Baseline Heart Failure Research Articles

Association between dietary intake of iron and heart failure among American adults: data from NHANES 2009–2018

Patients with heart failure (HF) often experience iron deficiency. Intravenous iron supplementation has been widely used in clinical practice to facilitate the treatment of HF. However, the association between dietary iron intake and HF still needs to be elucidated. This study aimed to evaluate the impact of dietary iron intake on HF in American adults. The data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2009–2018. Iron dietary intake data were obtained from two 24-h dietary recall interviews. We examined baseline data and HF prevalence in different quartile groups of dietary iron intake (Q1–Q4). Two logistic regression models were established to evaluate the impact of Q4 (highest iron consumption) on the risk of HF. The study included 20,853 American adults (age ≥ 20 years). The participants with the highest iron intake (Q4) had the lowest prevalence of HF (Q1: 3.25%, Q2: 2.18%, Q3: 1.92%, Q4: 1.72%; P < 0.001). After adjusting for possible confounding factors, the highest iron intake (Q4) was significantly associated with a reduced risk of HF compared with that of Q1 (odds ratio 0.58, 95% confidence interval 0.41–0.82; P = 0.003). This association remained stable in subgroups of women, current smokers, and Hispanics other than Mexican Americans. This study revealed that the dietary intake of iron was negatively associated with HF in adults without exceeding the tolerable maximum daily intake of 45 mg/day.

Long-Term Cardiovascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a promising class of medications for type 2 diabetes (T2D) management. While their glucose-lowering effects are well-established, their long-term impact on cardiovascular outcomes remains a subject of ongoing research and debate. This systematic review aims to assess the long-term cardiovascular effects of GLP-1 RAs in adults with T2D compared to placebo, standard care, or other glucose-lowering medications. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies published from database inception to April 2024. Two independent reviewers screened the studies and extracted the data. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Secondary outcomes included individual components of MACE, hospitalization for heart failure, and all-cause mortality. We included 15 studies (eight RCTs and seven observational studies) involving over 180,000 participants. GLP-1 RAs were associated with a significant reduction in MACE compared to placebo or standard care (risk ratio: 0.88, 95% CI: 0.82-0.94, p<0.001). GLP-1 RAs also demonstrated superior cardiovascular protection compared to DPP-4 inhibitors and sulfonylureas. The benefits were particularly pronounced in reducing the risk of stroke and MI. Notably, some studies found larger cardiovascular benefits in frail patients. The effects on heart failure outcomes were mixed, with potential attenuated benefits in patients with baseline heart failure. GLP-1 RAs also showed promising effects on renal outcomes and metabolic parameters. The quality of evidence ranged from moderate to high across outcomes. This systematic review provides strong evidence that GLP-1 RAs offer significant cardiovascular benefits in adults with T2D, particularly in reducing MACE, stroke, and MI. The findings support current guidelines recommending GLP-1 RAs as preferred agents in patients with established cardiovascular disease or high cardiovascular risk. However, the variability in effects across different patient subgroups underscores the need for personalized treatment approaches. Future research should focus on head-to-head comparisons between different GLP-1 RAs, long-term follow-up studies, and investigation of combination therapies to further optimize the use of these agents in clinical practice.

A liberal blood transfusion strategy is safe in patients with myocardial infarction, anemia, and heart failure: lessons from MINT

