Risk Of Heart Failure Hospitalization Research Articles

Chest pain and coronary artery disease in cardiac amyloidosis: Prevalence, mechanisms, and clinical implications.

Amyloidosis is a systemic disease affecting multiple organs, and often presents with cardiac involvement, with two primary underlying pathologies: amyloid light chain- and transthyretin cardiac amyloidosis. Chest pain can occur in both types with variable clinical presentations. This narrative review describes the relationship between CA and chest pain. A PubMed search (June 03. 2024) identified 393 articles related to chest pain in CA. Twenty-eight studies, in English and with full text, were selected. Articles included were case reports, reviews, perfusion- and autopsy studies. In CA patients 10-20% report chest pain as the initial symptom preceding the diagnosis, and the overall prevalence of chest pain is 38% of patients with CA and it is related to an increased risk of heart failure hospitalization. The mechanisms leading to chest pain in CA patients include increased left ventricular diastolic pressure, infiltration of amyloid fibrils inside and around coronary arteries, and amyloid compression of the microvasculature. The mechanisms commonly lead to elevations of plasma troponin levels, which are higher in amyloid patients with chest pain compared to amyloid patients without chest pain. Symptomatic treatment of chest pain can be challenging due to the low tolerability of medical therapy and poor outcomes of coronary interventions in alleviating the pain and with a higher rate of complications. Our review underscores the importance of recognizing chest pain as a CA symptom, particularly in the elderly. Persistent troponin elevation without coronary artery disease could indicate CA. Screening-based and longitudinal studies are crucial for understanding the relationship between chest pain and CA. Acknowledging the significance of chest pain in CA may facilitate early intervention and improve patient outcomes.

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 <40%) and HFpEF (EF > 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 4132909: Hemodynamic Indices of Right Ventricular Function Differentially Predict Adverse Clinical Outcomes in Heart Failure with Preserved vs Reduced Ejection Fraction

Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF<50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI <450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p<0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p<0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p<0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.

Abstract 4138553: Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat type 2 diabetes mellitus, but they have also shown benefits in mitigating cardiovascular risk. Given the increasing evidence of their efficacy in diverse disease states and their proposed mechanisms of action, it is plausible that SGLT2i could improve outcomes in patients with acute myocardial infarction (AMI) if administered early after presentation. However, the efficacy and safety of these therapies when used early in the course of acute coronary heart disease remain largely unexplored. Objective: The aim of this current study was to assess the benefit of early initiation of SGLT2i after AMI. Methods: We searched the Cochrane Central Registry of Controlled Trials, PubMed, Embase, Web of Science, and clinicalTrials.gov databases for all randomized controlled trials (RCTs) published up to May 2024 comparing SGLT2 inhibitors to placebo. The primary clinical endpoints included overall mortality, cardiovascular (CV) death, heart failure (HF) hospitalization, and adverse effects. Data were analyzed using a random-effects model to account for potential heterogeneity among the included studies. Significant heterogeneity was defined as an I-squared statistic ≥ 50%; a fixed-effects model was employed if heterogeneity was not significant. The odds ratio (OR) with a 95% confidence interval (CI) was calculated for each endpoint. Results: Four RCTs were included in the analysis, comprising 11,108 patients (SGLT2i, n = 5,561; placebo, n = 5,547) who enrolled with a mean age of 63±9 years and 77% males. SGLT2i were associated with a 28% reduction in risk of HF hospitalization (OR: 0.72 [95% CI, 0.59-0.88]; p = 0.001; I 2 = 0%). However, there was no significant reduction in overall mortality (OR: 1.01 [95% CI, 0.83-1.23]; p = 0.93; I 2 = 27%), CV mortality (OR: 1.04 [95% CI, 0.83-1.30]; p = 0.74; I 2 = 0%), and serious adverse effects (OR: 1.06 [95% CI, 0.87-1.28]; p = 0.59; I 2 = 62%). Conclusion: In patients with AMI, early initiation of SGLT2i was associated with a lower risk of HF hospitalization without increasing the incidence of serious adverse effects when compared to placebo. However, no significant difference was observed in overall mortality and CV deaths.

