New-onset Heart Failure Research Articles

Ischemic Evaluation in New-Onset Methamphetamine-Associated Heart Failure.

Ischemic Evaluation in New-Onset Methamphetamine-Associated Heart Failure.

Incident heart failure: comparing management and outcome in primary and hospital settings in Western Sweden 2008-2017.

Heart failure (HF) is a highly prevalent condition managed in both primary care (PC) and hospital care (HC)-based settings. HF patients managed in these two settings may differ in their demography, comorbidities and outcomes, so we aimed to compare the patient management in PC and HC in the Västra Götaland Region (VGR) in Sweden. The VEGA database is an administrative database that includes all patients living in VGR. Patients with a first principal or contributory diagnosis of HF (I50) ≥18years old between 2008 and 2017 were included. One-year mortality was used as the outcome. In total, 35375 new-onset HF cases were included with 18722 identified only in PC and 16651 in HC. HF patients in PC were older (80.7±10.9 vs. 76.1±13.6), more women (57.1% vs. 44.9%), with more hypertension, musculoskeletal and mental disorders, but less myocardial infarction. Patients in HC had almost 4 times higher all-cause 1year mortality [3.92 (3.77-4.08), P<0.0001] compared with PC after adjustment for age and sex. Over a 10year period, despite decreasing mortality in both settings, hazard ratios for HC versus PC were significantly increased for all patients (P for interaction 0.0004), which was more marked in female and for 70-80years old patients. Over a 10year period, we demonstrated the differences in demography, comorbidities and outcomes between heart failure patients managed in hospital care versus primary care.

Abstract 4134949: Effect of anakinra in patients with ST-elevation myocardial infarction according to the renal function

Introduction: Interleukin(IL)-1 blockade with anakinra dampens the inflammatory response and prevents heart failure (HF) events in patients with ST-elevation myocardial infarction (STEMI). The efficacy of anakinra according to the baseline renal function in STEMI has not been addressed. Hypothesis: The efficacy of anakinra is independent of the baseline renal function. Aim: To determine the effect of anakinra according to the baseline renal function in patients with STEMI. Methods: We pooled patients with STEMI from 3 double-blind randomized clinical trials. Patients with estimated glomerular filtration rate (eGFR) &lt;15 mL/min/1.73m2 were excluded. We divided the cohort based on the median baseline eGFR using the modified 2021 CKD-EPI equation (≥ or &lt; 86 mL/min/1.73m2). We analyzed the area-under-the-curve for C-reactive protein (AUC-CRP) at 14 days, and the incidence of the composite outcome of all-cause death or new-onset HF at 1 year using the Log-rank test. We also evaluated the creatinine changes at 48-72 hours after percutaneous coronary intervention (PCI). Results: We analyzed 139 patients, 110 (79%) males, 52 (37%) Black or African-American, with a median age of 56 [49–63] years. The AUC-CRP at 14 days was significantly higher in patients receiving placebo vs. anakinra both in those with eGFR &lt;86 mL/min/1.73m2 (250.5[131.4-512.0] vs. 66.4[42.3-126.5] mg●day/L, p&lt;0.001) and those with eGFR ≥86 mL/min/1.73m2 (214.2[113.6-303.4] vs. 86.4[35.9-194.3] mg●day/L, p&lt;0.01). Anakinra significantly reduced the composite outcome of all-cause death or new-onset HF in patients with baseline eGFR &lt;86 mL/min/1.73m2 (4/41 [9.8%] vs. 9/27 [33.3%], Log-rank p=0.024) as well as in patients with baseline eGFR ≥86 mL/min/1.73m2 (3/43 [6.9%] vs. 7/28 [25%], Log-rank p=0.038)(p=0.97 for interaction)(Figure). No differences in creatinine changes 48-72 hours after PCI were observed (0.01 [-0.10 to 0.15] mg/dL in anakinra vs. 0.01[-0.08 to 0.14] mg/dL in placebo; p=0.80). Conclusion: In a cohort of patients with STEMI and mainly preserved or mildly reduced renal function, IL-1 blockade with anakinra blunts the acute inflammatory response and prevents all-cause death or new-onset HF at 1 year independent of baseline renal function.