Abstract Background In patients with acute myocardial infarction (MI) and anemia, the Myocardial Ischemia and Transfusion (MINT) trial found a trend toward increased 30-day death or recurrent MI with a restrictive compared with a liberal blood transfusion strategy. Patients with and without heart failure (HF) may respond differently to blood transfusion. Purpose To characterize the effects of restrictive vs. liberal transfusion strategies on clinical outcomes in patients with MI and anemia with and without baseline HF. Methods In the MINT trial, 3504 patients with MI and hemoglobin &amp;lt;10 g/dL were randomized to restrictive (7-8 g/dL) or liberal (10 g/dL) transfusion thresholds. We compared outcomes between patients with and without baseline HF, defined as any history of HF, acute HF, or baseline left ventricular ejection fraction (LVEF) &amp;lt;45%. Outcomes included death or incident HF, death or recurrent MI, death, and incident HF, all at 30 days. Results Compared with patients without baseline HF (n=1633), patients with baseline HF (overall n=1871 (history of HF n=1066, acute HF n=780, LVEF &amp;lt;45% n= 1099) were older, more frequently male and Black, and had higher rates of prior PCI, diabetes, and hypertension. In the restrictive strategy, patients with and without baseline HF received an average of 0.63 and 0.80 units of blood and had a median LOS of 6 and 4 days, respectively. In the liberal strategy, patients with and without baseline HF received an average of 2.44 and 2.49 units of blood and had a median LOS of 5 and 4 days, respectively. Patients with baseline HF had higher rates of death or incident HF (18.0% vs. 10.0%, risk ratio [RR]=1.79 [95% confidence interval {CI} 1.50-2.13]), death or recurrent MI (17.6% vs. 13.5%, RR=1.31 [95% CI 1.12-1.53]), and death (10.5% vs. 7.5%, RR 1.41 [95% CI 1.14-1.75]). Among patients with baseline HF, a restrictive transfusion strategy resulted in a trend toward an increase in death or HF and death or MI compared with a liberal transfusion strategy (Table, Figure). Among patients without baseline HF, the risk of incident HF was lower with restrictive than with liberal transfusion strategy. Conclusions Among patients with MI and anemia, a restrictive transfusion strategy resulted in a greater increase in death or HF, death or MI, and death in patients with baseline HF than in patients without baseline HF. A liberal transfusion strategy is safe for patients with MI and anemia, including those with prior or acute HF.TableFigure

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF &amp;lt; 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

Quality of life in patients with heart failure and improved ejection fraction: one-year follow-up with ARNI and SGLT2i

Abstract Introduction A baseline Heart Failure (HF) with reduced Ejection fraction (HFrEF) &amp;lt;=40% that improved for &amp;gt;=10 points and a second measured left ventricle ejection fraction (LVEF) &amp;gt;40%, can be considered as HF with improved ejection fraction (HFimpEF). The novel therapy for HFrEF and HFimpEF are sacubitril/valsartan (ARNI- angiotensin receptor/neprilysin inhibitor) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i). Purpose Our study aimed to evaluate ARNI and SGLT2i therapy on the health status of HFrEF patients, as well as the prognostic impact of HFimpEF in terms of quality of life and outcomes (mortality and rehospitalization due to HF) during a one-year follow-up. Methods In this prospective study, we included 376 hospitalized HFrEF patients, in whom ARNI and SGLT2i were initiated into regular therapy. A 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was performed at discharge and after one year. The primary prognostic endpoints were all-cause mortality and HF rehospitalization. Results Initially, about two-thirds of the study population were men (71%), mean age of 61.0±11.5 years, mean LVEF 27.5±5.2 % and mean KCCQ overall summary (KCCQ-OS) score of 48.5±12.5, while quality of life KCCQ-QoL 37.4±10.2. After one year LVEF was increased by 35.6±7.1 %. The total number of 143 patients (38%) met the criteria for HFimpEF, with the improvement of mean LVEF (45.2±8.6 %., p&amp;lt;0.001). Overall, HFimpEF patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS compared with 2.5 ± 17.4 points for non-HFimpEF group (differences in mean changes of 2.9 [95% CI: 1.4 to 4.7). This is largely due to improvements in the domain of KCCQ-QoL (5.8 ± 29.7 points vs. 2.9 ± 22.2 points, respectively). During one year of follow-up, combined SGLT2i + ARNI therapy was represented statistically significantly more in HFimpEF compared to the non-HFimpEF group (86% vs. 34%, p&amp;lt;0.0005), where 45% took only one medicine and 21% none. The HFimpEF group had a significantly better outcome in terms of all-cause mortality (2.8% vs. 18.9%, p&amp;lt;0.005) and HF rehospitalization (3.5% vs. 40%, p&amp;lt;0.0001). The one-year KCCQ-12 was independently associated with outcomes; the hazard ratio for the integrated endpoints (mortality and HF rehospitalization) was 1.08 (95% CI: 1.05–1.11, p = 0.005). Conclusions In routine clinical practice, initiation of the ARNI and SGLT2i therapy was associated with significant improvements in the health status of HFrEF patients, but also change to HFimpEF. The one-year quality of life in patients with heart failure and improved ejection fraction was superior to baseline and compared to the non-HFimpEF group. HFimpEF was associated with a better outcome. All HF patients should undergo KCCQ-12 because it is an independent predictor of outcome.