Abstract 4137695: Bundle Branch Block(BBB) is Independently Associated With Adverse Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejectionfraction(HFPEF): A Propensity Score Matched Analysis

Background: Ventricular dyssynchrony due to BBB can cause adverse cardiovascular(CV) outcomes in HF with reduced EF and is known to occur in HFpEF but its independent impact on is unclear. Objective: To determine if BBB is an independent risk factor for adverse HF outcomes in HFpEF and the impact of atrial fibrillation (AF).. Methods: We studied the impact of BBB in HFpEF utilizing propensity score(PS) matched cohorts without and with BBB from the TOPCAT Americas trial to account for confounding by other co-morbidities. Outcomes analyzed included the TOPCAT primary outcome, CV death&hospitalization (CVH), sudden death, pump failure death (PFD), HF hospitalizations(H), and progression of HF. The impact of concomitant AF ( defined as any AF or AF on ECG) on these outcomes with and without BBB was analyzed. Results: 329 pts with HFpEF&BBB were PS matched for 24 demographic&disease state variables, BNP strata and AF status with a cohort of 329 pts with HFpEF without BBB. BBB was associated with increased risk of the TOPCAT primary outcome (Hazard ratio{HR} 1.44, 95% confidence intervals {CI} 1.10-1.89, p=0.008), increased risk of HF hospitalizations by 41%(HR 1.41 95% CI 1.04-1.91 p=0.0248) but not CVH (HR 1.18, 95% CI 0.93-1.49, p=..169), but not sudden death (HR 1.40, 95% CI 0.70-2.82, p=0.342) or CV death (HR 1.26, 95% CI 0.84-1.89, p=0.257). Risk of pump failure death (PFD) with BBB was significantly higher in HFpEF subjects without a history of AF (Figure left panel .Kaplan Meier Log rank p=0.0478, HR: 4.22, 95% CI: 0.89 to 19.87, p=0.0689) but not in AF (p=0.138). PFD risk was markedly higher in AF subjects without BBB ( Figure right, Kaplan Meier Log rank p=.0012, HR:7.99, 95% CI:1.80 to 35.41,p = 0.0063) than those with BBB (p=0.91) Conclusion: Ventricular dysynchrony induced by BBB independently worsens HFH risk in HFpEF. Its adverse impact on PFD iis seen in the absence of AF. Increase in PFD risk with AF in HFpEF subjects is most prominent in those with normal intraventricular conduction. Mechanical dyssynchrony induced by BBB may have a role in HFpEF subgroups with preserved atrioventricular filling, leading to these adverse HF outcomes

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.

Novel Adiposity Indices Are Associated With Poor Prognosis in Heart Failure With Preserved Ejection Fraction Without the Obesity Paradox.

There is limited study that illuminates the relationship between obesity indices and prognosis in patients with heart failure with preserved ejection fraction, nor has it been examined whether the obesity paradox persists when using these metrics. This study is a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. A total of 3114 individuals were included in our final analysis, and a total of 481 (15.4%) all-cause deaths, and 389 (12.5%) heart failure hospitalizations were recorded. In a multivariable Cox regression model, compared with patients with a body mass index (BMI) <24.9 kg/m2, those with a BMI of 25.0-29.9, 30.0-34.9, and 35-39.9 kg/m2 were associated with a decreased risk of all-cause death, with hazard ratio (95% CI) of 0.59 (0.45-0.78), 0.61 (0.46-0.82), and 0.66 (0.47-0.92), respectively. Conversely, patients with a BMI ≥40 kg/m2 showed an increased risk of heart failure hospitalization, compared with BMI <24.9 kg/m2. Furthermore, patients in the highest quintile of obesity indices exhibited a significantly elevated hazard ratio for both all-cause death and heart failure hospitalization, compared with the lowest quintile. An elevated BMI over a certain range was associated with a reduced risk of all-cause death in heart failure with preserved ejection fraction, displaying a U-shaped relationship, with no mortality reduction observed in cases of extreme obesity. In contrast, higher values of novel obesity indices were positively correlated with all-cause death and heart failure hospitalization without the obesity paradox.