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

Abstract 4135905: The Impact of Emergent Atrial Fibrillation in Patients With Newly Diagnosed Heart Failure and Differences in Risk Among Preserved vs. Reduced Ejection Fraction

Background: Atrial fibrillation (AF) and heart failure (HF) are associated with an increased risk of adverse events, with their diagnoses often coexisting. The impact of AF in HF needs additional study, with further delineation among HF type. Therefore, this study sought to determine the degree of AF burden among newly diagnosed HF patients and whether differences in risk exist between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients. Methods: Patients with new-onset HF between 2000-2019 were studied. To be included, patients had to have 1-year of follow-up, an ejection fraction (EF) measurement within 30 days of HF diagnosis, and no history of cancer. EF was used to define HFrEF (EF &lt;40%) and HFpEF (EF &gt; 40%). Multivariable Cox hazard regression was used to evaluate the risk of death and HF hospitalization at 1- and 3-years. Results: A total of 21,925 patients were studied with HFrEF (n=7931 [36.2%]) and HFpEF (n=13,994 [63.8%]). HFpEF patients were older (74 vs. 65 years) and more often female (53.7% vs. 33.1%). Prevalent AF was 40.5% (n=8879), being more common in HFpEF compared to HFrEF (65.2% vs. 34.8%). Among AF patients, HFpEF patients were also older (76 vs. 72 years) and more often female (52.7% vs. 30.8%) compared to HFrEF. The presence of AF was associated with an increased risk of HFpEF (OR=1.11, p=0.001). Prevalent AF was associated with an increased risk of death and follow-up HF hospitalization (Table). Death at 1-year and 3-years were similar between the HF groups (Table). However, the risk of HF hospitalization was greater among HFrEF patients (Table). Similar associations persisted when AF patients were propensity matched (Table). Conclusions: Among a newly diagnosed HF population, AF was common (40%) and was associated with an increased risk of HFpEF, death, and HF hospitalization. These results provide a rationale for aggressive management of HF and AF patients and the need for a randomized clinical trial to determine optimal therapy by ablation and 4-pillar HF therapy.

Abstract 4117731: Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Interleukin-1 (IL-1) blockade with Anakinra inhibits the acute inflammatory response and prevent HF after STEMI, but data on its effects based on CAD complexity are lacking. Aims: To assess the effects of Anakinra in patients with STEMI, across the spectrum of CAD complexity. Methods: We performed a pooled secondary analysis of 139 patients with STEMI from three randomized clinical trials (VCUART studies) comparing Anakinra (N=84) versus placebo (N=55). Multivessel CAD was defined as the presence of at least one ≥70% stenosis in a non-culprit vessel of &gt;2.5 mm diameter, not stented during index coronary intervention. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided by the median. We evaluated a composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios, and calculated interactions between groups. Results: We included 139 patients with STEMI, 85 (61%) with single vessel CAD and 54 (39%) with multivessel CAD. According to the spectrum of CAD complexity, 60 (43%) presented a SYNTAX score &gt;9, 59 (42%) a SYNTAX II score &gt;24 and 65 (47%) a Gensini score &gt;32. New-onset HF, HF hospitalization, or all-cause death occurred in a total of 23 patients: 7 among the 84 subjects in the Anakinra group and 16 within the 55 patients in the placebo group. We found no statistically significant interactions between CAD complexity and allocation to Anakinra or placebo for the composite endpoint (Figure). Conclusions: Among patients with STEMI, IL-1 blockade with Anakinra significantly reduced the risk of new-onset HF, HF hospitalization, or all-cause death compared to placebo, regardless of the number of vessels affected and the spectrum of CAD complexity.

Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided into two groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios (HR), and tested interactions between subgroups. All three CAD complexity scores (SYNTAX, SYNTAX II and Gensini) were associated with an increased risk of adverse events (HR 1.02 to 1.06, all p-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multi-vessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all p-values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

Abstract 4138339: Abatacept prevents anti-PD-1-induced inflammatory heart failure development after myocardial ischemic injury in mice

Introduction: Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure. Hypothesis: We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunction and inflammation caused by anti-PD-1 treatment. Moreover, we investigated whether abatacept, a T-cell co-stimulation blocker, can prevent ICI-induced cardiac effects. Methods: To induce reversible cardiac ischemia, C57Bl/6J mice were treated with isoprenaline (ISOP group) or with PBS (CON group), followed by 16 weeks of recovery period. Following this, mice from both groups were divided into three further treatment groups: isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, and were treated for two weeks, with three weekly intraperitoneal injections. Echocardiography was performed to evaluate cardiac function while myocardial inflammation was assessed by qRT-PCR and immunohistochemistry. Flow cytometry and Western blot were used to investigate changes occurring in the thymus. Results: Mice with normal heart function but with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1) showed significantly decreased fractional shortening and cardiac index on echocardiography, while in animals with abatacept co-treatment (ISOP+anti-PD-1+abatacept) cardiac function was not altered. Increased immune cell infiltration was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, including T-cells and macrophages, with increased expression of pro-inflammatory cytokines, while co-treatment with abatacept ameliorated the inflammatory response. In the thymus, increased expression of PD-1 was found after abatacept co-treatment. Conclusion: Prior myocardial ischemic injury was associated with cardiac dysfunction and inflammation after anti-PD-1 treatment, which was ameliorated by abatacept co-treatment. Patients with prior cardiac ischemic events may be at greater risk for developing ICI-induced cardiotoxicity, including new-onset HF.

Associations of SGLT2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Patients ≥ 18years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2years from HT initiation. After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality. Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Prognostic impact of iron deficiency in new-onset chronic heart failure: Danish Heart Failure Registry insights.

Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition. This study evaluates the prevalence and the prognostic impact of ID using different criteria on all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF. In this nationwide registry-based cohort, we explored four definitions of ID: the current European Society of Cardiology (ESC) guidelines [ferritin <100ng/mL or ferritin 100-299ng/mL and transferrin saturation (TSAT) <20%], ferritin level <100ng/mL, TSAT<20% and serum iron ≤13μmol/L. Patients were identified through the Danish Heart Failure Registry. Of 9477 new-onset chronic HF patients registered in the Danish Heart Failure Registry from April 2003 to December 2019, we observed ID prevalence rates ranging from 35.8% to 64.3% depending on the ID definition used. Among patients with ID defined by iron ≤13μmol/L or TSAT<20%, 26% and 15.5%, respectively, did not meet the ESC guidelines definitionfor ID. Conversely, 11% of patients meeting the ESC criteria exhibited serum iron >13μmol/L and TSAT>20%. Regardless of anaemia status, ID defined by TSAT<20% or serum iron ≤13μmol/L was associated with all-cause mortality [non-anaemic, hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.30-1.89 and HR: 1.47, 95% CI: 1.24-1.73; anaemic, HR: 1.22, 95% CI: 1.07-1.38 and HR: 1.25, 95% CI: 1.09-1.44, respectively] and cardiovascular mortality (non-anaemic, HR: 2.21, 95% CI: 1.59-3.06 and HR: 1.47, 95% CI: 1.12-1.95; anaemic, HR: 1.37, 95% CI: 1.11-1.69 and HR: 1.28, 95% CI: 1.02-1.61, respectively), as well as increased risk of first hospitalization for HF (non-anaemic, HR: 1.28, 95% CI: 1.09-1.1.50 and HR: 1.27, 95% CI: 1.10-1.46; anaemic, HR: 1.25, 95% CI: 1.08-1.44 and HR: 1.22, 95% CI: 1.05-1.42, respectively). ID defined by ESC guidelines was associated with all-cause and cardiovascular mortality only in non-anaemic patients (HR: 1.41, 95% CI: 1.18-1.1.70 and HR: 1.58, 95% CI: 1.18-2.12.). Furthermore, the ESC guideline definition was associated with increased risk of first hospitalization for HF, regardless of anaemia status (non-anaemic, HR: 1.26, 95% CI: 1.08-1.1.47; anaemic, HR: 1.34, 95% CI: 1.17-1.53). ID, when defined by TSAT<20% or serum iron ≤13μmol/L, is associated with increased risk of all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF, regardless of anaemia status. Conversely, ID defined as ESC guidelines is associated with all-cause and cardiovascular mortality only in non-anaemic patients.