A multiparametric heart failure score at baseline is associated with long-term outcome in patients with remotely monitored implantable cardioverter-defibrillators: A pooled analysis of 9 clinical trials

BackgroundTo predict worsening heart failure hospitalizations (WHFHs), the HeartInsight multiparametric algorithm calculates a heart failure (HF) Score based on temporal trends of physiologic parameters obtained through automatic daily remote monitoring of implantable cardioverter-defibrillators (ICDs). ObjectiveWe studied the association of the baseline HF Score, determined at algorithm activation, with long-term patient outcomes. MethodsData from 9 clinical trials were pooled, including 1841 ICD patients with a preimplantation ejection fraction ≤35%, New York Heart Association class II/III, and no long-standing atrial fibrillation. The primary end point was a composite of death or WHFH. ResultsAfter a median follow-up of 631 days (interquartile range, 385–865 days), there were 243 WHFHs in 173 patients (9.4%) and 122 deaths (6.6%), 52 of which (42.6%) were cardiovascular. The primary end point occurred in 265 patients (14.4%). A multivariable time-to-first-event analysis showed that a high baseline HF Score (>23, as determined by a time-dependent receiver operating characteristics curve analysis) was significantly associated with the occurrence of the primary end point (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.54–2.71; P < .0001), all-cause death (HR, 2.37; CI, 1.56–3.58; P < .0001), cardiovascular death (HR, 2.19; CI, 1.14–4.22; P = .019), and WHFH (HR, 1.91; CI, 1.35–2.71; P = .0003). In a hierarchical event analysis of all-cause death as the outcome with highest priority and WHFHs as repeated event outcomes, the win ratio was 2.47 (CI, 1.89–3.24; P < .0001). ConclusionBased on a retrospective analysis of clinical trial data with adjudicated events, baseline HF Score derived from device-monitored variables was able to stratify patients at higher long-term risk of death or WHFH.

Prevalence and incidence of heart failure in type 2 diabetes patients: results from a nationwide prospective cohort—the DIABET-IC study

BackgroundType 2 diabetes (T2D) patients have an increased risk of heart failure (HF). There are limited data on the association between HF and T2D in specific healthcare settings. This study sought to analyse the prevalence and incidence of HF in a contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics.MethodsWe conducted an observational multicentre prospective study (DIABET-IC) that enrolled patients with a T2D diagnosis attending cardiology and endocrinology outpatient clinics in 30 centres in Spain between 2018 and 2019. The prevalence at the start of the study and the incidence of HF after a 3 year follow-up were calculated. HF was defined as the presence of typical symptoms and either: a) LVEF < 40%; or b) LVEF ≥ 40% with elevated natriuretic peptides and echocardiographic abnormalities.ResultsA total of 1249 T2D patients were included in the present analysis (67.6 ± 10.1 years, 31.7% female). HF was present in 490 participants at baseline (prevalence 39.2%), 150 (30.6%) of whom had a preserved ejection fraction. The presence of adverse social determinants and chronic conditions such as chronic kidney disease and atherosclerotic cardiovascular disease were more frequent in HF patients. During the study period, there were 58 new diagnoses of HF (incidence 7.6%) among those without baseline HF. The incidence rate was 3.0 per 100 person-years. Independent predictors of incident HF were smoking, left ventricular ejection fraction, NT-ProBNP, history of tachyarrhythmia and treatment with pioglitazone, oral anticoagulants, or diuretics. Despite an average suboptimal glycaemic control, the use of antidiabetic drugs with cardiovascular benefits was low (30.4% for sodium-glucose cotransporter-2 inhibitors and 12.5% for glucagon-like peptide-1 receptor agonists).ConclusionsIn this contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics, the prevalence and incidence of HF were high, comorbidities were frequent, and the use of antidiabetic agents with cardiovascular benefit was low. Outpatient care seems to be a unique opportunity for a comprehensive T2D approach that encompasses HF prevention, diagnosis, and treatment.Graphical

