Initial Diagnosis Of Heart Failure Research Articles

Multicenter Descriptive Study of Monoclonal Gammopathy of Undetermined Significance in Patients with Heart Failure

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is the presence of a monoclonal immunoglobulin without concurrent lymphoproliferative disease. It is found in about 5% of people aged 50 and older in the general population. Prevalence rates of MGUS increase with age, especially in men and individuals of Black ethnicity compared to women and White individuals, respectively. The diagnostic criteria for MGUS includes a serum M-protein level <3 g/dL, <10% clonal plasma cells in the bone marrow, and the absence of a myeloma-defining event. Though historically considered benign, emerging evidence suggests that MGUS patients, even without lymphoproliferative disorders, face increased risks of various diseases like bone diseases, recurrent infections, autoimmune disorders, peripheral neuropathy, renal complications, and cardiovascular disease (CVD). This study aims to investigate the prevalence and characteristics of individuals with both MGUS and heart failure (HF) and examine potential racial disparities between Black patients and non-Black patients with MGUS and HF. Methods: This is a retrospective multicenter study that includes patients diagnosed with both MGUS and New York Heart Association grade II or higher HF from January 2010 to January 2023. Patients with potential confounding conditions of MGUS were excluded, such as non-MGUS plasma cell dyscrasias, hematologic malignancies, autoimmune/inflammatory disorders, and viral illnesses. Laboratory data was recorded at the time of MGUS diagnosis, and HF data was derived from imaging studies performed closest to the time of MGUS diagnosis or at the initial diagnosis of HF if it was diagnosed after MGUS. Findings were summarized using descriptive statistics. Results: We analyzed a total of 128 patients with MGUS and HF, excluding 24 patients with potential MGUS confounders. Among the remaining 104 patients, 41 (39.4%) were female, and 63 (60.6%) were male. The cohort consisted of 80 (76.9%) Black patients and 24 patients of non-Black ethnicity. For the overall cohort, the mean age at MGUS diagnosis was 72, and the mean time from HF diagnosis to MGUS diagnosis was 22.5 months with a median of 9.1 months. In 24% of patients, HF and MGUS were diagnosed within less than 1 month of each other. The predominant monoclonal proteins observed were IgG Kappa, IgG Lambda, and IgA Kappa, found in 54 (51.9%), 30 (28.8%), and 13 (12.5%) patients, respectively. The average M spike was 0.7 +/- 0.6 (SD, standard deviation), and the average free light chain ratio was 2.3 +/- 2.3 (SD). The most common type of HF diagnosed was heart failure with reduced ejection fraction (HFrEF, EF <40%), occurring in 63.5% of the cohort. The etiology of HF in the cohort was attributed to ischemic cardiomyopathy in 43.3%, non-ischemic cardiomyopathy in 51%, and a combination of both in 5.7%. Table 1 presents the MGUS variables for the overall cohort and stratification by race. Table 2 displays the characteristics of study subjects based on the type of HF, including HFrEF, mid-range ejection fraction (HFmrEF, EF 40-49%), and preserved ejection fraction (HFpEF, EF >50%). Conclusion: This study did not find a significant association between MGUS variables and HF, likely due to the limited sample size. However, a larger study by Schwartz et al. using a Danish nationwide database with over 8,000 participants suggested that MGUS patients had a higher risk of incident CVD, even after adjusting for other comorbidities. They also noted a higher prevalence of CVD risk factors in patients with MGUS. These findings indicate a possible link between MGUS and CVD, though the true nature of this association remains uncertain - whether it's causal or coincidental. An interesting observation from our study is that MGUS is often incidentally detected in patients already diagnosed with HF. This suggests that physicians may come across MGUS while investigating the underlying causes of HF, raising the possibility of shared underlying factors or pathological processes between both conditions. Considering our findings, it's essential to recognize that MGUS patients may have a higher mortality risk independent of developing plasma cell disorders. Large-scale studies are needed to better understand the association between MGUS and CVD, potentially influencing monitoring and follow-up strategies for MGUS patients, especially concerning potential cardiovascular implications.

