Higher Risk Of Heart Failure Hospitalization Research Articles

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction

BackgroundInflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. ObjectivesThis study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. MethodsOf 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. ResultsFemale sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). ConclusionsPatients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Prognostic significance of growth differentiation factor-15 across age in chronic heart failure.

Growth differentiation factor-15 (GDF15), a cytokine in the transforming growth factor family, is up-regulated in stress and inflammatory conditions and is elevated in patients with heart failure (HF). However, the age-specific attributes and prognostic significance of GDF15 across age remain unknown in chronic HF (CHF). Serum levels of GDF15 were examinedin 942 hypertensive patients (median 68years) with CHF from the SUPPORT trial across the four age groups [under 50 (n=73), 51-59 (n=158), 60-69 (n=296), and 70-79years (n=415)] and in the continuous spectrum. Clinical correlates of GDF15 were explored using the classic stepwise and LASSO (least absolute shrinkage and selection operator) regression approaches. Interaction terms with age were tested in the LASSO regression approach. The associations with the composite outcome of HF hospitalization or all-cause death were investigated across ages. Median GDF15 levels (pg/mL) increased along with aging, from 691 in under 50years to 855 in 51-59years, 1114 in 60-69years, and 1516 in 70-79years (trend P<0.001). Age, sex, systolic blood pressure, history of diabetes, ischaemic heart disease, left ventricular (LV) end-systolic dimension, LV ejection fraction, estimated glomerular filtration rate, haemoglobin, N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin, C-reactive protein, and the use of angiotensin-converting enzyme inhibitors, diuretics, and statins were mutually selected as clinical covariates of GDF15. The LASSO regression analysis identified significant interactions between age and the history of diabetes and NT-proBNP, with particularly robust associations in patients aged between 60 and 70years. During the mean follow-up of 8.6years, 474 composite endpoints of HF hospitalization or death occurred. GDF15 was associated with a higher risk of HF hospitalization or all-cause death [adjusted hazard ratio 1.84 (95% confidence interval 1.45-2.33)], with a particularly heightened risk in patients aged around 70years (Pinteraction=0.0008). The model with GDF15 on top of other established risk factors yielded marginally higher C-statistics compared with the model without GDF15 (0.803 and 0.796, P=0.045). The additive value of GDF15 on top of other established risk factors appeared similar across ages. A universal cut-off value of 1400pg/mL performed well in discriminating between those with and without HF hospitalization or death. Some clinical correlates of GDF15 have an interaction with age. GDF15 is an important determinant of cardiovascular endpoints, particularly in patients aged around 70years. The additive value of GDF15 appeared consistent across ages, suggesting the use of a universal cut-off value.

Atrial fibrillation and risk of adverse outcomes in heart failure with reduced, mildly reduced, and preserved ejection fraction: A systematic review and meta-analysis.

Heart failure (HF) and atrial fibrillation (AF) frequently co-exist. Contemporary classification of HF categorizes it into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Aggregate data comparing the risk profile of AF between these three HF categories are lacking. We conducted a systematic review and meta-analysis aimed at determining any significant differences in AF-associated all-cause mortality, HF hospitalizations, cardiovascular mortality (CV), and stroke between HFrEF, HFmrEF, and HFpEF. A systematic search of PubMed, EMBASE, and Cochrane Library databases until February 28, 2023. Data were combined using DerSimonian-Laird random effects model. A total of 22 studies comprising 248 323 patients were retained: HFrEF 123 331 (49.7%), HFmrEF 40 995 (16.5%), and HFpEF 83 997 (33.8%). Pooled baseline AF prevalence was 36% total population, 30% HFrEF, 36% HFmrEF, and 42% HFpEF. AF was associated with a higher risk of all-cause mortality in the total population with pooled hazard ratio (HR) = 1.13 (95% confidence interval [CI] = 1.07-1.21), HFmrEF (HR = 1.25, 95% CI = 1.05-1.50) and HFpEF (HR = 1.16, 95% CI = 1.09-1.24), but not HFrEF (HR = 1.03, 95% CI = 0.93-1.14). AF was associated with a higher risk of HF hospitalizations in the total population (HR = 1.29, 95% CI = 1.14-1.46), HFmrEF (HR = 1.64, 95% CI = 1.20-2.24), and HFpEF (HR = 1.46, 95% CI = 1.17-1.83), but not HFrEF (HR = 1.01, 95% CI = 0.87-1.18). AF was only associated with CV in the HFpEF subcategory but was associated with stroke in all three HF subtypes. AF appears to be associated with a higher risk of all-cause mortality and HF hospitalization in HFmrEF and HFpEF. With these findings, the paucity of data and treatment guidelines on AF in the HFmrEF subgroup becomes even more significant and warrant further investigations.