Titration of Medications After Acute Heart Failure Is Safe, Tolerated, and Effective Regardless of Risk

BackgroundGuideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. ObjectivesThe authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score. MethodsIn STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. ResultsAmong 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant). ConclusionsHIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

Effectiveness and safety of empagliflozin: final results from the EMPRISE study.

Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases. We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure. We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events. Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

Heart failure during acute coronary syndrome and the long-term cancer risk: the ABC-9 Study on heart disease.

A higher risk of cancer among patients with heart failure (HF) has been suggested in recent community-based studies. This study aimed to investigate the impact of HF during hospitalization with acute coronary syndrome (ACS) on the long-term cancer risk. The study included 572 patients admitted with ACS to three Italian hospitals, discharged cancer-free, and prospectively followed for 24years or until death. All but three patients completed the follow-up, which represented 6440 person-years (mean age: 66±12years; 70% males). Baseline HF was diagnosed in 192 (34%) patients. A total of 129 (23%) patients developed cancer (103 without HF and 26 with HF), and 107 (19%) patients died due to it (81 without HF and 26 with HF). The incidence rates for cancer onset and cancer death were not different according to HF status. Cox regression analysis revealed no association between HF or left ventricular ejection fraction (LVEF) and cancer risk. In addition, no difference in cancer risk was observed among patients with HF with preserved ejection fraction, HF with mildly reduced ejection fraction, and HF with reduced ejection fraction. In competing risk regression analysis, the risk of cancer onset associated with HF was sub-hazard ratio (SHR) 0.47 [95% confidence interval (CI): 0.30-0.72; P=0.001] and SHR 1.02 (95% CI: 1.01-1.04; P=0.002) with LVEF. Results were the same in the adjusted model. Yet the fully adjusted model showed an attenuated association between cancer death and HF (SHR: 0.63; 95% CI: 0.37-1.05; P=0.08) and LVEF (SHR: 1.02; 95% CI: 0.99-1.06; P=0.08). Consistent results were obtained after using propensity score matching analysis that created 192 pairs. A negative interaction between age and HF and a positive interaction between age and LVEF for cancer risk have also been found. An inverse association between baseline HF and long-term cancer risk has been observed among the ABC Study on heart disease patients who were followed for 24years after ACS.

Optimal management to prevent acute kidney injury in patients with acute coronary syndrome in the opinion of physicians from cardiology, nephrology and internal medicine departments – a multicentre survey study

Introduction and objective: Multivessel coronary artery disease affects approximately 50% of patients with acute coronary syndrome. Revascularisation should not only address the culprit lesion, but should include other significant coronary stenoses. The currently accepted approach involves performing a second angioplasty during hospitalisation due to acute coronary syndrome. The time that should elapse between two stages has not been established, and the concern about deterioration of renal function is a common reason for postponing the second angioplasty. The purpose of this study was to find out doctors’ opinions on the optimal management to prevent kidney injury in patients undergoing two-stage revascularisation. Materials and methods: The study was conducted in the form of an anonymous online survey. It was attended by 84 physicians from 6 centres offering invasive treatment of acute coronary syndromes. The questionnaire included 3 questions characterising respondents and 6 questions on kidney injury. Results: Physicians’ opinions varied, both on the main risk factors for acute kidney injury and on the optimal timing of the second percutaneous coronary intervention. The most frequently mentioned factors responsible for kidney injury included: baseline kidney dysfunction, hypoperfusion and heart failure. Almost half of the respondents believed that more than 48 hours should elapse between the two stages of revascularisation. Conclusions: Our study indicates the lack of standards for the management in patients with acute coronary syndrome qualified for staged revascularisation. Further studies are needed to determine the optimal timing of the second stage of angioplasty.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome

