Acute Heart Failure Events Research Articles

Chronic Kidney Disease Predisposes to Acute Congestive Heart Failure, Cardiogenic Shock, and Mortality in Patients Undergoing Percutaneous Coronary Intervention

The relations between degrees of chronic kidney disease (CKD) and congestive heart failure (CHF) events after percutaneous coronary intervention (PCI) are not well characterized. We sought to determine the relation between different stages of CKD and acute CHF events, including HF and cardiogenic shock (CS), and the impact of CKD stages on all-cause mortality after PCI. Patients who underwent PCI from 2009 to 2017 were identified from our institution's National Cardiovascular Disease Registry CathPCI Database. Patients were stratified by CKD stage 1 (estimated glomerular filtration rate [eGFR] ≥90 ml/min/1.73 m2), 2 (60 to 89), 3a (45 to 59), 3b (30 to 44), 4 (16 to 29), 5 (≤15), and current dialysis. The primary end point was composite HF events defined as acute HF or CS within 30 days after PCI, or in-hospital mortality, stratified by CKD and analyzed by multivariable regression after screening with univariate analysis (p <0.05 entry criteria). Patients with CKD stage 3a or worse had more composite HF events, with an increase in all components, compared with patients with CKD stages 1 to 2 (p <0.0001 for all comparisons). After multivariable adjustment, CKD stages 3a to 5 remained independent predictors of composite HF or in-hospital mortality events. eGFR remained a strong predictor of acute HF events after multivariable adjustment, with a model including eGFR and baseline and procedural characteristics achieving excellent discriminatory ability with area under the curve 0.92. In conclusion, baseline eGFR is a strong, independent predictor of acute HF events after PCI. CKD stages 3a to 5 independently predict HF events including HF decompensation and CS and are predictors of in-hospital mortality after PCI. Patients with baseline CKD may benefit from targeted interventions to limit acute HF events after PCI.

Serum Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and the Cardiovascular Disease Continuum: Insights from Hypertensive Urgencies and Acute Heart Failure Events

Background: Although TRAIL is a potent propapoptotic factor, its role in cardiovascular disease (CVD) remains unclear. This pilot exploratory study investigated serum TRAIL changes along the CVD continuum. We focused on two successive phases of this spectrum (systemic arterial hypertension and heart failure), with emphasis on acute cardiac events due to their immediate clinical significance. Methods: The study population included 90 age- and sex-matched patients hospitalized with hypertensive urgencies (HTUs) or acute decompensation episodes (ADHF). Key echocardiographic, endothelial, cardiometabolic, renal, and liver markers were assessed alongside TRAIL levels. Results: ADHF patients showed significantly elevated TRAIL concentrations, suggesting a progressive rise in TRAIL levels along the CVD continuum. They exhibited worse cardiac, hematologic, and renal profiles, with longer hospital stays and the cachexic phenotype. TRAIL correlated directly with asymmetric dimethylarginine, C-reactive protein, and admission potassium in ADHF patients. In hypertensive subjects, it correlated directly with asymmetric dimethylarginine and inversely with erythrocyte size variability. TRAIL may, thus, serve as a compensatory mechanism in HF, with potential as a biomarker for acute cardiovascular events. Conclusions: TRAIL dynamics provide valuable insights into CVD pathophysiology, particularly in acute settings, warranting further investigation to clarify its role in the broader context of apoptosis and cardiovascular health.

Prediction of acute heart failure events in patients with hypertrophic cardiomyopathy using RNA-Sequencing of plasma small non-coding RNAs