In-hospital bioimpedance-derived total body water predicts short-term cardiovascular mortality and re-hospitalizations in acute decompensated heart failure patients.

Hospital re-admissions in heart failure (HF) patients are mostly caused by an acute exacerbation of their chronic congestion. Bioimpedance analysis (BIA) has emerged as a promising non-invasive method to assess the volume status in HF. However, its correlation with clinically assessed volume status and its prognostic value in the acute intra-hospital setting remains uncertain. In this single-center observational study, patients (n = 49) admitted to the cardiology ward for acute decompensated HF (ADHF) underwent a daily BIA-derived volume status assessment. Median hospital stay was 7 (4-10) days. Twenty patients (40%) reached the composite endpoint of cardiovascular mortality or re-hospitalization for HF over 6months. Patients at discharge displayed improved NYHA class, lower body weight, plasma and blood volume, as well as lower NT-proBNP levels compared to the admission. Compared to patients with total body water (TBW) less than or equal to that predicted by body weight, those with higher relative TBW levels had elevated NT-proBNP and E/e´ (both p < 0.05) at discharge. In the Cox multivariate regression analysis, the BIA-derived delta TBW between admission and discharge showed a 23% risk reduction for each unit increase (HR = 0.776; CI 0.67-0.89; p = 0.0006). In line with this finding, TBW at admission had the highest prediction importance of the combined endpoint for a subgroup of high-risk HF patients (n = 35) in a neural network analysis. In ADHF patients, BIA-derived TBW is associated with the increased risk of HF hospitalization or cardiovascular death over 6months. The role of BIA for prognostic stratification merits further investigation.

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study

Abstract Background Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear. Purpose We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort. Methods Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from &amp;lt;20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF. Results 94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF&amp;gt; 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes. Conclusions A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure

Atrial Fibrillation (AF) detected by repeat handheld ECG screening and the risk of heart failure hospitalization

Abstract Purpose Heart failure and atrial fibrillation (AF) frequently complicate one another. Risk of heart failure in screen-detected patients was not investigated. We aimed to compare risk of hospitalization for heart failure (HHF) between screen-detected and clinically-diagnosed AF, and to evaluate the impact of AF burden. Methods Consecutive patients aged over 65 attending outpatient clinics were prospectively recruited for AF screening, using handheld single-lead ECG (AliveCor) during December 2014 and December 2017. Patients who had &amp;gt;1 visits received repeat screening. All participants were divided into 5 cohorts: (i) previously known AF at enrolment; (ii) initial screen-detected AF; (iii) subsequent screen-detected AF; (iv) clinically-diagnosed AF during follow-up (FU); (v) No AF. Risk of HHF was estimated by adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression, accounting for death as competing risk, adjusting for CHA2DS2VASC components and chronic kidney disease, AF diagnosis being handled as time-dependent variable. Patients who participated in repeat screening and previously known AF formed a sub-cohort. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were defined probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Risk of HHF was compared between groups stratified by AF burden (persistent vs. paroxysmal) and scenario of AF diagnosis (screen-detected vs. clinically-diagnosed). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had known AF, 1.9% (n=223) initial screen-detected AF, 0.6% (n=71) subsequent screen-detected AF, 7.3% (n=867) clinically-diagnosed AF during FU, and 71.6% (n=8,559) no AF. During a median FU of 6.7 (IQR:4.4-8.0) years, risk of HHF was highest in patients with clinically-diagnosed AF (aSHR=3.5(2.7-4.5)), followed by subsequent screen-detected AF (aSHR=2.8(1.6-5.0)), previously known AF (aSHR=1.9(1.6-2.2)), and initial screen-detected AF (aSHR=1.7(1.1-2.4)) (Figure 1a). Sensitivity analysis excluded those with known heart failure at baseline, after which risk of HHF became comparable between previously known and initial screen-detected AF (Figure 1b). Sub-analysis for participants (32.2% (n=3,853), mean age 76.7±7.3, female 47.5%) of repeat screening showed screen-detected persistent AF (aSHR=3.7(1.9-7.2)) was at highest risk of HHF, followed by clinically-diagnosed AF (AF burden unassessed) (aSHR=3.3(2.2-5.0)), previously known persistent AF (aSHR=3.1(2.5-3.8)), screen-detected paroxysmal AF (aSHR=2.1(1.4-3.4)), previously known paroxysmal AF (aSHR=1.8(1.3-2.4) (Figure 1c). Conclusion Higher AF burden and FU new AF diagnosed by either screening or clinic visit was associated with higher risk of HHF. Screening facilitating early AF diagnosis and early downstream intervention, warranted further study.