Abstract Background Cardiac time intervals are sensitive markers of myocardial dysfunction that predisposes to heart failure (HF). Color tissue Doppler imaging (TDI) curved M-mode is a reliable method for measuring cardiac time intervals. Purpose We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS). Methods This was a retrospective cohort study of 580 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination performed a median of two days after PCI. By echocardiography cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI curved M-mode and used to derive the myocardial performance index (MPI). The outcome was incident HF. Patients with prevalent at baseline HF were excluded from the analysis. Results The final study sample consisted of 387 patients, 73% were male, the mean age was 64 years, 76% of the ACS events were STEMI and LVEF and GLS were 42% and -13.1%, respectively. During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, longer combined indexes were associated with a higher risk of HF (IVRT/ET: HR 1.24 (1.07-1.43), P = 0.003, per 0.1 increase) and (IVCT/ET: HR 1.44 (1.10-1.91), P = 0.010, per 0.1 increase), and so was higher MPI (HR 1.20 (1.08-1.34),P = 0.001, per 0.1 increase). In addition, shorter ET was also associated with higher HF risk (HR 1.13 (1.07-1.18), P&amp;lt;0.001 per 10ms decrease). MPI and IVCT/ET showed a curvilinear association with the outcome, whereas a linear association was observed for ET and IVRT/ET to the outcome (figure 1). After multivariable adjustment for cardiovascular risk factors, only MPI (HR 1.13 (1.01-1.27), P = 0.034), ET (HR 1.09 (1.01-1.17), P = 0.025), and IVCT/ET (HR1.37 (1.04-1.81), P = 0.023) remained significantly associated with HF. Of note, left ventricular ejection fraction (LVEF) significantly modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF even in those with preserved LVEF (&amp;gt;40%) (HR 1.13 (1.02-1.24, P = 0.017, per 10ms decrease), but not in those with reduced LVEF (HR 1.02 (0.96-1.08), P = 0.56, per 10ms decrease). These findings also persisted after adjustment for cardiovascular risk factors. Conclusion Shortened ET, prolongation of combined indexes, and higher MPI were associated with an increased risk of incident HF. In addition, shortening of the ET was associated with an increased risk of HF in patients with preserved systolic function by LVEF.