Biatrial myopathy in heart failure with preserved ejection fraction.

Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.

The prognostic association of atrial fibrillation on heart failure hospitalizations after acute myocardial infarction

Abstract Aims The association of atrial fibrillation (AF) with heart failure (HF) specific hospitalizations after acute myocardial infarction (AMI) is unclear. We aim to study the association of AF and 6-month HF hospitalization after an AMI in a large American cohort. Methods and Results Adult survivors of a AMI hospitalization without cardiogenic shock were identified from the 2019 US Nationwide Readmissions Database. The unadjusted association of AF (pre-existing and denovo) with baseline characteristics and primary outcome of rate of 6-month HF admission, and secondary outcomes of fatal HF admission, composite of HF peri-AMI or a 6-month HF admission, and a composite of 6-month HF or death during a non−HF-related admission was evaluated using chi square tests or t-tests, and independent associations of AF on outcomes were evaluated using multivariable logistic regression. Cox proportional hazards models were used to identify the association of AF on cumulative incidence risk on HF readmission. Of 262,390 AMI survivors, AF was present in 18.0%. By 6-months, HF hospitalization occurred in 5.4% of all patients. AF was associated with a higher adjusted risk for 6-month HF admission (OR 1.42, 95% CI: 1.34-1.50). In the adjusted time-to-event analysis, AF was associated with a higher risk for 6-month HF readmission (HR 1.39, 95% CI 1.31-1.46, P&amp;lt;0.001). AF was associated with a higher risk for fatal HF and the composite outcomes. Conclusions AF was present in 1 in 6 AMI survivors without cardiogenic shock and AF was associated with a higher risk of HF hospitalization in the subsequent 6-month period.Cumulative Incidence CurvesOutcomes Table

Abstract 11936: Cardiorenal Prognostic Significance of IGFBP-7 Concentrations in Chronic Heart Failure: Findings From EMPEROR-Pooled

Introduction: Insulin-like growth factor binding protein-7 (IGFBP-7) is a biomarker of tissue senescence with a role in heart failure (HF) pathophysiology. We examined the association of IGFBP-7 with risk of HF hospitalization or cardiovascular (CV) death and progression of renal disease in the EMPEROR-Reduced and EMPEROR-Preserved Trials. Methods: IGFBP-7 was measured in serum samples in the placebo and empaglifozin arms at baseline (N= 561, 564), 12 weeks (N=558, 557) and 52 weeks (N=355, 358). IGFBP-7 was measured using Roche Cobas Elecsys assay within the Biomarker Research Agreement of Boehringer Ingelheim, the sponsor of the EMPEROR trials and Roche Diagnostics International Ltd. Association between IGFBP-7 and risk of HF hospitalization or CV death, estimated glomerular filtration rate (eGFR) slope, and renal composite outcome of sustained eGFR reduction ≥40% or end-stage renal disease were evaluated using multivariable modeling. Results: Study participants with IGFBP-7 levels in the third tertile had a higher risk clinical profile compared to those with lower values. Empagliflozin was not meaningfully associated with change in IGFBP7 at 12 or 52 weeks. In Cox proportional hazards models adjusted for clinical variables, N-terminal pro-B type natriuretic peptide and high-sensitivity cardiac troponin T, baseline IGFBP-7 values above the second tertile predicted a higher risk of HF hospitalization or CV death (HR: 2.00 95% CI 1.28-3.10, p=0.002), higher rate of eGFR decline (β estimate: -2.45, 95% CI: -3.40 - -1.50, p for trend =0.005) and higher risk of renal composite endpoint (HR: 4.66, 95% CI: 1.61-13.53, p=0.005). Empagliflozin reduced risk for CV death/HF hospitalization irrespective of baseline IGFBP-7 (p-trend across IGFBP-7 tertiles=0.26). Concentrations of IGFBP-7 were moderately correlated with other prognostic HF biomarkers of tissue remodeling including fatty acid binding protein-3, growth differentiation factor-15, and angiopoietin-2. Conclusions: IGBP-7 was correlated with worse clinical presentation and associated with adverse cardiovascular outcomes even in models adjusted for conventional biomarkers. Empagliflozin did not significantly affect IGFBP-7 levels over time.