Hospitalized Advanced HeartFailure With Preserved vs Reduced Left Ventricular Ejection Fraction: A Global Perspective.

Outcomes of hospitalized patients with heart failure (HF) and characteristics of advanced HF stage may vary across left ventricular ejection fraction (LVEF) and world regions. This study sought to analyze characteristics of hospitalized advanced HF patients across LVEF spectrum, world regions, and country income. Among 18,553 hospitalized patients with acute HF (7,902 new-onset HF and 10,651 decompensated chronic HF) enrolled in the global registry REPORT-HF (International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of HeartFailure), we analyzed characteristics and outcomes of patients with advanced HF, defined as previously diagnosed HF; severe symptoms before current admission (NYHA functional class III/IV); and≥1 HF-related hospitalization in the preceding 12months, excluding the current. Differences among hospitalized advanced HF subgroups stratified by LVEF, world region, and country income were examined. Among 6,999 patients with decompensated chronic HF and available previous NYHA functional class and HF hospitalization status, 3,397 (48.5%; 18.3% of the total population) had advanced HF. Of these, 44.5% had severely reduced (≤30%), 34.9% mildly/moderately reduced (31%-49%), and 20.7% preserved (≥50%) LVEF. Patients from Eastern Europe had the lowest 1-year mortality (23%), whereas those from Southeast Asia had the highest (37%). Patients from lower-middle-income countries were younger, with shorter HF duration and lower comorbidity prevalence, received fewer beta-blockers and HF-devices, and had higher 1-year mortality (34%) than upper-middle- (26%) or high-income countries (27%; P=0.018). Adjusted 1-year mortality risk did not differ among LVEF subgroups (all P > 0.05), nor did 1-year HF hospitalization rate (P=0.56). Hospitalized patients with advanced HF and preserved LVEF had similarly adverse outcomes as those with reduced LVEF. Patients from lower-middle-income countries had less implementation of HF therapies and higher 1-year mortality.

Metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes: risk of heart failure

Background and aimsThe association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is unclear. This study aimed to investigate the impact of spectrum of SLD on the risk of heart failure and cardiovascular (CV) mortality in patients with T2DM.MethodsIn a nationwide cohort study, 2,745,689 adults with T2DM were followed from 2009 to 2012 until 2018. Participants were categorized into no steatotic liver disease (no SLD) and SLD groups. The SLD group was stratified based on metabolic risk factors, alcohol consumption and viral hepatitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for heart failure (HF) and CV mortality risk.ResultsThe prevalence of MASLD, metabolic alcohol-associated liver disease (MetALD), alcohol-associated liver disease with metabolic dysfunction (ALD with MD) and MASLD with viral hepatitis (VH) was 49.6%, 7.2%, 2.3%, and 2.0%. Individuals with MASLD (adjusted HR [aHR], 1.11), MetALD (aHR, 1.14), ALD with MD (aHR, 1.32) and MASLD with VH (aHR, 1.12) had a higher risk of developing HF compared with the no SLD group. The risk of CV mortality was also increased in those with SLD groups compared to those with no SLD. The risk of new-onset HF and CV mortality showed a J-shaped association with alcohol consumption regardless of SLD status.ConclusionSLD is independent risk factor of new-onset HF and CV mortality in persons with T2DM, and alcohol consumption has a J-shaped association with risk of HF and CV mortality, regardless of SLD status.