Estimating the extent to which chronic kidney disease mediates the association between metabolic syndrome and heart failure: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background/Introduction Metabolic Syndrome (MetS) is linked to increased risk of developing heart failure (HF), underscoring a need to implement more aggressive lifestyle and pharmacotherapeutic HF prevention strategies. Chronic kidney disease (CKD) is associated with MetS and is a risk factor for HF; however, therapies protective against both kidney function decline and HF risk such as ACEi/ARBs and SGLT2i are underutilized among individuals with MetS. A potential contributor to this underutilization is that creatinine (Cr)- based estimates of glomerular filtration rate (eGFR) may underestimate the role of CKD as a mediator of HF risk relative to Cystatin-C (CysC) based eGFR. Purpose To compare estimations of the relationship between MetS and kidney function, and of the extent to which eGFR mediates the link between MetS and incident HF, using CysC-based versus Cr-based eGFR. Methods Among ARIC Visit 4 (1996-1998) participants without baseline HF, we used linear regression to assess the cross-sectional association of MetS severity (measured using an established z-score, modeled in quartiles and continuously) with eGFR, with comparisons across 3 different eGFR equations (CKD-Cr 2021, CKD-Cr-CysC 2021 and CKD-CysC 2012). In prospective analyses, we used Cox regression and mediation analyses to estimate the extent to which kidney function mediated the association between MetS and incident HF after Visit 4 through 12/31/2019, with comparisons across the 3 eGFR equations. Results Among 8,582 participants (mean age 63.1 years, 56.9% women, 18.4% Black adults), 1,803 developed HF over a median follow-up of 21 years. MetS was more strongly associated with eGFR when using eGFR estimates that included CysC, with the 4th vs 1st quartile of MetS Z-score associated with an adjusted eGFR difference of -2.55 ml/min/1.73m2 (95% CI -3.36 to -1.73) for CKD-Cr, -8.07 ml/min/1.73m2 (95% CI -8.95 to -7.19) for CKD-Cr-CysC and -10.74 ml/min/1.73m2 (95% CI -11.67 to -9.80) for CKD-CysC. In prospective analyses, we also estimated greater mediation by kidney function of the association between MetS and incident HF when using eGFR equations that included CysC. The strength of the association between MetS and HF potentially mediated by kidney function increased from 3.0% to 15.2% to 24.2%, respectively, when using eGFR-Cr vs eGFR-Cr-CysC vs eGFR-CysC (Table and Figure). These estimates were not significantly attenuated after additional adjustment for coronary heart disease and C-reactive protein. Conclusion(s) The degree of kidney function reduction associated with MetS, and the subsequent implications of kidney dysfunction for HF risk in those with MetS, are underestimated using eGFR-Cr equations compared to eGFR equations including CysC. Greater appreciation by clinicians of the impact of kidney disease on HF risk among individuals with MetS could help increase utilization of kidney-protective therapies that can lower HF risk.

Abstract 14614: Effect of SGLT2 Inhibitors on Renal Outcomes Across Various Patient Populations

Background: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on renal outcomes in patients with varying combinations of heart failure (HF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) remains unclear. Methods: Online databases were queried up to May 2023 for primary and secondary analysis of trials of SGLT2i in patients with HF, CKD, or T2DM. Outcomes of interest were composite renal endpoint (defined as an eGFR &lt;15 mL/min/1.73 m2, doubling of serum creatinine, some percent change in eGFR, and/or need for kidney replacement therapy) and change in estimated glomerular filtration rate (eGFR) slope. Hazard ratios (HR) and mean difference with their 95% confidence intervals were pooled using the generic inverse variance method and a random-effects model. Results: 10 trials (n=70,117 patients) were included. Compared with placebo, SGLT2i reduced the risk of composite renal endpoint by 35% in HF (HR: 0.65; 95% CI: 0.50-0.84), 38% in CKD (HR: 0.62; 95% CI: 0.54-0.71), and 37% in DM (HR:0.63; 95% CI: 0.54, 0.73). A similar pattern of benefit was observed in different combinations of these diseases ( Figure 1 ), as well as patients without baseline HF (HR:0.57; 95% CI: 0.51, 0.63), CKD (HR:0.64; 95% CI: 0.42, 0.98) and T2DM (HR:0.62; 95% CI: 0.45, 0.86). Findings were similar for change in eGFR slope. Conclusions: SGLT2i improve renal outcomes in cohorts of HF, CKD and T2DM and these effects appear consistent across patients with different combinations of these conditions.

Abstract 14705: Diastolic Function is Uniquely Augmented by Direct Mechanical Ventricular Actuation in the Failing Heart