Utility of left ventricular ejection fraction in atrial fibrillation patients without pre-existing heart failure.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus has been placed on the prevention of HF in patients with AF. Left ventricular ejection fraction (LVEF) is an established echocardiographic parameter in HF patients. We sought to investigate the association of LVEF with HF events in AF patients without pre-existing HF. The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. In this analysis, we excluded patients with pre-existing HF (defined as having one of the following: prior HF hospitalization, New York Heart Association class≥2 in association with heart disease, or LVEF<40%). Among 3233 AF patients without pre-existing HF, we investigated 2459 patients with the data of LVEF at enrolment. We divided the patients into three groups stratified by LVEF [mildly reduced LVEF (40-49%), below normal LVEF (50-59%), and normal LVEF (≥60%)] and compared the backgrounds and incidence of HF hospitalization between the groups. Of 2459 patients [mean age: 72.4±10.5years, female: 917 (37%), paroxysmal AF: 1405 (57%), and mean CHA2 DS2 -VASc score: 3.0±1.6], the mean LVEF was 66±8% [mildly reduced LVEF: 114 patients (5%), below normal LVEF: 300 patients (12%), and normal LVEF: 2045 patients (83%)]. Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P<0.01), but age and CHA2 DS2 -VASc score were comparable between the three groups (both P>0.05). During the median follow-up period of 6.0years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF [mildly reduced LVEF (40-49%): hazard ratio=2.98, 95% confidence interval=1.99-4.45 and below normal LVEF (50-59%): hazard ratio=2.01, 95% confidence interval=1.44-2.82, compared with normal LVEF (≥60%)] after adjustment by age, sex, type of AF, and CHA2 DS2 -VASc score. LVEF<60% was significantly associated with the higher risk of HF hospitalization across all major subgroups without significant interaction (P for interaction; all P>0.05). LVEF had an independent and incremental prognostic value for HF hospitalization in addition to natriuretic peptide levels in AF patients without pre-existing HF. Lower LVEF was significantly associated with the higher incidence of HF hospitalization in AF patients without pre-existing HF, leading to the future risk stratification for and prevention of incident HF in AF patients.

Beta-Blocker Use and Heart Failure Outcomes in Mildly Reduced and Preserved Ejection Fraction

BackgroundAlthough studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and suggest potential negative effects in heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to examine the association of beta-blockers with heart failure (HF) hospitalization and death in patients with HF and EF ≥40% MethodsBeta-blocker use was assessed at first encounter in outpatients ≥65 years of age with HFmrEF and HFpEF in the U.S. PINNACLE Registry (2013-2017). The associations of beta-blockers with HF hospitalization, death, and the composite of HF hospitalization/death were assessed using propensity-score adjusted multivariable Cox regression models, including interactions of EF × beta-blocker use. ResultsAmong 435,897 patients with HF and EF ≥40% (HFmrEF, n = 75,674; HFpEF = 360,223), 289,377 (66.4%) were using a beta-blocker at first encounter; more commonly in patients with HFmrEF vs HFpEF (77.7% vs 64.0%; P < 0.001). There were significant interactions between EF × beta-blocker use for HF hospitalization, death, and composite of HF hospitalization/death (P < 0.001 for all), with higher risk with beta-blocker use as EF increased. Beta-blockers were associated with decreased risk of HF hospitalization and death in patients with HFmrEF but a lack of survival benefit and a higher risk of HF hospitalization in patients with HFpEF, particularly when EF was >60%. ConclusionsIn a large, real-world, propensity score-adjusted cohort of older outpatients with HF and EF ≥40%, beta-blocker use was associated with a higher risk of HF hospitalization as EF increased, with potential benefit in patients with HFmrEF and potential risk in patients with higher EF (particularly >60%). Further studies are needed to understand the appropriateness of beta-blocker use in patients with HFpEF in the absence of compelling indications.

Anthropometric measures and adverse outcomes in heart failure with reduced ejection fraction: revisiting the obesity paradox.