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR <15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: >60, 45-59, 30-44, 15-29, or <15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR <60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or <15 compared with >60: aHR 1.75 [1.29 – 2.38], p<0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p<0.001; 90.74 [63.2 – 130.28], p<0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p<0.001) and all-cause death (2.18 [1.66 – 2.88], p<0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p<0.001) or HFpEF (3.45 [2.21 – 5.40], p<0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

Broadening Heart Failure Care Beyond Cardiology: Challenges and Successes Within the Landscape of Multidisciplinary Heart Failure Care.

Heart failure (HF) is a growing public health concern that impairs the quality of life and is associated with significant mortality. As the prevalence of heart failure increases, multidisciplinary care is essential to provide comprehensive care to individuals. The challenges of implementing an effective multidisciplinary care team can be daunting. Effective multidisciplinary care begins at the initial diagnosis of heart failure. The transition of care from the inpatient to the outpatient setting is critically important. The use of home visits, case management, and multidisciplinary clinics has been shown to decrease mortality and heart failure hospitalizations, and major society guidelines endorse multidisciplinary care for heart failure patients. Expanding heart failure care beyond cardiology entails incorporating primary care, advanced practice providers, and other disciplines. Patient education and self-management are fundamental to multidisciplinary care, as is a holistic approach to effectively address comorbid conditions. Ongoing challenges include navigating social disparities within heart failure care and limiting the economic burden of the disease.

Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure.

Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF. We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment. Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91-0.96]). Mediation analyses indicated that ≈70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant. Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.

Association Of Heart Rate At Hospital Discharge And Rehospitalization Of Patients With Heart Failure And Reduced Ejection Fraction.

One of the major causes of cardiovascular morbidity and mortality is heart failure. The study aims to assess the effect of heart rate on the incidence of rehospitalization in patients with heart failure and reduced ejection fraction. It is a cross-sectional, analytical research conducted over six months, from June to December 2022, at the cardiology department of a tertiary care hospital. Patients who satisfied the modified Framingham heart failure criteria at admission and were discharged with an initial diagnosis of heart failure and those readmitted within 6 months or less of their discharge were included in the study. Pregnant women, patients diagnosed with cognitive impairment, and patients who had contraindications for taking any of the beta-blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker /angiotensin receptor -neprilysin inhibitor, Sodium-Glucose co-transport inhibitor, and mineralocorticoid inhibitors were excluded from the study. A total of 77 patients were included in the study. At discharge, approximately 71 patients had a heart rate of less than 70 beats/min and had no readmissions whereas, 6 patients had a heart rate of greater than 70 beats/min with 5 patients requiring readmission in the following 6 months. This relationship was statistically significant with a p-value of 0.000. According to the study, heart rate is a significant factor in the rehospitalization of individuals with heart failure and a low ejection fraction. At discharge, if the heart rate is not optimized then the rate of readmissions is increased.

The spectrum of comorbidities at the initial diagnosis of heart failure a case control study

The prognosis of heart failure (HF) patients is determined to a decisive extent by comorbidities. The present study investigates the association between a broad spectrum of diseases and the occurrence of HF in a large collective of outpatients. This retrospective case control study assessed the prevalence of 37 cardiac and extracardiac diseases in patients with an initial diagnosis of heart failure (ICD-10: I50) in 1,274 general practices in Germany between January 2005 and December 2019. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without heart failure were matched by sex, age, and index year. Hazard regression models were conducted to evaluate the association between different disease entities and heart failure. The present study included 162,246 patients with heart failure and 162,246 patients without heart failure. Mean age [SD] was 73.7 [12.1] years; 52.6% were women. Out of 37 predefined diagnoses, 36 were more prevalent in HF patients. The highest prevalence was primary hypertension (63.4% in HF patients vs. 53.3% in controls, p < 0.001) followed by lipid metabolism disorders (34.6% in HF patients vs. 29.1% in HF patients p < 0.001) and diabetes mellitus type II (32.2% in HF patients vs. 25.2% in controls, p < 0.001). In the regression analysis, 19 diseases were significantly associated with heart failure. Non-cardiovascular diagnoses strongly associated with HF were obesity (HR = 1.46), chronic bronchitis and COPD (HR = 1.41), gout (HR: 1.41), and chronic kidney disease (HR = 1.27). In the present study, we identified a variety of cardiac and extracardiac diseases associated with heart failure. Our data underscore the immense importance of comorbidities, even as early as at the stage of initial diagnosis of heart failure.