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

Relationship between chronic obstructive pulmonary disease and heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Chronic heart failure and chronic obstructive pulmonary disease (COPD) are both common diseases and often co-exist. Patients with COPD are at increased risk for hospitalizations due to cardiovascular diseases. However, in patients with atrial fibrillation (AF), the relationship between COPD and the risk of heart failure (HF) hospitalization remains unclear. Purpose The purpose of this study was to investigate the relationship between COPD and HF hospitalization in AF patients. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Japan. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. We compared patients with and without COPD with regard to clinical background and HF hospitalization during follow-up period. Results In this cohort, the proportion of pre-existing HF among patients with COPD was 30.1%, and the proportion of COPD among patients with pre-existing HF was 5.9%. Of 4,496 patients, 238 (5.3%) patients had COPD (COPD; the mean age 75.6 years, female 20.6%), and the remaining 4,258 patients did not (Non-COPD; the mean age 73.5 years, female 41.6%). Patients with COPD were older than those without COPD. However, the proportions of patients with pre-existing HF, previous stroke, vascular disease, cardiomyopathy, coronary artery disease (CAD), diuretic use, renal dysfunction, diabetes mellitus (DM) and hypertension were comparable. During the median follow-up period of 1,824 days, the incidence of HF hospitalization was significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 4.85% vs. 3.01% per person-year: p&amp;lt;0.01). In multivariate analysis adjusted by sex, age (≥ 75 years), heart disease (combined by heart failure, vascular disease, cardiomyopathy and CAD), renal dysfunction, DM, hypertension and diuretic use, COPD was an independent risk factor for HF hospitalization (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.15-2.07, P&amp;lt;0.01) (Figure 1). When we analyzed patients without pre-existing HF, the incidence of HF hospitalization was also significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 2.87% vs. 1.75% per person-year: p=0.02). In multivariate analysis after adjusting for the same factors, COPD was an independent risk factor for HF hospitalization (HR 1.63, 95% CI 1.05-2.53, P=0.03) (Figure 2). Conclusion In patients with AF, COPD was the risk of HF hospitalization. The results were consistent in AF patients without pre-existing HF.