Although body mass index (BMI) is the most commonly used anthropometric measure, newer indices such as the waist-to-height ratio, better reflect the location and amount of ectopic fat, as well as the weight of the skeleton, and may be more useful. The prognostic value of several newer anthropometric indices was compared with that of BMI in patients with heart failure (HF) and reduced ejection fraction (HFrEF) enrolled in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure. The primary outcome was HF hospitalization or cardiovascular death. The association between anthropometric indices and outcomes were comprehensively adjusted for other prognostic variables, including natriuretic peptides. An 'obesity-survival paradox' related to lower mortality risk in those with BMI ≥25 kg/m2 (compared with normal weight) was identified but this was eliminated by adjustment for other prognostic variables. This paradox was less evident for waist-to-height ratio (as an exemplar of indices not incorporating weight) and eliminated by adjustment: the adjusted hazard ratio (aHR) for all-cause mortality, for quintile 5 vs. quintile 1, was 1.10 [95% confidence interval (CI) 0.87-1.39]. However, both BMI and waist-to-height ratio showed that greater adiposity was associated with a higher risk of the primary outcome and HF hospitalization; this was more evident for waist-to-height ratio and persisted after adjustment e.g. the aHR for HF hospitalization for quintile 5 vs. quintile 1 of waist-to-height ratio was 1.39 (95% CI 1.06-1.81). In patients with HFrEF, alternative anthropometric measurements showed no evidence for an 'obesity-survival paradox'. Newer indices that do not incorporate weight showed that greater adiposity was clearly associated with a higher risk of HF hospitalization.

Timing of cardiac resynchronization therapy implantation.

The optimum timing of cardiac resynchronization therapy (CRT) implantation is unknown. We explored long-term outcomes after CRT in relation to the time interval from a first heart failure hospitalization (HFH) to device implantation. A database covering the population of England (56.3 million in 2019) was used to quantify clinical outcomes after CRT implantation in relation to first HFHs. From 2010 to 2019, 64 968 patients [age: 71.4 ± 11.7 years; 48 606 (74.8%) male] underwent CRT implantation, 57% in the absence of a previous HFH, 12.9% during the first HFH, and 30.1% after ≥1 HFH. Over 4.54 (2.80-6.71) years [median (interquartile range); 272 989 person-years], the time in years from the first HFH to CRT implantation was associated with a higher risk of total mortality [hazard ratio (HR); 95% confidence intervals (95% CI)] (1.15; 95% CI 1.14-1.16, HFH (HR: 1.26; 95% CI 1.24-1.28), and the combined endpoint of total mortality or HFH (HR: 1.19; 95% CI 1.27-1.20) than CRT in patients with no previous HFHs, after co-variate adjustment. Total mortality (HR: 1.67), HFH (HR: 2.63), and total mortality or HFH (HR: 1.92) (all P < 0.001) were highest in patients undergoing CRT ≥2 years after the first HFH. In this study of a healthcare system covering an entire nation, delays from a first HFH to CRT implantation were associated with progressively worse long-term clinical outcomes. The best clinical outcomes were observed in patients with no previous HFH and in those undergoing CRT implantation during the first HFH. The optimum timing of CRT implantation is unknown. In this study of 64 968 consecutive patients, delays from a first heart failure hospitalization (HFH) to CRT implantation were associated with progressively worse long-term clinical outcomes. Each year from a first HFH to CRT implantation was associated with a 21% higher risk of total mortality and a 34% higher risk of HFH. The best outcomes after CRT were observed in patients with no previous HFHs and in those undergoing implantation during their first HFH.

Characteristics and outcomes of patients with a history of cancer recruited to heart failure trials.