Heart failure is associated with an increased incidence of cancer diagnoses

AimsThe prognosis and quality of life of heart failure patients is determined to a significant extent by co‐morbidities. New data suggest that heart failure may be associated with an increased incidence of cancer. The present retrospective study investigates this association in a large collective of outpatients with heart failure.Methods and resultsThis retrospective cohort study assessed the incidence of cancer in patients with an initial diagnosis of heart failure and a matched non‐heart failure cohort in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyser database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Hazard regression models were used to study the association between heart failure and the incidences of different cancers. A total of 100 124 patients with heart failure and 100 124 patients without heart failure were included in the analysis. Patients were matched individually by sex, age, diabetes, obesity, and yearly consultation frequency. Within the 10 year observation period, 25.7% of patients with heart failure and 16.2% of patients without heart failure had been diagnosed with cancer (log‐rank P < 0.001). These proportions were 28.6% vs. 18.8% in female and 23.2% vs. 13.8% in male patients. Heart failure was significantly associated with the incidence of cancer [hazard ratio (HR), 95% confidence interval: 1.76, 1.71–1.81; P < 0.001 in total; HR: 1.85, 1.77–1.92, P < 0.001 in women; HR: 1.69, 1.63–1.76, P < 0.001 in men]. A significant association was found between heart failure and all cancer sites assessed. The strongest association was observed for cancer of lip, oral cavity, and pharynx (HR: 2.10, 95% confidence interval: 1.66–2.17; P < 0.001), followed by respiratory organs (HR: 1.91, 1.74–2.10; P < 0.001) and genital organs of female patients (HR: 1.86, 1.56–2.17; P < 0.001). The association for skin tumours was 1.83 (1.72–1.94; P < 0.001), for cancer of lymphoid and haematopoietic tissue 1.77 (1.63–1.91; P < 0.001), for cancer of the digestive tract 1.75 (1.64–1. 87; P < 0.001), for breast cancer 1.67 (1.52–1.84; P < 0.001), for cancer of the genitourinary tract 1.64 (1.48–1.81; P < 0.001), and for male genital organ cancer 1.52 (1.40–1.66; P < 0.001).ConclusionsOur study indicates that heart failure patients experience a significantly higher incidence of cancer during the course of the disease.

Predictors of relapse after improved ejection fraction in patients with heart failure

Abstract Background Patients with systolic dysfunction with improvement in left ventricular ejection fraction (LVEF) present a more favorable clinical profile when compared to those that maintain dysfunction. However, little is known about the characteristics of patients who “relapse” after LVEF improvement. Purpose Evaluate prevalence, clinical characteristics and outcomes of patients in whom ejection fraction declined after previous improvement. Methods We retrospectively studied patients followed at a heart failure (HF) clinic with LVEF improvement after an initial diagnosis of HF with reduced ejection fraction (EF), which was defined as having an LVEF &amp;gt;40% on follow-up. We then evaluated the presence of LVEF “relapse” in these patients – a decline in LVEF to &amp;lt;50% or &amp;lt;40%, in cases where it recovered to preserved EF or to mid-range EF, respectively. We analysed patient demographics, clinical parameters and outcomes and used logistic regression to assess the predictors of LVEF “relapse”. Results 98 patients were studied, 70 (71%) male, median age 69 (58–76) years. Fifty-four (55%) patients had recovered EF (&amp;gt;50%) and in 44 (45%) it had improved to mid-range values. In 36 (37%) occurred LVEF “relapse”: in 10 (10%) patients to an EF 40–50% and in 88 (90%) to an EF&amp;lt;40%. Ischemic cardiomyopathy and non-ischemic dilated cardiomyopathy were the main HF aetiologies (38% and 35%, respectively). During a median follow-up of 7 years, 39 (40%) patients had at least one HF hospitalization. Global mortality was 30%, with no significant statistical difference between the two groups. In univariate analysis, HF duration, type 2 diabetes mellitus (T2DM), left main or left anterior descending coronary (LAD) disease, valvular heart disease (VHD) and chronic kidney disease (CKD) predicted LVEF “relapse”. In multivariate analysis, T2DM, left main or LAD disease and VHD were the only predictors of LVEF “relapse” (Table). Conclusion In this group of patients, LVEF “relapse” after it had initially improved was frequent and was predicted by the presence of T2DM, left main or LAD disease and VHD. Despite improved systolic function, these patients remain at high risk, thus the need to maintain treatment. Funding Acknowledgement Type of funding source: None