Temporal trends in treatment patterns, morbidity, and mortality in patients with new-onset heart failure compared to heart failure survivors: a nationwide 23-year perspective

Abstract Background New therapy options have improved the prognosis of heart failure (HF) over recent decades. However, temporal trends in the prognosis and treatment disparities between patients with new-onset HF and HF survivors remain unexplored. Purpose To investigate temporal trends in HF treatment patterns, worsening HF and all-cause mortality, in new-onset HF patients compared to HF survivors. Methods We defined two separate cohorts of patients with HF, using the Danish nationwide registers. One cohort comprised all patients with new-onset HF each year from 1996 to 2018, included at the date of HF diagnosis (new-onset HF patients). The second cohort comprised patients with HF who have survived at least three years since being diagnosed with HF, included on January 1st of each year from 1996 to 2018 (HF survivors). Patients were allowed to contribute in both cohorts. The proportion of patients in guideline recommended therapy and the absolute five-year risk of worsening HF and all-cause mortality were assessed in the two cohorts separately, accounting for competing risks where relevant. Results From 1996 to 2018, the proportion of HF survivors tripled, while the number of yearly new-onset HF patients remained constant (figure 1). The proportion of new-onset HF patients who redeemed a prescription of BB increased from 17.1% in 1996 to 78.2% in 2018, while it increased from 15.9% to 69.4% in HF survivors during the same period. The proportion of patients in ACEi/ARB therapy increased from 49.1% to 81.5% in the new-onset HF patients, while it increased from 37.8% to 69.0% in HF survivors. The proportion of patients in MRA therapy increased from 14.4 to 33.0% in those with new-onset HF, and from 19.1% to 24.8% in HF survivors. The absolute risk (AR)[±95CI] for all-cause mortality decreased from 68.4% [67.9-68.9] in the first year group (1996-2000) to 45.7% [45.0-46.3] in the latest year group (2013-2018) for new-onset HF patients, while it decreased from 58.4% [58.2-58.9] to 39.7% [39.4-40.0] for the HF survivors. Additionally, the AR for worsening HF went from 27.4% [26.9-27.8] in the first year group to 27.8% [27.3-28.2] in the latest year group for the new-onset HF patients, whereas it for the HF survivors decreased from 19.6% [19.3-20.0] to 16.7% [16.4-19.9]. Conclusions Over a 23-year period, the annual number of patients with incident HF has remained constant while the number of HF survivors has increased by 304%. Although HF survivors show a lower prescription redemption prevalence for essential HF medications compared to incident HF patients, they exhibit significantly lower risk of all-cause mortality and worsening HF.Figure 1:OverviewFigure 2:Prescription redememption rates

Patient characteristics and mortality trends among octogenarians with heart failure over two decades - a Danish nationwide study

Abstract Background Mortality rates among octogenarians with heart failure (HF) have changed little despite significant advancements in care over recent decades. Investigating the factors contributing to this trend may offer valuable insights for devising targeted management strategies for the oldest HF patients. Purpose We aimed to examine different patient characteristics associated with mortality among octogenarians with HF over the past 20 years. Methods From nationwide Danish healthcare registries, we included all patients with new-onset HF between 2001-2020 who were ≥ 80 years old at the time of diagnosis. The patients were categorized into 5-year calendar periods depending on the time of their diagnosis, the first period being between 2001-2005 and the last 2016-2020. The Kaplan-Meier estimator was used to assess the mortality risk. Mortality rates were examined with multivariable Cox regression models, comparing the first (reference) and the last calendar period and adjusting for predefined covariables. Results We included 47,754 octogenarian patients with new-onset HF, of whom 13,293 (51%) were diagnosed between 2001-2005 and 12,813 (49%) between 2016-2020. The distribution of males and females changed between the two calendar periods, with 5696 (43%) males in the first period and 6631 (52%) in the last period. The 3-year absolute mortality risk decreased by 8% [95% CI, 7.9-8.0] from 2001-2005 (64% [95% CI, 63.9-64.7]) to 2016-2020 (56% [95% CI, 55.3-56.7]) (p-value &amp;lt;0.001) (Figure 1). After adjustment for covariables, patients diagnosed in the last period exhibited a mortality hazard ratio (HR) of 0.94 [CI 95% 0.90-0.99] (p-value 0.02) compared to those diagnosed in the first period. An interaction was observed between the first and the last calendar periods among patients with a history of myocardial infarction and those aged &amp;lt;85 years. The survival rates improved over time for patients with a history of myocardial infarction (HR 0.80 [95% CI, 0.72-0.90], p-value for interaction&amp;lt;0.001), as well as for those aged between 80 and 85 years (HR 0.86 [95% CI, 0.80-0.91], p-value for interaction&amp;lt;0.001) (Figure 2). Conclusion Over two decades the mortality risk among octogenarians with HF has improved slightly, however it remains high. Patients with a history of myocardial infarction and those aged 80 to 85 years emerge as subgroups experiencing the most improved survival rates over time.3-year mortality riskMortality rates in selected subgroups