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p&amp;gt;0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Association of cardiac amyloidosis with cardiovascular outcomes after aortic valve replacement in patients with severe aortic stenosis: a systematic review and meta-analysis

Abstract Introduction Aortic stenosis (AS) and cardiac amyloidosis (CA) frequently coexist and is commonly observed in older individuals referred for aortic valve replacement (AVR). However, the association of CA with adverse outcomes after AVR has not been well established. Purpose This meta-analysis aimed to evaluate the association of CA with adverse cardiovascular outcomes in patients with severe AS after undergoing AVR. Methods A literature search was performed for studies evaluating patients with severe AS undergoing AVR, comparing clinical endpoints on follow-up for patients with and without CA. The clinical endpoints included all-cause mortality and heart failure (HF) hospitalization. Databases searched included Ovid MEDLINE, Embase, and Web of Science. Subgroup analysis was performed for short term (&amp;lt;30 days) and long term (&amp;gt;30 days) mortality. The search was not restricted to time or publication status. Results Five studies including 1,105 patients with severe AS (111 with concurrent CA, 904 without CA) met inclusion criteria. The mean follow-up duration was 24.6 months, mean age was 81.2 years and 55.4% were men. Mean echocardiographic aortic valve parameters included valve area of 0.715cm2, mean gradient of 41.8 mmHg, and peak velocity of 4.2m/s. The mean left ventricular ejection fraction was 58%. All except 1 study included only patients with ATTR CA while excluding other causes of CA. There was no statistically significant difference in all-cause mortality between patients with and without CA following AVR, both in short-term (OR 0.94; 95% CI 0.17-5.31; p=0.95) and long-term (OR 1.72; 95% CI 0.75-3.91; p=0.20) follow-up. However, patients without CA demonstrated a significantly lower risk of heart failure hospitalization post-AVR compared to those with CA (OR 2.49; 95% CI 1.18–5.23; p = 0.02). Conclusion In the context of patients with severe AS undergoing AVR, the presence of CA does not appear to significantly impact short-term or long-term all-cause mortality. Notably, patients without CA exhibited a lower risk of heart failure hospitalization following AVR. These findings underscore the importance of considering cardiac amyloidosis in the clinical management of severe AS and highlight potential differences in outcomes based on its presence or absence. Additional studies are needed to elucidate outcome differences for CA patients who undergo surgical versus transcatheter AVR.Figure 1

Left ventricular ejection fraction and clinical outcomes after transcatheter aortic valve implantation

Abstract Background Reduced left ventricular ejection fraction (LVEF ≤50%) has been associated with poor prognosis in patients with severe aortic stenosis treated medically or with aortic valve replacement. However, less is known regarding the impact of different degrees of LVEF including moderately to severely reduced LVEF after transcatheter aortic valve replacement (TAVR). Purpose To examine the association between baseline LVEF and clinical outcomes after TAVR. Methods Patients undergoing TAVR between 2008-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. LVEF was estimated from echocardiography before TAVR and categorized as ≥50%, 40-49%, 30-39% and &amp;lt;30%. SWENTRY was linked to the National Patient Registry and Cause of Death Registry for outcome variables. Patients were followed for a median of 3.2 years for the primary outcome heart failure hospitalizations and the secondary outcome all-cause mortality. Cox regression analyses adjusted for age, sex, BMI, atrial fibrillation, eGFR class, diabetes, hypertension, frailty, chronic pulmonary disease and coronary artery disease were performed for the association between LVEF groups and outcome. Results In total, 8686 patients were included (mean age 81 years, 47% female) of whom 5904 (68%) patients had LVEF ≥50%, 1342 (15%) had LVEF 40-49%, 906 (10%) had LVEF 30-39% and 534 (6%) had LVEF &amp;lt;30%. Significant differences were observed across the LVEF groups in the cumulative incidence rates of heart failure hospitalizations (19, 30, 37 and 43%; p&amp;lt;0.001) and all-cause mortality (41, 54, 55, 57%; p&amp;lt;0.001) at five years. In adjusted analyses there was a stepwise increase in the risks of heart failure hospitalizations (Figure 1A) and all-cause mortality (Figure 1B) for each respective LVEF category. Conclusion Reduced LVEF, especially LVEF &amp;lt;30%, was associated with a dramatically increased long-term risk of heart failure hospitalizations and all-cause mortality in patients undergoing TAVR. LVEF should be considered in risk stratification and patient selection for TAVR.