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)

Abstract Background Little is known about the impacts of sodium glucose co-transporter 2 inhibitors on cardiac functional parameters, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). Purpose To compare the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population. Methods This trial was an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint trial at 34 centers in Japan. Patients with T2D and clinically stable CHF excluding NYHA class IV, randomized to receive canagliflozin 100 mg or glimepiride (starting dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin versus glimepiride, defined as a margin of 1.1 in the upper-limit of the 2-sided 95% confidence interval (95% CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Results Data analysis of 233 patients (mean age 68.6±10.1 yrs; 75% male) showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6±14.6%, with 71% of patients having a preserved LVEF (≥50%). The ratio of NT-proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P=0.226), and therefore did not meet the prespecified non-inferiority margin. However, data stratified according to baseline NT-proBNP levels showed a trend that canagliflozin treatment reduced NT-proBNP levels to a greater extent than in subgroups with elevated levels of NT-proBNP (Figure A). Furthermore, NT-proBNP levels in the canagliflozin group did show a nonsignificant trend lower in the subgroup with preserved LVEF (Figure B), but not in the subgroup with reduced LVEF (Figure C). Additionally, the changes in the NYHA class were comparable between groups (P=0.061) in the overall cohort, whereas in the subgroup with a preserved LVEF canagliflozin caused a significant improvement in NYHA classes compared to that found for glimepiride treatment (P=0.027). Conclusions This trial did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin relative to glimepiride which together with other recent studies would question the value of continuing to monitor NT-proBNP levels after the initial diagnosis of heart failure. Nevertheless, in a subgroup with preserved LVEF, there was a non-significant trend for canagliflozin treatment to reduce NT-proBNP levels and improve symptoms even in stable HF patients. Further research is therefore warranted to determine whether patients with preserved LVEF, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors. Changes in NT-proBNP Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Mitsubishi Tanabe Pharma Corporation

Intracardiac Thrombus in Sinus Rhythm: A Case of Missed Cardiac Amyloidosis

Intracardiac thrombus in patients with amyloid cardiomyopathy in sinus rhythm is a rare phenomenon, and no guidelines currently exist regarding screening, diagnosis, or management. We describe a case of a 59 year-old female who presented to the hospital with dyspnea on exertion, orthopnea, pedal edema, and weight gain. She had a one year history of heart failure with preserved ejection fraction, treated with metoprolol, bumetanide, and metolazone, and three month history of AL amyloidosis, treated with Bortezomib and Dexamethasone. Upon admission, labs showed leukocytosis, thrombocytosis, and elevated troponin and BNP. Electrocardiogram revealed sinus rhythm with left atrial enlargement. CT chest angiography showed pulmonary edema and a hypodense mass in the right atrium/atrial appendage. Cardiac magnetic resonance imaging demonstrated moderate concentric hypertrophy, elevated native T1 (1126 ms), diffuse late gadolinium enhancement, and elevated ECV (52%) consistent with cardiac amyloidosis. A right atrial mass consistent with a thrombus was visualized. Intracardiac thrombus was treated with intravenous heparin, which was transitioned to warfarin. Volume overload secondary to AL-cardiac amyloidosis was managed with diuresis. She was discharged home with hospice and passed approximately one month later. This case illustrates a missed diagnosis of cardiac involvement of systemic AL amyloidosis, ultimately resulting in death within nearly one year from initial diagnosis of heart failure. It also explores the etiology, diagnosis, and treatment of an intracardiac thrombus in patients with cardiac amyloidosis in sinus rhythm. Therefore, this case demonstrates the need for evidence-based guidelines regarding stratification of thrombotic risk and serial monitoring in patients with cardiac amyloidosis without arrythmia. Furthermore, it exemplifies the importance of high suspicion for cardiac amyloidosis to guide early diagnosis and management of patients with cardiac involvement of systemic amyloidosis, in addition to screening and monitoring of associated comorbidities, to improve prognosis and overall survival.

Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.

More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.