Coexistence of coronary microvascular dysfunction and left ventricular hypertrophy can predict prognosis of patients with nonobstructive coronary arteries

Abstract Background Previous studies have reported that coronary microvascular dysfunction (CMD) and left ventricular hypertrophy (LVH) were associated with adverse cardiovascular events. The aim of this study was to determine the prognostic impact of coexistence of abnormal coronary flow reserve (CFR) and left ventricular mass index (LVMI). Methods and results This study included 297 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery at our hospital from December 2019 to March 2023. Of 297 patients (female: n=89 [30%], age: 70±11 years), 93 (31%) had CMD (CFR&amp;lt;2.5) and 133 (45%) had LVH (LVMI&amp;gt;95 g/m2 for female and &amp;gt;115 g/m2 for male). We excluded patients with history of heart failure (HF). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor LVH, n=109); group 2 (only LVH, n=95); group 3 (only CMD, n=55) and group 4 (both CMD and LVH, n=38). Patients of group 4 had a larger proportion of female (female 19%, 34%, 24% and 61% in group 1 to 4 respectively). There was no significant difference in left ventricular ejection fraction between patients of each groups. Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction and hospitalization for new-onset HF. During a median follow-up of 753 days, the cumulative MACE-free survival rate at 2 year were 99.0%, 98.9%, 95.6% and 90.0% in groups 1 to 4. Group 4 showed significantly higher risk of MACE at 2 year compared with group 1 (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.3-5.3; p=0.009). Notably, Group 4 showed the highest incidence of hospitalization for new-onset HF than any other groups. Conclusion Patients with both CMD and LVH showed significantly higher risk for MACE and new onset of HF. The combined classification based on CFR and LVMI would identify the high-risk patients for MACE as well as new-onset HF.

Temporal trends in mortality and hospitalisation risk in patients with heart failure according to frailty status

Abstract Background Heart failure (HF) and frailty often coexist, and patients with both conditions have a higher risk of mortality and hospitalisation compared with those who are not frail. Over the past two decades, advances in medication targeting HF have been introduced, prolonging the life of patients with HF, but also resulting in increased comorbidity accumulation and susceptibility to frailty. It remains unknown how the interplay between HF and frailty at HF onset impacts patient prognosis and how this has changed over time. Purpose We investigated the temporal trends in the risk of all-cause mortality and HF hospitalisation in patients with HF from 1999 to 2017 according to their frailty status. Methods From Danish nationwide registers, we included patients with new-onset HF. Patients were categorised into four groups according to the year of HF onset: 1999-2002, 2003-2007, 2008-2012, and 2013-2017. The Hospital Frailty Risk Score was used to classify patients into frailty severity categories: 1) non-frail, 2) moderately frail, and 3) severely frail. The primary outcome was the 5-year cumulative incidence of all-cause mortality, assessed using the Kaplan-Meier estimator. The secondary outcome was the 5-year risk of HF hospitalisation, assessed using the Aalen-Johansen estimator, accounting for the competing risk of death. Moreover, a sensitivity analysis was conducted using a multivariable Cox proportional hazard model, investigating the interaction between year group and frailty status for all-cause mortality, comparing frail patients with non-frail patients. Results Among 131,235 patients with HF (median age 74 years; 39.7% female), 102,635 (78%) were categorised as non-frail, 26,054 (20%) as moderately frail, and 2609 (2%) as severely frail. The proportion of moderately frail patients increased the most, from 13% in 1999 to 25% in 2017. From 1999-2002 to 2003-2017, the 5-year cumulative incidence of all-cause mortality declined from 56.4% (95% CI, 55.8-57.0%) to 33.3% (32.6-34.1%), 79.8% (78.5-81.0%) to 58.6% (57.2-60.1%), and 90.8% (85.6-96.0%) to 79.8% (76.4-83.2%) in the non-frail, moderately frail, and severely frail patient group, respectively (Fig 1). The largest relative improvement was observed in the non-frail patient group. The 5-year cumulative incidence of HF hospitalisation remained fairly constant across the frailty groups (Fig 2). Conclusions From 1999 to 2017, we observed an increase in moderately and severely frail patients. Overall, the mortality risk decreased across all frailty groups. These findings underscore the importance of implementing guidelines directed at frail patients with HF.5-year risk of all-cause mortality5-year risk of HF hospitalisation