Heart failure (HF) therapy trials usually exclude cancer patients. We examined the association between cancer history and outcomes in trial participants with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF). We combined PARADIGM-HF and ATMOSPHERE, which enrolled HFrEF patients (n=15 415) and we pooled HFpEF patients (ejection fraction ≥45%) enrolled in PARAGON-HF and CHARM-Preserved (n=7363). The associations between cancer history, cardiovascular (CV) death, HF hospitalization, non-CV and all-cause death in these trials were examined. Incident cancer diagnoses during these trials were also measured. There were 658 (4.3%) and 624 (8.5%) patients with a cancer history in the HFrEF and HFpEF trials, respectively. HFrEF patients with a cancer history had a higher risk of HF hospitalization (adjusted hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.07-1.52, p=0.007) and non-CV death (adjusted HR 1.57; 95% CI 1.16-2.12, p=0.003) than those without. The risks of other outcomes were similar. There were no differences in the risk of any outcome in HFpEF patients with and without a cancer history. Adjusting for age and sex, the incidence of new cancer in the HFrEF and HFpEF trials was 1.09 (95% CI 0.83-1.36) and 1.07 (95% CI 0.81-1.32) per 100 person-years, respectively. Although participants in HFrEF trials with a cancer history had higher risks of HF hospitalization and non-CV death than those without, the risks of CV and all-cause death were similar. Outcomes in HFpEF patients with and without a cancer history were similar. Incident cancer diagnoses were similar in HFrEF and HFpEF trials.

Use of and association between heart failure pharmacological treatments and outcomes in obese versus non-obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry.

To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m2 ) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.

Length of Hospitalization-Related Differences and Associated Long-Term Prognosis of Patients with Cardiac Resynchronization Therapy: A Propensity Score-Matched Cohort.

Previous studies indicated that prolonged lengths of hospitalization (LOH) during cardiac resynchronization therapy (CRT) implantation are associated with poorer physical status and higher in-hospital mortality. However, evidence on the impact of LOH on the long-term prognosis of CRT patients is limited. The purpose of this study was to assess LOH-related prognostic differences in CRT patients. In the propensity score-matched cohort, patients with standard LOH (≤7 days, n = 172) were compared with those with prolonged LOH (>7 days, n = 172) for cardiac function and study outcomes during follow-up. The study outcomes were all-cause death and heart failure (HF) hospitalization. In addition, cardiac function and changes in cardiac function at the follow-up period were used for comparison. At a mean follow-up of 3.36 years, patients with prolonged LOH, as compared with those with standard LOH, were associated with a significantly higher risk of all-cause death (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.18–2.96, p = 0.007), and a higher risk of HF hospitalization (HR 1.68, 95% CI 1.08–2.63, p = 0.023). Moreover, patients with standard LOH had a more significant improvement in cardiac function and a pronounced reduction in QRS duration during follow-up than those with prolonged LOH. LOH-associated differences were found in the long-term prognosis of CRT patients. Patients with prolonged LOH had a worse prognosis than those with standard LOH.

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients.

BackgroundGout or rapid reduction in serum uric acid level may increase the incidence of heart failure (HF). To compare the risk of HF between febuxostat and allopurinol in gout patients with coexisting cardiovascular (CV) diseases, the varying severity would be likely to confound the risk estimation. Gout and HF are both sex-related diseases, and the risk difference from the urate-lowering agents between women and men remains unknown.AimsTo evaluate the HF hospitalisations risk of febuxostat and allopurinol in gout patients in real-world settings.MethodsA population-based cohort enrolled patients with allopurinol or febuxostat initiation from 2011 to 2018. Participants were grouped into, without (low CV risk group) or with (high CV risk group) a history of recent major CV admission. The primary outcome was HF hospitalization. The secondary outcomes were composite CV events, all-cause mortality, and the cause of CV mortality. We used the ‘as-treated' analysis and Cox proportional hazards model after propensity score (PS) matching. Patients were further stratified into men and women to evaluate the gender differences.ResultsFebuxostat users had a significantly higher risk of HF hospitalization than allopurinol users in gout patients either with low CV risk [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.25–1.55] or high CV risk [HR 1.36; 95% CI 1.22–1.52]. Particularly, women with gout had a higher risk of HF hospitalization than men.ConclusionThe HF hospitalization risk was highest in gout women with high CV risk and febuxostat use. Monitoring of HF is warranted in these patients.