Introduction: Diastolic dysfunction represents a significant pathophysiology in cardiomyopathies and heart failure (HF), yet limited therapies exist for treatment. Direct Mechanical Ventricular Actuation (DMVA) is a non-blood contacting device highly unique in its ability to provide both diastolic and systolic support. The purpose of this study was to further evaluate DMVA’s effect on diastolic function in the failing heart. Methods: Adult canine (63.7 ± 13.4 lb, n=9) underwent repeated cycles of ventricular fibrillation to generate progressive levels of acute HF. DMVA was applied to support HF after defibrillation. Intracardiac echocardiography was used to quantify LV longitudinal strain/strain rates using speckle-tracking algorithms. Strain/strain rate peak magnitudes and composite waveforms were analyzed during baseline (n = 35), DMVA (n = 127), and non-support HF (n = 127). One-way ANOVA with post-hoc Tukey’s HSD was used to assess statistical differences (p&lt;0.05) for all comparisons. Results: LV strain metrics were augmented during DMVA support (strain: 20.0 ± 0.5 %, strain rate: systolic, -1.64 ± 0.03 1/s, diastolic, 1.68 ± 0.04 1/s) versus non-supported HF (strain: 9.9 ± 0.2 %, p&lt;0.001, strain rate: systolic, -0.83 ± 0.02 1/s, p&lt;0.001, diastolic, 0.86 ± 0.02 1/s, p&lt;0.001). All strain metrics were increased during DMVA compared to baseline (strain: 14.2 ± 0.4 %, p&lt;0.001, strain rate: systolic, -1.11 ± 0.03 1/s, p&lt;0.001, diastolic, 1.14 ± 0.04 1/s, p&lt;0.001). Composite strain waveforms aligned by systolic peak revealed an early diastolic boost during DMVA relative to baseline (see figure). Conclusions: Diastolic strain dynamics were significantly improved during DMVA in this model of progressive HF. Direct cardiac compression devices can impair diastolic function, which limits feasibility for circulatory support. This study further validates that DMVA restores near physiologic LV strain patterns during HF and uniquely augments diastolic function.

Abstract 11574: Clinical Changes and Predictors of Health Status in Patients With Atrial Fibrillation

Background: Recent clinical trials have shown the health status benefit of rhythm control, including catheter ablation (CA) over rate control for patients with atrial fibrillation (AF). However, the trials show population-averaged benefits, which complicates clinical interpretation; in reality, some patients may not benefit or even experience worsening health status after treatment. This study aimed to examine changes in patients' health status and identify predictors in a multicenter outpatient registry (KiCS-AF). Methods: KiCS-AF was a multicenter, prospective registry of patients with newly diagnosed AF collecting baseline and 1-year patient-reported health status. We examined changes in the Atrial Fibrillation Effect on QualiTy-of-life overall summary (AFEQT-OS) score over 1 year across different treatment strategies in patients with paroxysmal or persistent AF. We defined clinically important improvement and deterioration of health status as ≥5 points increase and decrease in AFEQT-OS score and no change as -5 to 5 points based on previous reports. Results: Overall, 1,960 patients were enrolled in this study, with mean AFEQT-OS scores of 76.7±17.7 and 85.4±14.8 at baseline and 1-year follow-up, respectively. The majority of patients (53.9%) experienced a clinically important improvement in health status, albeit a substantial number of patients experienced no change (28.7%) or worsening health status (17.4%). The proportion of patients with no change or worsening health status differed by treatment strategy (59.9%, 53.9%, and 32.0% in the rate control, antiarrhythmic drugs, and CA groups, respectively). After adjustment for baseline characteristics and AFEQT-OS scores, preserved baseline health status, older age (≥65 years), female sex, heart failure, and coronary artery disease were independent predictors of worsening health status in the overall cohort and the CA subgroup. Conclusion: In contemporary practice, a large proportion of patients showed improvement in health status, while a considerable number of patients experienced worsening or no change after intervention. Patient-centered care is essential to prevent the worsening of health status even after CA in high cardiovascular-risk, elderly, and female populations.

Association of Preoperative Renal-Resistive Index With Long-term Renal and Cardiovascular Outcomes After Cardiac Surgery