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (&amp;lt;25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value &amp;lt;0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI &amp;lt;25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI &amp;lt;25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI &amp;lt;25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Periprocedural changes in systolic pulmonary artery pressure in transcatheter aortic valve implantation

Abstract Background Pulmonary hypertension (PH) is common in patients with aortic stenosis and associated with increased mortality following transcatheter aortic valve replacement (TAVR). PH often improves after TAVR and systolic pulmonary artery pressure (sPAP) can change, but to what extent these changes in sPAP following TAVR affect long-term prognosis is unclear. Purpose To investigate the association between periprocedural changes in sPAP and long-term prognosis after TAVR. Methods Patients undergoing TAVR between 2012-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. sPAP was estimated from echocardiography before and after TAVR and categorized as: (1) No PH before and unchanged (≤5 mmHg change) after, (2) No PH before and worsened (&amp;gt;5 mmHg increase) after, (3) PH before and improved (&amp;gt;5 mmHg decrease) after, (4) PH before and unchanged after and (5) PH before and worsened after. An sPAP cutoff at &amp;gt;50 mmHg was applied for PH. Patients were followed for a median of 3.1 years for the primary endpoint heart failure hospitalizations (HFH) and the secondary endpoint all-cause mortality. Cox regression analyses were performed and adjusted for age, sex, body mass index, atrial fibrillation, eGFR class, diabetes, frailty, left ventricular ejection fraction and chronic obstructive pulmonary disease. Results In total, 4926 patients were included (mean age 82 years, 50% female) among whom 2596 (53%) patients had no PH and unchanged, 864 (18%) had no PH and worsened after, 912 (19%) had PH and improved after, 401 (8%) had PH and unchanged after and 153 (3%) had PH and worsened after. The mean sPAP levels preoperatively in each group were 36, 31, 60, 58, 57 mmHg respectively. Mean change in patients with no PH and worsened was +16 mmHg, in patients with PH and improved -20 mmHg and in patients with PH and worsened +14 mmHg. Cumulative incidence rates of HFH at 5 years among the five groups were 18%, 25%, 32%, 41%, and 52%, respectively (p&amp;lt;0.001). In adjusted analyses, there was a stepwise increase in the risk of HFH (Figure 1A) and all-cause mortality (Figure 1B) for no PH and worsened, PH and improved, PH and unchanged and PH and worsened as compared with no PH and unchanged. Conclusion Increase of periprocedural sPAP in patients with and without known PH before TAVR was associated with worse prognosis whereas reduction of sPAP was associated with improved outcomes.

Amiodarone-related thyroid dysfunction and associated outcomes in patients with heart failure - a matched case-control study

Abstract Aim The association between amiodarone-related thyroid dysfunction and the risk of worsening heart failure (HF) or death has been reported with conflicting results. Methods The study cohort was patients with HF and without a history of thyroid dysfunction (defined by medical treatment or diagnosis) who initiated treatment with amiodarone in the period 1996-2021. Within this cohort, those who developed thyroid dysfunction (cases) were identified and matched 1:3 on age, sex, calendar year, duration of HF, and time since initiation of amiodarone with patients (controls) from the same cohort and followed for the primary outcome of HF hospitalization or all-cause death at 1-year, assessed by Kaplan Meier curves and Cox regression models adjusted for ischemic heart disease, chronic kidney disease, malignancy, atrial fibrillation and ventricular tachycardia. Results The study cohort comprised 21,947 patients, of whom 4,137 (19%) developed thyroid dysfunction following initiation of amiodarone. After matching, the study population consisted of 4,063 cases (mean age 69 years, 68% men, 41.6% developed thyroid dysfunction within the first year after initiation of amiodarone) and 10,940 matched controls, (Figure 1). The index date was the date of thyroid dysfunction for cases, and for matched controls a date at a similar distance since amiodarone initiation. At 1-year follow-up, the primary outcome occurred in 1,543 (38.0%) cases and 3,681 (33.6%) matched controls (reference), adjusted hazard ratio (HR) 1.13 (95%, confidence interval CI 1.07-1.20), although this was solely driven by HF hospitalization (28.9% vs 21.8%; HR 1.32 (95% CI 1.23-1.41), whereas all-cause death was lower among cases (18.2% vs. 20.4%, HR 0.85 (95% CI 0.78-0.93), (Figure 2). Conclusions Among HF patients treated with amiodarone, the development of thyroid dysfunction was associated with an increased risk of HF hospitalization or all-cause death, but this was solely driven by the excess risk of HF hospitalization, whereas it was associated with a lower risk of all-cause death. The absence of excess mortality indicates that thyroid complications are manageable in this vulnerable population of patients with HF.Figure 1 Flowchart of the populationFigure 2 Cumulative risk