Temporal trends in clinical outcomes in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018

Abstract Background Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. Purpose We aimed to investigate the temporal trends in all-cause mortality, HF hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and AF. Methods From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were categorised into groups based on their AF status: prevalent AF (n=34,734), new-onset AF (n=12,691), and absence of AF (n=104,634). Patients were further subdivided into four year groups (1997-2001, 2002-2006, 2007-2012, 2013-2018), based on the year of HF onset. The primary outcome of interest was the absolute five-year risk of all-cause mortality, and key secondary outcomes were HF hospitalisation and stroke, investigated using the Aalen-Johansen estimator, accounting for competing risk of death. Results Between 1997 and 2018 the proportion of patients with new-onset HF and prevalent AF increased from 17.0% (n = 6,372) to 27.7% (n = 11,569), while those with concurrent new-onset AF increased from 7.7% (n = 2,884) to 8.1% (n = 3401). Contrary, the proportion of patients decreased among those with no AF from 75.3% (n = 28,235) to 64.2% (n = 26,850). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively (Figure 1). The five-year risk of HF hospitalisation went from 33.3% (32.1%-34.4%) to 30.3% (29.2%-31.4%) in the prevalent AF group, from 25.8% (24.2%-27.4%) to 29.6% (27.7%-31.5%) in the new-onset AF group, and from 28.4% (27.8%-28.9%) to 28.0% (27.2%-28.6%) in the no AF group. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group (Figure 2). Simultaneously, the proportion of patients prescribed anticoagulant therapy within 90 days after HF onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. The five-year risk of mortality and stroke decreased across all patient groups regardless of AF-status. Additionally, prescriptions of anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as patients with HF without AF at the end of the study period.Figure 1 - Mortality in HF patientsFigure 2 - Stroke risk in HF patients

Disparities in clinical characteristics, treatment, and prognosis among immigrants and native patients in Denmark with new-onset heart failure and reduced ejection fraction

Abstract Background Major variations exist in the causes, age at diagnosis, and outcomes of heart failure (HF) in patients from different parts of the world. Purpose To elucidate this issue further, we compared the characteristics and outcomes of immigrants living in Denmark and native Danish patients presenting with new-onset HF with reduced ejection fraction (HFrEF). Methods By linkage of the Danish Heart Failure Registry, and nationwide administrative registries, we identified patients with new onset HFrEF, from 2005-2021, grouped according to immigration status and, if not native Danish, region of origin, according to the World Bank classification. Outcomes were a 1) composite of HF hospitalization or all-cause death at 3 years follow-up, and 2) initiation and up-titration of guidelines-directed medical therapy (GDMT) at 12 months follow-up. Cox regression analyses adjusted for age, sex, calendar year, HF severity, socioeconomic status, and major comorbidities were used to compare the primary composite outcome. Results Of 33,297 patients included, 31,602 (97.9%) were native Danish patients (DK), 1031 (3.1%) were originally from Europe/Central Asia (EUR/CA), 439 (1.3%) from Middle East/North Africa (ME/NAF), 225 (0.7%) from South Asia (SA). The median time since immigration ranged from 20 to 30 years. Compared to DK, patients originating from ME/NAF, and SA were around 10 years younger (median age 62-64 vs. 71 years), had similar median left ventricular ejection fraction (30% vs. 30%), had lower New York Heart Association (NYHA) ≥ class III (14-16% vs. 23%), had more diabetes (39-51% vs. 20%) and ischemic heart disease (IHD) (69-75 vs. 48%), and had less atrial fibrillation (AF) (9-14% vs. 32%) (all p &amp;lt; 0.0001), patients from EUR/CA were generally similar to DK. The crude 3-year cumulative risk of the primary composite outcome was 34% (DK), 31% (EUR/CA), 27% (SA), and 23% (ME/NAF) (Figure 1) In adjusted analyses with DK as the reference, only ME/NAF was associated with a lower risk; hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.62-0.94) (Figure 2). No major differences in the initiation and up-titration of GDMT were observed across groups. Conclusions Non-Western immigrants living in Denmark who presented with new-onset HFrEF had a distinct clinical profile, being generally younger, had lower NYHA class but similar LVEF, a greater prevalence of diabetes and IHD and less AF compared to native Danish patients. In addition, they had lower adjusted rates of the primary outcome of HF hospitalization or all-cause death and a similar likelihood of GDMT initiation and up-titration. The reasons for these differences deserve more research.Figure 1 Crude cumulative riskFigure 2 Adjusted rates