ObjectiveTo investigate the association of elevated preoperative renal resistive index (RRI) with persistent renal dysfunction, major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE) after cardiac surgery. DesignObservational cohort study. SettingUniversity hospital. ParticipantsNinety-six adult patients undergoing cardiac surgery. InterventionsRRI measurement the day before surgery. Measurements and Main ResultsFifty-eight patients (60%) had elevated RRI ≥0.70. Five years after surgery, persistent renal dysfunction (sustained decline in estimated glomerular filtration rate ≥25%) had occurred in 25 patients (26%), MAKE (persistent renal dysfunction, renal replacement therapy, or death) in 34 (35%), and MACE (myocardial infarction, unstable angina, decompensated heart failure, stroke, or cardiovascular death) in 28 (29%). RRI was higher in patients who developed persistent renal dysfunction (median, 0.78 [interquartile range, 0.74-0.82] vs. 0.70 [0.66-0.77], p = 0.001), MAKE (0.77 [0.72-0.81] vs. 0.68 [0.65-0.76], p = 0.002), and MACE (0.77 [0.72-0.81] vs. 0.70 [0.66-0.77], p = 0.006). Patients with elevated RRI had a significantly higher cumulative incidence of all long-term outcomes. After adjustment for baseline renal function and heart failure, elevated RRI was associated with persistent renal dysfunction (hazard ratio [HR], 5.82 [95% confidence interval, 1.71-19.9]), MAKE (HR, 4.21 [1.59-11.1]), and MACE (HR, 2.81 [1.03-7.65]). ConclusionsElevated preoperative RRI is associated with persistent renal dysfunction, MAKE and MACE after cardiac surgery. Preoperative RRI may be used for long-term risk assessment in patients undergoing cardiac surgery.

Electrocardiogram with Artificial Intelligence Assessment as a Predictor of Cardiac Events and Overall Survival in Patients Receiving Radiotherapy for Esophageal Cancer

Neoadjuvant (chemo)radiotherapy (RT) has demonstrated an overall survival (OS) benefit in esophageal cancer and constitutes part of the standard of care trimodality therapy. Unfortunately, subsequent cardiac toxicity can reduce the benefit of treatment. Our group aimed to study whether data from electrocardiograms (ECGs) could predict clinical outcomes and cardiac events after RT for esophageal cancer, allowing for identification of and early intervention for patients at high risk for cardiac toxicity. Included patients received at least 41.4 Gy of pre-operative or definitive photon or proton RT for esophageal cancer from 2015 through July 2022. All ECGs were assessed using a previously validated artificial intelligence assessment for atrial fibrillation (AF) and reduced ejection fraction (rEF) (Noseworthy et al. Lancet 2022). The model determined propensities for the development of multiple cardiac events, including AF and heart failure (HF). Medical records were reviewed for cardiac events and conditions prior to and after RT. A cohort of 491 patients was assembled, with 301, 121, and 364 patients having an ECG prior to, during, and after RT, respectively. Of these, 84% had malignancy in the lower third of the esophagus and 48% underwent esophagectomy. At last follow-up relative to baseline assessment, patients had increased propensity for rEF (median 0.013, interquartile range (IQR): 0.001-0.038 vs. median 0.022, IQR: 0.011-0.074, p < 0.0001) and AF (median 0.16, IQR: 0.04-0.40 vs. median 0.048, IQR: 0.01-0.19, p < 0.0001). Increases in AF propensity were associated with reduced OS (hazard ratio (HR) = 1.10 per 0.1 increase, 95% confidence interval (CI): 1.03-1.17, p = 0.0071). Baseline rEF propensity was predictive of future HF events (HR = 1.14, 95% CI: 1.07-1.22, p < 0.001) for all patients or after excluding the 172 (35%) patients with baseline HF (HR = 1.45, 95% CI: 1.19-1.76, p < 0.001). Among patients who did not have HF prior to radiotherapy, the development of HF was associated with reduced OS (HR = 1.60, 95% CI: 1.10-2.32, p = 0.014). Currently available cardiac dosimetric parameters, including heart mean/max doses, did not significantly correlate with cardiac outcomes. Patients who underwent esophagectomy had improved OS (HR = 0.62, 95% CI: 0.47-0.82, p = 0.0008) and were not more likely to develop cardiac toxicity. This analysis suggests that chemoradiotherapy for esophageal cancer can have significant impacts on a patient's propensity for cardiac events, which are associated with reduced OS. ECGs carry the potential to identify patients at greater risk for such events, and baseline ECGs with artificial intelligence assessment could select patients for increased surveillance or early intervention to further optimize the therapeutic ratio of RT.