Long-term clinical course of heart failure across left ventricular ejection fraction phenotypes

Abstract Background Studies examining changes in cardiac features and long-term outcomes across heart failure (HF) phenotypes, particularly for normal and supranormal left ventricular ejection fraction (LVEF), are limited. Objectives Our objective was to assess changes in echocardiographic parameters and biomarkers over three years and investigate long-term outcomes across LVEF phenotypes in chronic HF. Methods Patients from the SUPPORT trial (mean age 66 years, 25% female, mean LVEF 54%), a prospective, randomized, open-label blinded endpoint study performed in Japan to determine the additional benefit of olmesartan on top of standard therapy in hypertensive patients with HF, were classified into four HF phenotypes based on baseline LVEF: reduced (HFrEF [LVEF ≤40%], n=200 [17.6%]), mildly reduced (HFmrEF [41% ≤ LVEF &amp;lt;50%], n=229 [20.1%]), normal (HFnEF [51% ≤ LVEF &amp;lt;65%], n=403 [35.4%]), and supranormal (HFsnEF [LVEF ≥65%], n=306 [26.9%]). Changes in echocardiographic parameters and biomarkers were assessed in patients with data available at baseline and three years. The composite outcome of HF hospitalization or all-cause death was analysed from baseline and three years (landmark analysis). Results Over three years, all-cause mortality rates were 15% in HFrEF, 10.0% in HFmrEF, 5.5% in HFnEF, and 4.2% in HFsnEF. The most significant decrease in left ventricular (LV) end-diastolic and -systolic diameter occurred in HFrEF (median percent change; LVDd -5.8% and LVDs -8.8%). Left atrial diameter did not change across HF phenotypes. N-terminal pro-brain natriuretic peptide (NT-proBNP) decreased in HFrEF (-35.7%) but increased in HFnEF and HFsnEF (12.5% and 18.2%, respectively). Troponin increased in all groups except for HFrEF. Growth differentiating factor-15 (GDF15) increased consistently across all HF phenotypes (18.5% in HFrEF, 18.0% in HFmrEF, 16.0% in HFnEF, 22.8% in HFsnEF) (Figure 1). Over a median follow-up of 8.6 years, compared to HFnEF, the risk of the composite outcome was higher in HFrEF (adjusted HR 1.40, 95% CI [1.08-1.82]), but was not different in HFmrEF (1.15, [0.90-1.47]). This trend persisted in the landmark analysis. Up to three years, the risk in HFsnEF compared to HFnEF was not different (1.13, [0.70-1.82]), but it was lower after three years (0.73, [0.55-0.95]). The incident curves show a diverging time point at around three years between HFnEF and HFsnEF (Figure 2). Conclusions In patients with chronic HF and three-year follow-up data, there was minimal decrease in LV dimension, most pronounced in HFrEF. Changes in biomarkers were more diverse, except for consistently elevated GDF15 across all HF phenotypes. The risk of HF hospitalization or all-cause death diverged between HFnEF and HFsnEF after three years.Figure 1Figure 2