Disparities in SGLT2i utilization among heart failure patients with different ejection fraction in China: findings from chinese cardiovascular association database-heart failure center registry

Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for heart failure (HF) patients regardless of left ventricular ejection fraction (LVEF). Although Chinese HF guidelines still recommend traditional renin–angiotensin–aldosterone system inhibitors, beta blockers, mineralocorticoid receptor antagonists, the Chinese Cardiovascular Association (CCA) HF Center Registry has launched a project to promote the guideline-directed medical therapy (GDMT) for HF patients in China. However, data on the utilization of GDMT in Chinese HF patients is scarce, especially SGLT2i. Purpose We aimed to investigate the usage status of SGLT2i in HF patients with different LVEFs and explore associated factors with SGLT2i adoption in hospitalized HF Chinese patients. Methods This is a retrospective real world study using data from the CCA Database-HF Center Registry. The study included HF patients hospitalized in 52 secondary or tertiary hospitals, including 26 accredited heart failure centers (HFC) and 26 non-accredited heart failure centers (NHFC). Centers that meet the 25 quality control standards established by CCA can be accredited as HFC. We evaluated the use rate of SGLT2i overall and by HF type, as well as the change of SGLT2i usage rate at discharge during the study period from 1st July 2022 to 31st March 2023. LASSO and multivariable logistic regression were also used to explore associated factors of SGLT2i adoption at discharge. Result We included 8,843 hospitalized HF patients: 5,326 (60.2%) were male, 2,980 (33.7%) HFrEF, 1,624 (18.4%) HFmrEF, 3,653 (41.3%) HFpEF and 586 (6.6%) lacked EF data. Overall, SGLT2i were adopted in 3,666 (41.5%) HF patients at discharge (58.1% in HFrEF, 45.3% in HFmrEF, 28.8% in HFpEF). Overall, the usage rate of SGLT2i at discharge rose from 35.2% to 50.2%. Specifically, for HFrEF patients, there was a rise from 56.2% to 64.4%. For HFmrEF and HFpEF patients, the usage rate increased from 37.5% to 54.4% and from 22.2% to 35.7%, respectively (Figure 1). The usage rate of SGLT2i was higher in HFC compared with NHFC (47.1% vs. 35.8%, p&amp;lt;0.001). In multivariable logistic regression, older age, new-onset heart failure, hospital location, etc. were associated with a lower usage rate of SGLT2i at discharge. In contrast, HFC, dilated cardiomyopathy, obesity, etc. were associated with a higher utilization rate of SGLT2i (Figure 2). HF classification by LVEF was also an independent influencing factor even after adjusting other factors; when HFrEF was used as a reference, the use rate of SGLT2i was lower in HFmrEF (OR 0.79, 95% CI 0.69 - 0.91) and HFpEF (OR 0.44, 95% CI 0.39 - 0.49). Conclusion In clinical practice in China, the usage rate of SGLT2i for HF treatment is increasing but needs to be further improved. Disparities exist in usage rates among HF patients with different LVEFs. Addressing this disparity necessitates a targeted approach, emphasizing increased utilization in HF patients regardless of LVEF.SGLT2i usage rate in HFFactors affecting SGLT2i adoption in HF