6129Temporal trends and patterns in cause-specific mortality and hospitalisations after incident heart failure: a longitudinal analysis of 86,000 individuals

Abstract Background The past two decades have brought considerable improvements in heart failure care. Clinical trials have demonstrated effectiveness of several different treatments in reducing mortality and hospitalisations, and observational studies have shown that these treatments are increasingly being used in many countries. Little is known about whether these changes have been reflected in patient outcomes in routine clinical settings. Methods We used anonymised electronic health records that link information from primary care, secondary care, and the national death registry to investigate 86,000 individuals with newly diagnosed heart failure between 2002 and 2013 in the UK. We computed all-cause and cause-specific mortality rates and number of hospitalisations in the first year following diagnosis. We used Poisson regression models to calculate category-specific rate ratios and 95% confidence intervals, adjusting for patients' age, sex, region, socioeconomic status and 17 major comorbidities. Findings One year after initial heart failure diagnosis, all-cause mortality rates were high (32%) and did not change significantly over the period of study (adjusted rate ratio (RR) 2013 vs 2002: 0.94 [0.88, 1]). Overall rates masked diverging trends in cause-specific outcomes: a decline in cardiovascular mortality (RR: 0.74 [0.68, 0.81]) was offset by an increase in non-cardiovascular mortality (RR: 1.28 [1.17, 1.39]), largely due to infections and chronic respiratory conditions. Sub-group analyses further showed that overall mortality declined among patients under 80 years of age (RR 2013 vs 2002: 0.79 [0.71, 0.88]), although not in older age groups (RR 2013 vs 2002: 0.97 [0.9, 1.06]). After cardiovascular causes (43%), the major causes of death identified in 2013 were neoplasms (15%), respiratory conditions (12%), and infections (11%). Hospital admissions within a year of heart failure diagnosis were common (1.15 hospitalisations per patient-year at risk), changed little over time (RR: 0.96 [0.92, 0.99]), and were largely (60%) due to non-cardiovascular causes. Interpretation Despite increased use of life-saving interventions, overall mortality and hospitalisations following a new diagnosis of heart failure have changed little over the past decade. Improved prognosis among young and middle-aged patients marks an important achievement and attests of complex barriers to progress in elderly patients. The shift from cardiovascular to non-cardiovascular causes of death suggest that management of associated comorbidities might offer additional opportunities to improve patients' prognosis. Acknowledgement/Funding British Heart Foundation, National Institute for Health Research, UK Research and Innovation.

Associations between residential exposure to fine particulate matter and days spent in hospital for heart failure patients

TPS 681: Short-term health effects of air pollutants 1, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Heart failure (HF) is a severe form of cardiovascular disease which is increasing in prevalence. Mortality risks from elevlated ambient fine particulate matter (PM2.5) exposure are well characaterized for HF patients, but few studies have examined morbidity risks in the HF community. In particular, measures such as the days spent in hospital, which may correlate with quality of life and healthcare costs, have yet to be explored. Methods: Using the EPA CARES resource, we examined associations between annual average PM2.5 exposure (assessed at the primary residence at the time of initial HF diagnosis) and the total visits, number of emergency plus inpatient visits, and total days spent in hospital for 24,798 North Carolina resident HF patients (559,664 total visits, 7.7% inpatient or emergency) who resided <30 km from a PM2.5 monitor. The observation period was 7/1/2004 to 12/31/2016. Models were adjusted for age at diagnosis, sex, race, and socioeconomic status indicators extracted from the 2000 census. We used a quasipoisson model to model the total visits and inpatient plus emergency visits and a linear model for the log-transformed total days spent in hospital. Results: The average PM2.5 exposure was 10.2 µg/m3 (interquartile range 8.4-11.4 µg/m3). A 1 µg/m3 increase in PM2.5 exposure was associated with a 19% increase (95% confidence interval [CI] = 18-19%) in the total number of visits, an 11% increase (CI = 11-12%) in the number of inpatient and emergency visits, and a 4.4% increase (CI = 3.7-5.2%) in the total days spent in hospital. Conclusions: Elevated PM2.5 exposure is a significant morbidity risk factor for HF patients. Increases in the number of hospital visits and the days spent in hospital are likely related to quality of life as well as healthcare costs for HF patients. This abstract does not necessarily represent EPA policy.

Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial

ObjectivesThe purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). BackgroundBucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. MethodsA total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period. ResultsThe hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011). ConclusionsPharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.

LSTM Model for Prediction of Heart Failure in Big Data.