Abstract Background Hypertrophic cardiomyopathy (HCM) often causes acute heart failure (HF) events, which lead to worse quality of life and prognosis of patients with HCM. The recent emergence of cardiac myosin inhibitors to treat HCM highlights the clinical significance of identifying patients with HCM at high risk of developing acute HF events. However, no tools are available to predict acute HF events in HCM. Furthermore, the underlying molecular mechanisms responsible for the development of HF in HCM remain uncertain. Plasma RNA-sequencing (RNA-Seq) determines concentrations of thousands of small non-coding RNAs (sncRNAs) and has the potential to predict acute HF events in HCM. Purpose To predict acute HF events in patients with HCM using RNA-Seq of plasma sncRNAs and to determine signaling pathways dysregulated in those who subsequently experience acute HF events. Methods In this prospective, multi-center cohort study of patients with HCM, we conducted RNA-Seq of 3,740 plasma sncRNAs on 390 patients with HCM. The primary outcome was acute HF event defined as unplanned hospitalization due to HF. We developed a sncRNA-Seq-based model with linear discriminant analysis to predict acute HF events using data from one institution (training set, n=271). We also developed a reference model using clinical parameters with significant differences between patients with and without acute HF events in the training set. Then we tested the predictive ability in samples from the other institutions (test set, n=119), comparing the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the sncRNA-Seq-based model and the reference model using the Delong’s test. We also performed pathway analysis of microRNAs significantly (i.e., nominal P&amp;lt;0.05) associated with acute HF events. Results During a median follow-up time of 2.5 (interquartile 1.7–4.9) years, a total of 37 patients in the training set (14%) and 15 in the test set (13%) experienced an acute HF event. The model combining the reference model with the sncRNA-Seq-based machine learning model developed in the training set significantly outperformed the reference model (AUC 0.86 [95% confidence interval (CI) 0.74–0.97] vs. 0.68 [0.52–0.85], P=0.01, Figure) in the test set. The pathway analysis exhibited that both known pathways related to fibrosis, inflammation, and cell proliferation (e.g., the TGF-β signaling pathway) and novel pathways (e.g., the mTOR signaling pathway) were dysregulated with false discovery rate &amp;lt;0.01 in patients with HCM who subsequently experienced acute HF events (Table). Conclusions This study serves as the first to demonstrate the ability of plasma sncRNA-Seq to predict acute HF events in patients with HCM. Patients who subsequently experienced acute HF events exhibited dysregulation of both known and novel pathways.FigureTable

Evaluation of a New Telemedicine System for Early Detection of Cardiac Instability in Patients With Chronic Heart Failure: Real-Life Out-of-Hospital Study.

For a decade, despite results from many studies, telemedicine systems have suffered from a lack of recommendations for chronic heart failure (CHF) care because of variable study results. Another limitation is the hospital-based architecture of most telemedicine systems. Some systems use an algorithm based on daily weight, transcutaneous oxygen measurement, and heart rate to detect and treat acute heart failure (AHF) in patients with CHF as early on as possible. The aim of this study is to determine the efficacy of a telemonitoring system in detecting clinical destabilization in real-life settings (out-of-hospital management) without generating too many false positive alerts. All patients self-monitoring at home using the system after a congestive AHF event treated at a cardiology clinic in France between March 2020 and March 2021 with at least 75% compliance on daily measurements were included retrospectively. New-onset AHF was defined by the presence of at least 1 of the following criteria: transcutaneous oxygen saturation loss, defined as a transcutaneous oxygen measurement under 90%; rise of cardiac frequency above 110 beats per minute; weight gain of at least 2 kg; and symptoms of congestive AHF, described over the phone. An AHF alert was generated when the criteria reached our definition of new-onset acute congestive heart failure (HF). A total of 111 consecutive patients (n=70 men) with a median age of 76.60 (IQR 69.5-83.4) years receiving the telemonitoring system were included. Thirty-nine patients (35.1%) reached the HF warning level, and 28 patients (25%) had confirmed HF destabilization during follow-up. No patient had AHF without being detected by the telemonitoring system. Among incorrect AHF alerts (n=11), 5 patients (45%) had taken inaccurate measurements, 3 patients (27%) had supraventricular arrhythmia, 1 patient (9%) had a pulmonary bacterial infection, and 1 patient (9%) contracted COVID-19. A weight gain of at least 2 kg within 4 days was significantly associated with a correct AHF alert (P=.004), and a heart rate of more than 110 beats per minute was more significantly associated with an incorrect AHF alert (P=.007). This single-center study highlighted the efficacy of the telemedicine system in detecting and quickly treating cardiac instability complicating the course of CHF by detecting new-onset AHF as well as supraventricular arrhythmia, thus helping cardiologists provide better follow-up to ambulatory patients.