The Impact Of Race And Ethnicity On Clinical Outcomes In Patients With Heart Failure(On Behalf Of The Guide-IT Steering Committee)

Introduction Black and Hispanic patients (pts) with heart failure (HF) are under-represented in clinical trials. Thus, it has been challenging to understand the impact of race and/or ethnicity on clinical outcomes and responsiveness to treatment in pts with HF. Hypothesis The data in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial was used to explore racial and ethnic differences in clinical outcomes. Pts were included who were event-free at 90 days and had data on attainment of guideline-directed triple therapy (GDMT, defined as greater than 50% target dose of beta-blocker, ACEI or ARB, and any MRA dose) or target NT-proBNP ≤ 1000 pg/mL. We postulated that Black pts would have worse clinical outcomes than non-Black pts, and that Hispanic pts would have worse outcomes than non-Hispanic pts. Methods Cox proportional hazards models were used to estimate the impact of race and ethnicity on mortality and HF hospitalization. These models accounted for 3-month achievement of GDMT or target NT-proBNP, as well as previously identified prognostic characteristics. Results Of the 733 patients included, 35% were Black and 6% were Hispanic. Black pts were younger, had more co-morbidities, lower EF, and higher NYHA class vs. non-Black pts. After accounting for GDMT attainment, Black pts were at a higher risk than non-Black pts for HF hospitalization (HR=1.97, 95% CI = 1.41-2.77, p < 0.0001), but not mortality (HR = 0.70, 95% CI = 0.39-1.26, p = 0.23) (Figures 1A-1B). Hispanic pts trended towards a higher risk than non-Hispanic pts for HF hospitalization (HR=1.83, 95% CI = 0.82-4.08, p = 0.14), but not for death (HR = 0.61, 95% CI = 0.18-2.09, p = 0.43) (Figures 1C-1D). Similar patterns were observed when accounting for target NT-proBNP. Estimated effects on mortality were limited by the low mortality rate (14%). Conclusion After adjusting for GDMT or target NT-proBNP attainment, as well as prognostic characteristics, Black HF pts had a higher risk of HF hospitalization than non-Black pts. There was also a trend for higher HF hospitalization risk for Hispanic pts compared to non-Hispanic pts . Mortality results were indeterminate, but point estimates did not support an excess mortality risk for Black or Hispanic pts. Black and Hispanic patients (pts) with heart failure (HF) are under-represented in clinical trials. Thus, it has been challenging to understand the impact of race and/or ethnicity on clinical outcomes and responsiveness to treatment in pts with HF. The data in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial was used to explore racial and ethnic differences in clinical outcomes. Pts were included who were event-free at 90 days and had data on attainment of guideline-directed triple therapy (GDMT, defined as greater than 50% target dose of beta-blocker, ACEI or ARB, and any MRA dose) or target NT-proBNP ≤ 1000 pg/mL. We postulated that Black pts would have worse clinical outcomes than non-Black pts, and that Hispanic pts would have worse outcomes than non-Hispanic pts. Cox proportional hazards models were used to estimate the impact of race and ethnicity on mortality and HF hospitalization. These models accounted for 3-month achievement of GDMT or target NT-proBNP, as well as previously identified prognostic characteristics. Of the 733 patients included, 35% were Black and 6% were Hispanic. Black pts were younger, had more co-morbidities, lower EF, and higher NYHA class vs. non-Black pts. After accounting for GDMT attainment, Black pts were at a higher risk than non-Black pts for HF hospitalization (HR=1.97, 95% CI = 1.41-2.77, p < 0.0001), but not mortality (HR = 0.70, 95% CI = 0.39-1.26, p = 0.23) (Figures 1A-1B). Hispanic pts trended towards a higher risk than non-Hispanic pts for HF hospitalization (HR=1.83, 95% CI = 0.82-4.08, p = 0.14), but not for death (HR = 0.61, 95% CI = 0.18-2.09, p = 0.43) (Figures 1C-1D). Similar patterns were observed when accounting for target NT-proBNP. Estimated effects on mortality were limited by the low mortality rate (14%). After adjusting for GDMT or target NT-proBNP attainment, as well as prognostic characteristics, Black HF pts had a higher risk of HF hospitalization than non-Black pts. There was also a trend for higher HF hospitalization risk for Hispanic pts compared to non-Hispanic pts . Mortality results were indeterminate, but point estimates did not support an excess mortality risk for Black or Hispanic pts.

One year prognostic value of B-lines in dyspnoeic patients.