The combination of big data and deep learning is a world-shattering technology that can make a great impact on any industry if used in a proper way. With the availability of large volume of health care datasets and progressions in deep learning techniques, systems are now well equipped in diagnosing many health problems. Utilizing the intensity of substantial historical information in electronic health record (EHR), we built up, a conventional predictive temporal model utilizing recurrent neural systems (RNN) like LSTM and connected to longitudinal time stepped EHR. Experience records were contribution to RNN to anticipate the analysis and prescription classes for a resulting visit during heart disappointment (e.g. diagnosis codes, drug codes or method codes). In this paper, we also investigated whether use of deep learning to model temporal relations among events in electronic health records (EHRs) would enhance the model performance in predicting initial diagnosis of heart failure (HF) compared to some of the traditional methods that disregard temporality. By examining these time stamped EHRs, we could recognize the associations between various diagnosis occasions and finally predicate when a patient is being analyzed for a disease. In any case, it is hard to access the current EHR data straightforwardly, since almost all data are sparse and not standardized. Along these lines, we proposed a robust model for prediction of heart failure. The fundamental commitment of this paper is to predict the failure of heart by means of a neural network model based on patient's electronic medicinal information. In order to, demonstrate the diagnosis events and prediction of heart failure, we used the medical concept vectors and the essential standards of a long short-term memory (LSTM) deep network model. The proposed LSTM model uses SiLU and tanh as activation function in the hidden layers and Softmax in output layer in the network. Bridgeout is used as a regularization technique for weight optimization throughout the network. Assessments subject to the real-time data exhibit the favorable effectiveness and feasibility of recommended model in the risk of heart failure prediction. The results showed improved accuracy in heart failure detection and the model performance is compared using the existing deep learning models. Enhanced prior detection could expose novel chances for deferring or anticipating movement to analysis of heart failure and diminish cost.

Clinical Course of Patients With Worsening Heart Failure With Reduced Ejection Fraction

BackgroundEpidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described. ObjectivesThe purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting. MethodsData on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed. ResultsOf 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p < 0.001). At the onset of worsening HF, 42.4% of patients were on monotherapy, 43.4% were on dual therapy, and 14.1% were on triple therapy. A total of 48%, 61%, and 98% of patients were on >50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event. ConclusionsIn the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.

Brain natriuretic peptide as a diagnostic marker for heart failure in hyperthyroid patients with ischemic heart disease

ObjectiveThe aim of the study was to evaluate the value of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as an early diagnostic marker for chronic heart failure (CHF) in hypothyroid patients with ischemic heart disease (IHD).Materials and methodsA total of 120 patients with an age range between 42 and 64 years participated in the study. All patients were classified into four groups: the master first group includes 30 patients with IHD, CHF functional class II–III and hyperthyroidism; the second group includes 30 patients with IHD and CHF functional class II–III, but with normal thyroid function; the third group includes 30 hyperthyroid patients without CHF or IHD; and the fourth group includes 30 hyperthyroid patients with IHD, without CHF. All patients were subjected to the following: full clinical and functional assessment, measurement of NT-proBNP, echocardiography, and the 6-min walk test.ResultsNT-proBNP levels were high in all studied groups. NT-proBNP levels showed no significant difference between patients of second and fourth group. The master first group had the highest significant NT-proBNP concentrations than other studied groups. Thyroid hyperfunction in patients with IHD appears to stimulate the natriuretic peptides secretion at a level exceeding what is recommended for the initial diagnosis of CHF.ConclusionThe highest NT-proBNP level in hyperthyroid patients with IHD apparently is caused by stimulation of natriuretic peptide secretion by both thyroid hyperfunction and myocardial ischemic changes, which determine the need to check out the cut-off value of NT-proBNP level as a serological marker for the initial diagnosis of heart failure of such patients’ category.