Telemedicine in Heart Failure in the COVID-19 and Post-Pandemic Era: What Have We Learned?

Numerous studies showed that patients with heart failure (HF) and COVID-19 are at high risk of in-hospital complications and long-term mortality. Changes in the organisation of the medical system during the pandemic also worsened access to standard procedures, increasing the general mortality in HF and forcing the systems to be reorganised with the implementation and development of telemedical technologies. The main challenges for HF patients during the pandemic could be solved with new technologies aimed to limit the risk of SARS-CoV-2 transmission, optimise and titrate the therapy, prevent the progression and worsening of HF, and monitor patients with acute HF events in the course of and after COVID-19. Dedicated platforms, phone calls or video conferencing and consultation, and remote non-invasive and invasive cardiac monitoring became potential tools used to meet the aforementioned challenges. These solutions showed to be effective in the model of care for patients with HF and undoubtedly will be developed after the experience of the pandemic. However, the multitude of possibilities requires central coordination and collaboration between institutes with data protection and cost reimbursement to create effective mechanisms in HF management. It is crucial that lessons be learned from the pandemic experience to improve the quality of care for HF patients.

CO184 US Population Burden of Acute Heart Failure Events and Hospitalization in Patients with Recent Worsening Heart Failure and Left Ventricular Ejection Fraction ≤30%

Increased risk of acute heart failure (HF) events has been reported for patients with HF with reduced ejection fraction (HFrEF) and worsening HF (WHF, ie, increasing signs and symptoms, including hospitalization/urgent treatment) or more severely reduced left ventricular ejection fraction (LVEF). We evaluated HF hospitalizations in patients with HFrEF, WHF, and LVEF ≤30% in real-world practice.

Hypotension at heart failure discharge: Should it be a limiting factor for drug titration?

BackgroundMedical treatment in Heart Failure (HF) with reduced ejection fraction (HFrEF; LVEF ≤40%) has shifted towards quadruple therapy. Maximum tolerated dose is the goal, yet no hypotension's cut-off point has been specified. In this work, we analyze the impact of intensive drug titration in clinical events, focusing on low blood pressure (BP) patients at hospital discharge. Methods and resultsRetrospective analysis of 713 patients with HFrEF discharged after an acute HF event (mean LVEF 30 ± 5%). Mean SBP was 112.4 ± 16.5 mmHg and 50.6% were discharged on triple therapy. We considered hypotension as a Systolic blood pressure (SBP) <100 mmHg (21.7% of patients, mean SBP was 112.4 ± 16.5 mmHg) and codified the intensity of drug therapy in 5 stages from untreated to very high therapy intensity. The impact of the intensity of treatment was analysed with a propensity score and increasing the intensity was associated in the whole cohort with a reduction of the composite outcome of all-cause mortality and HF readmission, (HR 0.69; CI95% 0.57–0.85, p < 0.001) and benefit in mortality was maintained for SBP < 100 mmHg (HR 0.42; CI95% 0.22–0.82; p = 0.011). Moreover, therapy intensity was clearly associated with lower risk of HF-hospitalization and death after the additional regression, considering SBP as a covariate, in the whole cohort (HR 0.70; CI95% 0.57–0.85; p < 0.001). ConclusionsIn this retrospective cohort analysis, patients with HFrEF and an acute-HF admission, intensive drug dose titration was related to better outcomes, even in patients with low blood pressure at hospital discharge. Therefore, hypotension is not a contraindication for NHB uptitration.

Pregabalin Does Not Increase Risk of Heart Failure Exacerbation in Patients With Pre-existing Heart Failure.

Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF). The objective of this study was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive. A retrospective cohort study of pregabalin users with HF were propensity score-matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups. The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58). This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.

