalization and composite of HF hospitalization/CV death was highest in patients with HFrEF and concomitant comorbidities, whereas the risk of all-cause hospitalization was highest in those with HFpEF or HFmrEF and concomitant comorbidities. Prognostic predictors of CV death/HF hospitalization were consistent in patients with T2DM, CKD or AF, regardless of EF (e.g. male sex, older age, lower EF category, more severe HF, ischemic heart disease, anemia, COPD). Comorbidities burden Conclusion HF patients show a high burden of concomitant diseases, specifically T2DM, CKD and AF. CKD and AF are more prevalent in HFpEF vs. HFmrEF vs. HFrEF, whereas T2DM prevalence is consistent across the EF spectrum. Presence of comorbidities identifies patients with more severe HF regardless of EF category. Presence of comorbidities may identify patients at higher risk of CV outcomes in HFrEF and those at higher risk of non-CV events in HFpEF. Acknowledgement/Funding This study has been supported by funding from Boehringer Ingelheim

Duration of Heart Failure and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

Patients with nonischemic systolic heart failure (HF) have increased risk of sudden cardiac death (SCD) and death from progressive pump failure. Whether the risk of SCD changes over time is unknown. We seek here to investigate the relation between duration of HF, mode of death, and effect of implantable cardioverter-defibrillator implantation. We examined the risk of all-cause death and SCD according to the duration of HF among patients with nonischemic systolic HF enrolled in the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality). In all, 1116 patients were included. Patients were divided according to quartiles of HF duration (≤8, 9≤18, 19≤65, and ≥66 months). Patients with the longest duration of HF were older, more often men, had more comorbidity, and more often received a cardiac resynchronization therapy device. Doubling of HF duration was an independent predictor of both all-cause mortality (hazard ratio [HR], 1.27; 95% CI, 1.17-1.38; P<0.0001), and SCD (HR, 1.29; 95% CI, 1.11-1.50; P=0.0007). The proportion of deaths caused by SCD was not different between HF quartiles (P=0.91), and the effect of implantable cardioverter-defibrillator implantation on all-cause mortality was not modified by the duration of HF (P=0.59). Duration of HF predicted both all-cause mortality and risk of SCD independently of other risk indicators. However, the proportion of death caused by SCD did not change with longer duration of HF, and the effect of implantable cardioverter-defibrillator was not modified by the duration of HF. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Association of heart failure duration with clinical prognosis in advanced heart failure.

Little is known about the prognostic impact of heart failure (HF) duration in patients with advanced HF. A total of 109 consecutive patients with advanced HF referred to the institutional heart transplant program between July 2014 and December 2017 were prospectively enrolled. The patients were divided into two groups according to the HF duration using a pre-specified cutoff (> 18months, n = 38; ≤ 18months, n = 71). The Cox proportional hazards model was generated to investigate the association between the HF duration and a 1-year composite endpoint (all-cause mortality, left ventricular assist device implantation, and hospitalization due to HF). Patients with a longer HF duration were older and had significantly lower blood pressure, and greater left ventricular volume compared with those with a shorter HF duration. The 1-year event-free survival rate was significantly lower in patients with a longer HF duration (49.1% vs. 80.0%, log-rank p < 0.001). After adjustment, a longer HF duration was independently associated with an increased risk for the composite endpoint (hazard ratio, 2.44; 95% confidence interval, 1.03-5.76; p = 0.04). Additionally, longer HF duration was independently associated with an increased wall motion score index and a decreased heart-to-mediastinum ratio of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy (all associations, p < 0.05). A longer HF duration is associated with an increased risk of adverse outcomes as well as more severe myocardial damage among patients with advanced HF.

Duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with ivabradine: findings from SHIFT

In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration. Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.

323 - Predictors and Outcomes of Improved Left Ventricular Ejection Fraction in Outpatients with Heart Failure and Reduced Ejection Fraction

Introduction: Limited data are available on the epidemiology and predictors of improvement or recovery of left ventricular ejection fraction (LVEF) in outpatients with heart failure (HF) and reduced (≤40%) LVEF (HFrEF). Also, data on the impact of LVEF improvement on outcomes in these patients are scarce. Hypothesis: We hypothesized that (1) clinical characteristics of outpatients with HFrEF can predict improvement of LVEF (to >40%) by 1 year and (2) LVEF improvement (to >40%) leads to lower risk for subsequent events (death and HF admissions). Methods: We evaluated 805 patients with HFrEF who received outpatient care from 01/01/12 to 03/31/12 (inception period) and extracted data on serial echocardiographic assessments, interim advanced HF therapies, and outcomes. To assess impact of LVEF trajectory on outcomes, we performed a landmark analysis at 1 year follow-up. Results: Among 724 patients who were alive at 1 year and had not received advanced HF therapies in the interim, 380 (52.5%) had repeat echocardiograms. Of those, 57/380 (15.0%) had improved LVEF to >40% (median change, +18%; 25th to 75th percentile, +10% to +25%), whereas 323 did not improve (0%; -5% to +5%). Table 1 presents the baseline characteristics according to 1-year LVEF change. Baseline LVEF ≥30% (odds ratio [OR] 5.06; 95%CI 2.62–9.77; P < .001), nonischemic HF (OR 2.11; 95%CI 1.11–4.02; P=.023), and absence of implantable cardioverter defibrillator (OR 3.37; 95%CI 1.36–8.35; P=.009) predicted LVEF improvement to >40%. In a subset of 272 patients with data on HF duration, improvement was less likely with longer HF duration (OR per year 0.83; 95%CI 0.72–0.94; P=.005). In a landmark analysis at 1 year, 5/57 patients with improved LVEF died in the next 2 years vs. 55/323 among non-improvers (2-year mortality: 10.1% vs. 17.1%, log-rank P=.13). Improvers had significantly lower rates of combined death or HF admission vs. non-improvers (Fig. 1), hazard ratio 0.37 (95%CI 0.20–0.70; P=.002) in adjusted models. Conclusions:In our chronic HFrEF cohort, 15% of patients improved their LVEF within 1 year. These patients experienced lower rates of combined mortality and HF admission in the next 2 years.Table 1Baseline characteristics according to LVEF status at 1 year (N = 380).Fig. 1Death of admission for HF according to LVEF improvement by 1 year.View Large Image Figure ViewerDownload Hi-res image Download (PPT)