Abstract 235: Revascularization Patterns of Systolic Heart Failure in a Large Urban County Hospital

Background: Coronary angiography is frequently performed after the initial diagnosis of heart failure to determine etiology and revascularization strategy. Current body of evidence suggests that surgical revascularization conveys a mortality benefit as compared to medical therapy alone, and the role of percutaneous coronary intervention (PCI) is not yet established. The aim of this study is to describe revascularization patterns among patients presenting with systolic heart failure who underwent diagnostic angiography at a large urban county hospital. Methods: We evaluated patients presenting to the emergency department with symptomatic heart failure with reduced ejection fraction (HFrEF) without acute coronary syndrome (n=150; average left ventricular ejection fraction of 25%) who underwent coronary angiography between January 2011 and January 2015. We defined surgical coronary artery disease (CAD) as: 1) three-vessel disease, 2) two-vessel disease including the proximal LAD artery, or 3) two-vessel disease including the left main coronary artery. Primary outcomes included intervention (PCI, CABG, or medical therapy [MT] alone) as well as referral for CABG. Results: Of patients presenting with HFrEF who underwent diagnostic angiography, 80% (n=120) of patients had obstructive CAD with 36% (n=43) of those patients having surgical CAD. Of those with surgical CAD, 74% (n=32) underwent PCI, 18% (n=8) underwent CABG and 7% (n=3) received MT alone. Of patients with 1-vessel CAD, or 2-vessel CAD without involvement of the proximal LAD artery or left main coronary artery, 81% (n=63) underwent PCI while 19% (n=14) received MT alone. Conclusion: Patients presenting with symptomatic HFrEF referred for cardiac catheterization have a high prevalence of obstructive CAD. Most patients with evidence of either surgical or non-surgical CAD during coronary angiography underwent revascularization, with PCI being the dominant revascularization method.

Using recurrent neural network models for early detection of heart failure onset.

Objective: We explored whether use of deep learning to model temporal relations among events in electronic health records (EHRs) would improve model performance in predicting initial diagnosis of heart failure (HF) compared to conventional methods that ignore temporality. Materials and Methods: Data were from a health system’s EHR on 3884 incident HF cases and 28 903 controls, identified as primary care patients, between May 16, 2000, and May 23, 2013. Recurrent neural network (RNN) models using gated recurrent units (GRUs) were adapted to detect relations among time-stamped events (eg, disease diagnosis, medication orders, procedure orders, etc.) with a 12- to 18-month observation window of cases and controls. Model performance metrics were compared to regularized logistic regression, neural network, support vector machine, and K-nearest neighbor classifier approaches. Results: Using a 12-month observation window, the area under the curve (AUC) for the RNN model was 0.777, compared to AUCs for logistic regression (0.747), multilayer perceptron (MLP) with 1 hidden layer (0.765), support vector machine (SVM) (0.743), and K-nearest neighbor (KNN) (0.730). When using an 18-month observation window, the AUC for the RNN model increased to 0.883 and was significantly higher than the 0.834 AUC for the best of the baseline methods (MLP). Conclusion: Deep learning models adapted to leverage temporal relations appear to improve performance of models for detection of incident heart failure with a short observation window of 12–18 months.

Heart failure hospitalization: An important prognostic factor for heart failure re-admission and mortality

BackgroundFew studies have evaluated incidence rates and risk factors for heart failure hospitalization (HFH) and mortality starting at initial heart failure (HF) diagnosis. MethodsPatients with a first ever recorded diagnosis of HF between January 2000 and December 2005 (N=3516) were identified from The Health Improvement Network primary care database and followed until April 2011 to identify HFHs (through linked hospitalization data) and deaths. HF patients were stratified by hospitalization status at HF diagnosis (start date), and hazard ratios (HRs) for HFH and death were estimated using Cox regression. Predictors of HF re-admission were identified by nested case–control analysis among patients hospitalized at start date, using patients with a new HFH during follow-up as cases and a set of age and sex matched controls. ResultsDuring a mean follow-up of 4.5years, 32% of incident HF patients (n=1119) had a HFH and 58.5% died (n=2056). Compared with patients not hospitalized at initial HF diagnosis (N=2759), a two-fold increased risk of HFH during follow-up, consistent over time, was seen in patients hospitalized at initial HF diagnosis (N=757); adjusted HR 2.14 (95% CI: (1.88–2.44). Major predictors of HFH were renal impairment, diabetes and prior HFH. Mortality rates were higher in HF patients hospitalized at initial HF diagnosis, but the major determinant of mortality was HFH during follow-up: HR 3.88 (95% CI: 3.53–4.26) irrespective of HFH status at initial diagnosis. ConclusionPatients hospitalized at initial HF diagnosis or with a HFH thereafter are at high risk of worse outcomes.