Cardiac magnetic resonance predictors of readmission for heart failure in elderly vs not elderly patients after ST-segment elevation myocardial infarction

Abstract Background Patients with ST-segment elevation acute myocardial infarction (STEMI) have an increased risk of re-admission for acute heart failure (AHF). However, identification of patients at higher risk of AHF is challenging, especially in elderly individuals. The implications of cardiac magnetic resonance (CMR) imaging soon after the acute event for this specific purpose are unknown. Purpose We aim to study the clinical and CMR predictors of AHF in elderly and not elderly patients after STEMI. Methods STEMI patients treated with percutaneous coronary intervention and discharged from three university hospitals were included in a multicenter registry. We registered baseline clinical characteristics, echocardiographic parameters and early (1-week) CMR parameters - left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments). Univariate and multivariate comparisons were performed in elderly (&amp;gt;70 years) and not elderly (≤70 years) patients to predict AHF during follow-up. Results The cohort was comprised of 759 patients, of which 177 (23.3%) were elderly (&amp;gt;70 years). During a mean follow-up of 5.23±3.54 years, 79 (10.4%) patients presented AHF. In not elderly patients, Killip class at admission (HR 2.05 [1.32–3.17], p=0.001), anterior infarction (HR 3.43 [1.13–10.36], p=0.03) and CMR-LVEF (HR 0.94 [0.91–0.98] per increased %, p=0.001) independently predicted AHF. However, a combined risk score comprising these variables was not superior to CMR-LVEF alone to predict AHF during follow-up (AUC 0.81 [0.74–0.88] vs. 0.81 [0.73–0.88], p=NS). In elderly patients, CMR-LVEF was the only predictor of AHF in the final multivariable model (HR 0.94 [0.91–0.97], p&amp;lt;0.001), although its predictive power was moderate (AUC 0.68 [0.56–0.80], p=0.001). Most AHF events in the not elderly subgroup occurred in patients with reduced (≤40%) CMR-LVEF (71%), while in the elderly subgroup AHF occurred more frequently in patients with preserved (≥50%, 30%) or mildly reduced (40–49%, 32%) CMR-LVEF than reduced (≤40%) CMR-LVEF (38%). Conclusions LVEF quantified by CMR soon after STEMI can accurately predict the risk of AHF in not elderly (≤70 years) patients and identify those individuals at higher risk (i.e. CMR-LVEF ≤40%). However, in elderly (&amp;gt;70 years) patients most AHF occur in patients with CMR-LVEF &amp;gt;40%, emphasizing the need for better predictive strategies in this population. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III and “Fondos Europeos de Desarrollo Regional FEDER” and Conselleria de Educaciόn – Generalitat Valenciana.

Patients With Larger Left Atrial Appendage Orifice Presented Worse Prognosis Contributed by Acute Heart Failure After Left Atrial Appendage Closure.

Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P<0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P=0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P=0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.

Do adrenergic alpha-antagonists increase the risk of poor cardiovascular outcomes? A systematic review and meta-analysis.