AbstractAimsStudies have demonstrated the reliability of B‐lines evaluated by lung ultrasonography to identify pulmonary congestion, but information is lacking about its utility as a prognostic marker of heart failure (HF). We sought to assess the prognostic midterm value of B‐lines in ambulatory patients presenting with dyspnoea, as an additive tool for patient management and to avoid acute HF exacerbations.Methods and resultsA total of 93 patients presenting with dyspnoea (New York Heart Association ≥2) were prospectively recruited in an outpatient clinic, and underwent clinical and echocardiographic evaluation, as well as B‐line evaluation with lung ultrasonography in eight zones. Primary endpoint was HF hospitalization at 1 year. A total of 88 patients were included, age 72.3 ± 9.6, with left ventricular ejection 47.7 ± 28.6%; E/e' 16.9 ± 10.9, left atrial volume 51.9 ± 22.5 mL/m2; peak tricuspid regurgitation velocity 2.6 ± 0.5 m/s, average B‐line count 7.7 ± 10. 8 (9%) patients were hospitalized for HF, seven of which had ≥6 B‐lines. B‐line cut‐off ≥6 (specificity = 66.2%; sensitivity = 87.5%) was predictive for HF hospitalization, with an odds ratio at 13.7 for HF hospitalization at 1 year [IC95% (1.6–117.4), P = 0.017].ConclusionsAmbulatory patients with ≥6 B‐lines have a higher risk of HF hospitalization at 1 year. This study highlights the prognostic value of B‐lines in evaluating HF risk in dyspnoeic patients.

Left atrial strain and outcome in heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF). However, the association between LA longitudinal strain and heart failure (HF) events in patients with HFpEF is still unknown. We evaluated whether LA strain measurements would be useful to predict hospitalizations for worsening HF in this study. Methods This study included 121 patients (Male 73, Female 48) with HFpEF who had echocardiogram at our institute (Age = 76 ± 14y, Left ventricular ejection fraction; LVEF = 63 ± 8%). Patients with atrial fibrillation were excluded. LA longitudinal strain was measured by speckle-tracking echocardiography, using TOMTEC imaging system. The endpoints were hospitalizations for worsening HF. Results During follow-up period of 319 ± 269 days, 33 patients (27%) experienced hospitalizations for worsening HF. LA strain was markedly lower in patients with HF events at 11.3 ± 5.6, whereas LA strain was higher at 20.3 ± 10.1 in patients without HF events. Kaplan-Meier analysis demonstrated a significant separation of survival curves stratified by median value of LA strain (Figure). Conclusions LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization, and LA strain measurements would be useful to predict HF events. Abstract Figure

Long-term impact of new-onset atrial fibrillation complicating acute myocardial infarction on heart failure.

AimsNew‐onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on heart failure (HF) is still not well characterized. We aimed to investigate the relationship between NOAF complicating AMI and HF hospitalization.Methods and resultsAdult AMI patients identified in the New‐Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in Shanghai registry who, discharged alive, had complete echocardiography and follow‐up data from February 2014 to March 2018 were included. Patients were divided according to the presence of NOAF. The outcome measures were HF hospitalization and death during the observational period (until 10 April 2019). Cox proportional hazard models were performed in the whole population and propensity score‐matched (PSM) cohort to assess the adjusted hazard ratio (HR) and 95% confidence interval (CI). Overall, 2075 patients (mean age: 65.2 ± 12.3 years, 77.3% were men) with AMI were analysed, of whom 228 (11.0%) developed NOAF. Advanced age, admission HF (Killip II–IV), impaired renal function, decreased left ventricular ejection fraction, increased heart rate, and left atrial enlargement were independent predictors of NOAF. Over a median observational period of 2.7 years, the annual incidence rates of HF hospitalization were 18.4% and 2.8% for patients with NOAF and sinus rhythm, respectively. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (HR: 3.14, 95% CI: 2.30–4.28, P < 0.001). Similar results were obtained when accounting for the competing risk of all‐cause death (subdistribution HR: 3.06, 95% CI: 2.18–4.30, P < 0.001) or from the PSM cohort (HR: 2.82, 95% CI: 1.99–4.00, P < 0.001). Patients with persistent NOAF (HR: 5.81, 95% CI: 3.59–9.41) were at significantly higher risk of HF hospitalization when compared with those with transient one (HR: 2.61, 95% CI: 1.84–3.70, P interaction = 0.008). Although post‐MI NOAF was significantly related to cardiovascular death (annual incidence rates for NOAF and sinus rhythm were 9.4% and 2.3%, respectively; HR: 1.97, 95% CI: 1.36–2.85, P < 0.001), such an association was attenuated when HF hospitalization (modelled as a time‐varying covariate) and antithrombotic treatment were adjusted (HR: 1.37, 95% CI: 0.92–2.02, P = 0.121).ConclusionsIn patients with AMI, NOAF is strongly associated with an increased long‐term risk of HF hospitalization. Our findings suggest that strengthened secondary prevention of HF should be considered in this high‐risk population.