Due to concerns regarding neurohormonal activation and fluid retention, adrenergic alpha-1 receptor antagonists (A1Bs) are generally avoided in the setting of heart disease, namely, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). However, this contraindication is mainly supported by ancient studies, having recently been challenged by newer ones. We aim to perform a comprehensive meta-analysis aimed at ascertaining the extent to which A1Bs might influence cardiovascular (CV) outcomes. We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science for both prospective and retrospective studies, published until 1 December 2020, addressing the impact of A1Bs on both clinical outcomes-namely, acute heart failure (AHF), acute coronary syndrome (ACS), CV and all-cause mortality-and on CV surrogate measures, specifically left ventricular ejection fraction (LVEF) and exercise tolerance, by means of exercise duration. Both randomized controlled trials (RCTs) and studies including only HF patients were further investigated separately. Study-specific odds ratios (ORs) and mean differences (MDs) were pooled using traditional meta-analytic techniques, under a random-effects model. A record was registered in PROSPERO database, with the code number CRD42020181804. Fifteen RCTs, three non-randomized prospective and two retrospective studies, encompassing 32851, 19287, and 71600 patients, respectively, were deemed eligible; 62256 patients were allocated to A1B, on the basis of multiple clinical indications: chronic HF itself [14 studies, with 72558 patients, including seven studies with 850 HFrEF or HF with mildly reduced ejection fraction (HFmrEF) patients], arterial hypertension (four studies, with 44184 patients) and low urinary tract symptoms (two studies, with 6996 patients). There were 25998 AHF events, 1325 ACS episodes, 955 CV deaths and 33567 all-cause deaths. When considering only RCTs, A1Bs were, indeed, found to increase AHF risk (OR 1.78, [1.46, 2.16] 95% CI, P<0.00001, i2 2%), although displaying no significant effect on neither ACS nor CV or all-cause mortality rates (OR 1.02, [0.91, 1.15] 95% CI, i2 0%; OR 0.95, [0.47, 1.91] 95% CI, i2 17%; OR 1.1, [0.84, 1.43] 95% CI, i2 17%, respectively). Besides, when only HF patients were evaluated, A1Bs revealed themselves neutral towards not only ACS, CV, and all-cause mortality events (OR 0.49, [0.1, 2.47] 95% CI, i2 0%; OR 0.7, [0.21, 2.31] 95% CI, i2 21%; OR 1.09, [0.53, 2.23] 95% CI, i2 17%, respectively), but also AHF (OR 1.13, [0.66, 1.92] 95% CI, i2 0%). As for HFrEF and HFmrEF, A1Bs were found to exert a similarly inconsequential effect on AHF rates (OR 1.01, [0.5-2.05] 95% CI, i2 6%). Likewise, LVEF was not significantly influenced by A1Bs (MD 1.66, [-2.18, 5.50] 95% CI, i2 58%). Most strikingly, exercise tolerance was higher in those under this drug class (MD 139.16, [65.52, 212.8] 95% CI, P<0.001, i2 26%). A1Bs do not seem to exert a negative influence on the prognosis of HF-and even of HFrEF-patients, thus contradicting currently held views. These drugs' impact on other major CV outcomes also appear trivial and they may even increment exercise tolerance.

Evolving therapeutic strategies for patients hospitalized with new or worsening heart failure across the spectrum of left ventricular ejection fraction.

Heart failure (HF) is a chronic, progressive, and increasingly prevalent syndrome characterized by stepwise declines in health status and residual lifespan. Despite significant advancements in both pharmacologic and nonpharmacologic management approaches for chronic HF, the burden of HF hospitalization—whether attributable to new‐onset (de novo) HF or worsening of established HF—remains high and contributes to excess HF‐related morbidity, mortality, and healthcare expenditures. Owing to a paucity of evidence to guide tailored interventions in this heterogeneous group, management of acute HF events remains largely subject to clinician discretion, relying principally on alleviation of clinical congestion, as‐needed correction of hemodynamic perturbations, and concomitant reversal of underlying trigger(s). Following acute stabilization, the subsequent phase of care primarily involves interventions known to improve long‐term outcomes and rehospitalization risk, including initiation and optimization of disease‐modifying pharmacotherapy, targeted use of adjunctive therapies, and attention to contributing comorbid conditions. However, even with current standards of care many patients experience recurrent HF hospitalization, or after admission incur worsening clinical trajectories. These patterns highlight a persistent unmet need for evidence‐based approaches to inform in‐hospital HF care and call for renewed focus on urgent implementation of interventions capable of ameliorating risk of worsening HF. In this review, we discuss key contemporary and emerging therapeutic strategies for patients hospitalized with de novo or worsening HF.

Reduced Heart Failure and Mortality in Patients Receiving Statin Therapy Before Initial Acute Coronary Syndrome

BackgroundThere is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF). ObjectivesThe aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD. MethodsData were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF. ResultsPrevious statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99). ConclusionsAmong adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173)

Elevated serum S100A12 levels are associated with increased risk of heart failure in patients with type 2 diabetes: the SURDIAGENE prospective study

The hyperglycemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE favors vascular disease and cardiac dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 for predicting major adverse cardiovascular events (MACE) and acute heart failure (AHF) in patients with type 2 diabetes (T2D) beyond established cardiovascular (CV) risk factors. Serum S100A12 levels were measured at baseline in T2D patients recruited in the SURDIAGENE prospective cohort. Outcomes were defined as occurrence of AHF requiring hospitalization, MACE and all-cause death. We used a proportional hazard model, and adjustments were performed for established CV risk factors. Among 1345 patients, 210 developed AHF, 505 MACE, and 446 died during a median follow-up of 84 months. Baseline serum S100A12 levels were associated with an increased risk of AHF (HR [95%CI] 1.28 [1.01-1.62], P = 0.0436), but neither death ( P = 0.1658) nor MACE ( P = 0.600). After adjustment for CV risk factors, S100A12 levels remained significantly associated with an increased risk of AHF (HR = 1.29 [1.01-1.65], P = 0.0422). After exclusion of 217 patients with basal NT-proBNP levels > 450 pg/ml suggesting pre-existing chronic HF, the predictive value of baseline serum S100A for future AHF events tended to be more significant (HR = 1.45 [1.06-1.97], P = 0.0202). In patients with T2D, increased serum S100A12 levels are independently associated with risk of future AHF events, but neither with risk of MACE nor death.

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AimsWe assessed the outcome of hospitalized coronavirus disease 2019 (COVID‐19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations.Methods and resultsInternational retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID‐19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF‐COVICAV). The primary endpoint was in‐hospital mortality. Of 1974 patients hospitalized with COVID‐19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in‐hospital mortality was 25% (n = 323/1282 deaths). In‐hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non‐HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P < 0.001). After adjusting, HF remained associated with in‐hospital mortality (OR 1.45 [95% confidence interval: 1.01–2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in‐hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24–4.29], P < 0.001).ConclusionsHospitalized COVID‐19 patients with HF are at increased risk for in‐hospital death. In‐hospital worsening of HF or acute HF de novo are common and associated with a further increase in in‐hospital mortality.

71. THE ASSOCIATION OF HIGHER SYSTOLIC BLOOD PRESSURE AT DISCHARGE AND DETERIORATION OF RENAL FUNCTION IN PATIENTS HOSPITALIZED FOR ACUTE DECOMPENSATED HEART FAILURE

Introduction: Deterioration of renal function over time is associated with worse outcomes in patients with Acute Decompensated Heart Failure. Deterioration of renal function was the long-term consequences of RAAS system activation in ADHF. Higher systolic blood pressure was the most common precipitating factor for the acute heart failure event. Moreover, it was known that higher SBP was the predictor of renal function deterioration. Therefore, we hypothesized that the levels of SBP at discharge would have associations with post-discharge outcomes in hospitalized ADHF. Method: The study included 51 patients admitted to our hospital between November 2020 and January 2021 with ADHF event, patients were classified into high creatinine value and normal creatinine value based on creatinine at discharged. SBP at discharge was the primary outcome between two groups. Result: We examined changes in creatinine and grouped it into high creatinine value (creatinine level ≥1.5 mg/dl) and normal creatinine value (creatinine level &lt;1.5 mg/dl). Overall, 60.8% (n = 31) of patients with AHDF were having higher creatinine value and 39.2% (n = 20) were having normal creatinine value. On Bivariate analysis, SBP at discharge was associated with higher creatinine value (p &lt; 0.07) and result showed positive correlation between SBP at discharge and high creatinine value (r = 0.306, p = 0.31). Conclusion: In patients admitted for ADHF, higher creatinine value was correlated with higher SBP at discharge.

Expansion of Monocytic Myeloid-Derived Suppressor Cells in Patients Under Hemodialysis Might Lead to Cardiovascular and Cerebrovascular Events