Association of β-Blocker Use With Heart Failure Hospitalizations and Cardiovascular Disease Mortality Among Patients With Heart Failure With a Preserved Ejection Fraction

β-Blockers are prescribed to most patients with heart failure (HF) with a preserved ejection fraction (HFpEF), but their effect on HFpEF remains unclear. To determine the association of β-blocker use with HF hospitalizations and cardiovascular disease (CVD) mortality, overall and in strata of patients with an ejection fraction (EF) of 50% or greater or less than 50%. For 1761 participants from North and South America enrolled in the multicenter, double-blinded Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist randomized clinical trial of spironolactone for patients with HFpEF between August 10, 2006, and January 31, 2012, the association of baseline β-blocker use with HF hospitalization and CVD mortality was analyzed using unadjusted and adjusted Cox proportional hazards regression models, overall and in strata of patients with an EF of 50% or greater or less than 50%. Participants had symptomatic HF with a left ventricular EF of 45% or greater, with enrollment based on either hospitalization attributed to decompensated HF in the prior year or elevated natriuretic peptide levels. Statistical analysis was performed from January 31 to May 2, 2019. Use of β-blockers. Incident HF hospitalization and CVD mortality. Among 1761 participants included in the analysis (879 women and 882 men; mean [SD] age, 71.5 [9.6] years), 1394 (79.2%) reported β-blocker use and 1567 (89.0%) had an EF of 50% or greater. Hospitalizations for HF occurred for 399 participants (22.7%), and CVD mortality occurred for 229 participants (13.0%). Use of β-blockers was associated with a higher risk of HF hospitalization among patients with HFpEF with an EF of 50% or greater (hazard ratio, 1.74 [95% CI, 1.28-2.37]; P < .001) but not among patients with an EF between 45% and 49% (hazard ratio, 0.68 [95% CI, 0.28-1.63]; P = .39). There was a significant interaction between β-blocker use and EF threshold for incident HF hospitalizations (P = .03). Use of β-blockers was not associated with a change in CVD mortality. For patients with an EF of 50% or greater, β-blocker use was associated with an increased risk of HF hospitalizations but not CVD mortality. For patients with an EF between 45% and 49%, there was no such association.

Phenomapping of patients with heart failure with preserved ejection fraction using machine learning-based unsupervised cluster analysis.

To identify distinct phenotypic subgroups in a highly-dimensional, mixed-data cohort of individuals with heart failure (HF) with preserved ejection fraction (HFpEF) using unsupervised clustering analysis. The study included all Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) participants from the Americas (n=1767). In the subset of participants with available echocardiographic data (derivation cohort, n=654), we characterized three mutually exclusive phenogroups of HFpEF participants using penalized finite mixture model-based clustering analysis on 61 mixed-data phenotypic variables. Phenogroup 1 had higher burden of co-morbidities, natriuretic peptides, and abnormalities in left ventricular structure and function; phenogroup 2 had lower prevalence of cardiovascular and non-cardiac co-morbidities but higher burden of diastolic dysfunction; and phenogroup 3 had lower natriuretic peptide levels, intermediate co-morbidity burden, and the most favourable diastolic function profile. In adjusted Cox models, participants in phenogroup 1 (vs. phenogroup 3) had significantly higher risk for all adverse clinical events including the primary composite endpoint, all-cause mortality, and HF hospitalization. Phenogroup 2 (vs. phenogroup 3) was significantly associated with higher risk of HF hospitalization but a lower risk of atherosclerotic event (myocardial infarction, stroke, or cardiovascular death), and comparable risk of mortality. Similar patterns of association were also observed in the non-echocardiographic TOPCAT cohort (internal validation cohort, n=1113) and an external cohort of patients with HFpEF [Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial cohort, n=198], with the highest risk of adverse outcome noted in phenogroup 1 participants. Machine learning-based cluster analysis can identify phenogroups of patients with HFpEF with distinct clinical characteristics and long-term outcomes.