BackgroundThe specific mechanism of cardiovascular and cerebrovascular vasculopathy in the context of end-stage renal disease has not been elucidated. In the present study, we investigated the clinical impact of myeloid-derived suppressor cells (MDSCs) on hemodialysis patients and their mechanism of action.MethodsMDSCs were tested among 104 patients undergoing hemodialysis and their association with overall survival (OS) and cardiovascular and cerebrovascular events was determined.ResultsHemodialysis patients presented a significantly higher level of monocytic MDSCs (M-MDSCs) compared to healthy controls. M-MDSC were tested 3 months after first testing among 103 hemodialysis patients, with one patient not retested due to early death. The repeated results of M-MDSC levels were consistent with the initial results. Patients with persistent high level of M-MDSCs presented decreased OS, as well as increased stroke and acute heart failure events. As illustrated by multivariate Cox regression, M-MDSC was an independent predictor for OS and stroke events of hemodialysis patients. T cell proliferations were significantly abrogated by hemodialysis-related M-MDSCs in a dose-dependent manner. Besides, M-MDSCs presented higher levels of CXCR4 and VLA-4 compared to monocytes, which indicated their enhanced capability to be recruited to atherosclerotic lesions. The expression of arginase I and activity of arginase was also significantly raised in hemodialysis-related M-MDSCs. Human coronary arterial endothelial cells (HCAECs) presented increased capability to migration by coculture with M-MDSCs, compared with monocyte group. Arginase inhibitor and L-arginine abrogated the immune suppressive function and induction of HCAECs migration of hemodialysis related M-MDSC. Plasma IFN-γ, TNF-α and IL-6 were elevated in hemodialysis patients compared with healthy control. M-MDSC level was positively related to IL-6 level among hemodialysis patients. The plasma of hemodialysis patients induced M-MDSCs significantly compared with plasma from health donors. Besides, IL-6 neutralizing antibody significantly abrogated the induction. Neutralizing antibody of IFN-γ and TNF-α partially decreased the generation of arginase of the induced M-MDSC.ConclusionsM-MDSCs were elevated in ESRD patients under hemodialysis, and they exhibited a strong association with the risk of cardiovascular and cerebrovascular diseases. Hemodialysis related M-MDSC presented enhanced recruitment to atherosclerotic lesions, promoted the migration of endothelial cells through exhaustion of local L-arginine.

Abstract 16119: Dexrazoxane Role in the Prevention of Anthracycline Cardiotoxicity in Sarcoma Patients - A Meta-analysis

Introduction: Cardiotoxic side effects limit anthracycline use. Dexrazoxane has been proved cardioprotective in the setting of low-dose exposure, but its value in young sarcoma patients, who are treated with higher doses, remains elusive. Purpose: To perform a meta-analysis in order to appraise the efficacy and safety of dexrazoxane in sarcoma patients managed with anthracyclines. Methods: We systematically searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms “sarcoma”, “anthracycline” and “dexrazoxane”, from inception to June 1, 2020. Studies targeting cardiotoxicity, primary cancer outcome (suboptimal response to treatment, disease progression and oncologic death), secondary malignancy and mortality were selected. The primary endpoint was a composite of heart failure, ventricular arrhythmias and left ventricular systolic deterioration. Therapeutic arms were those of dexrazoxane and no drug or placebo. A random-effects model with Mantel-Haenszel method was used to calculate pooled odds ratios (OR) or mean differences (MD) and their 95% confidence interval (CI). Results: We encompassed 11 studies, of which 5 were prospective. 9 studies were conducted in children and doxorubicin was the most represented anthracycline. 1574 patients were included, of whom 679 were under dexrazoxane. There were 73 primary endpoint events, 21 secondary malignant neoplasms and 29 deaths. Cumulative doxorubicin dose was higher in the dexrazoxane arm (MD 70.66mg/m2, 95% CI 46.43-94.89, i 2 24%). Nevertheless, this agent reduced the odds of the primary endpoint (OR 0.37, 95% CI 0.20-0.71, i 2 11%), as well as numerically decreased acute heart failure events (OR 0.15, 95% CI 0.02-1.09, i 2 0%) and significantly halted left ventricular ejection fraction deterioration (MD 5.25%, 95% CI 1.98-8.53, i 2 26%). On the other hand, primary cancer outcome and risk of secondary malignancy did not differ between the two arms (OR 1, 95% CI 0.47-2.15, i 2 0% and OR 0.98, 95% CI 0.39-2.47, i 2 0%, respectively). Likewise, all-cause mortality was similar (OR 1.65, 95% CI 0.68-4.00, i 2 0%). Conclusion: Dexrazoxane seems to maintain its efficacy and safety in young sarcoma patients managed with high-dose anthracyclines.

Ischemic heart disease is more prevalent in low-income-countries and more often undertreated: data from report-hf

Abstract Background The pathogenic role of ischemic heart disease (IHD) in heart failure is well known. However, little is known about the global differences in the prognostic significance and treatment patterns of IHD in acute heart failure (AHF). Methods We prospectively enrolled 18,553 patients with AHF from 44 countries and 365 centers in the REPORT-HF registry. Patients with a history of coronary artery disease, an ischemic etiology of the AHF event or coronary revascularization were classified as IHD. Differences in clinical characteristics, treatment and outcome were analyzed. Results Compared to 9,344 (50%) patients without IHD, the 9,189 (50%) patients with IHD were older, more often had a left ventricular ejection fraction [LVEF] &amp;lt;40%, (HFrEF) and decompensated chronic HF (DCHF) and had a greater comorbidity burden. Despite patients from lower-income countries having a higher prevalence of IHD (55% vs. 45% in high-income countries), only 27% of patients with IHD from low-income countries were treated with medicines commonly prescribed for HF (Figure A) compared to 16% of patients with IHD from high income countries. After correction for clinical confounders and medication use, patients with IHD had a shorter “door-to-nitrates and -diuretics time” and worse 1-year mortality (hazard ratio: 1.18, 95% CI: 1.09, 1.27, Figure B) irrespective of geographic region (Pinteraction &amp;gt;0.1). We found a significant interaction for prognosis (Pinteraction &amp;lt;0.001) between IHD and HF diagnosis (DCHF vs. new-onset HF) as well as HF subtype (HFrEF vs. HF with preserved ejection fraction) respectively, such that IHD conveyed worse outcomes in patients with new-onset HF and HFrEF respectively in all world regions. Conclusion In this large global contemporary cohort of patients with AHF, IHD was more common in patients from low income countries, conveyed worse 1-year mortality, particularly in patients with new onset HF and patients with HFrEF. Despite worse outcomes, patients in regions with the greatest burden of IHD were more often undertreated. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

The Additional Prognostic Value of Ghrelin for Mortality and Readmission in Elderly Patients with Acute Heart Failure.

PurposeTo evaluate the prognostic value of ghrelin, a growth hormone-releasing peptide, for mortality and readmission in elderly patients with acute heart failure (AHF).Patients and MethodsWe measured plasma ghrelin and pro B-type natriuretic peptide (NT-proBNP) levels upon emergency admission in 241 prospectively recruited elderly AHF patients (61.0% men). The outcomes were all-cause mortality and/or readmission due to heart failure (HF). Multivariate Cox proportional hazards regression analyses were used to evaluate the prognostic value of ghrelin. Discrimination, calibration, and reclassification indices were compared between models, with or without ghrelin.ResultsDuring 1.2 years of follow-up, we observed 90 events (57 deaths and 33 readmissions due to HF). Plasma ghrelin levels were significantly elevated in elderly AHF patients, when compared to healthy control subjects (P < 0.001). Patients with events had significantly higher baseline ghrelin levels, when compared to those without (P < 0.001). Ghrelin levels were positively correlated with NT-proBNP levels and HF severity, whereas they were negatively correlated with nutritional status (all P < 0.05). Log transformed ghrelin levels were independently associated with AHF events (hazard ratio = 2.64, 95% confidence interval = 1.11–6.25, P = 0.028). The incorporation of ghrelin into the reference model, or reference with the NT-proBNP model, both improved C-statistics (from 0.742–0.780 and 0.836–0.857; P = 0.074 and 0.044, respectively), resulting in an improvement in net reclassification index (14.42% and 10.45%, P = 0.020 and 0.025, respectively), and integrated discrimination index (5.64% and 3.60%, both P < 0.001). Patients who displayed the above NT-proBNP and ghrelin median levels had a markedly higher risk of AHF adverse events (P < 0.001).ConclusionPlasma ghrelin is an independent predictor of adverse events in elderly AHF patients. Ghrelin may provide additional value to clinical parameters or NT-proBNP for prognostic risk stratification in AHF.