New-onset Heart Failure Research Articles

Value of left ventricular longitudinal strain in predicting overt heart failure in patients with Chagas disease and preserved left ventricular ejection fraction

Abstract Introduction Speckle-tracking echocardiography (STE) is an established tool to detect early myocardial contractile impairment. In Chagas disease patients, STE may be helpful to identify subtle myocardial damage with the potential of progression to heart failure. Purpose This study aimed to assess the value of STE in predicting heart failure in Chagas disease patients with preserved left ventricular ejection fraction (LVEF). Methods Patients with Chagas disease living in endemic area who had preserved LVEF (>50%) were selected for the study. Clinical evaluation, B-type natriuretic peptide (NT-ProBNP), electrocardiogram (ECG), and echocardiogram were performed at enrollment in 2015 to 2016 and in the follow-up visit between 2018 and 2019. Global longitudinal strain (GLS) derived from STE was analyzed offline. Peak GLS was calculated as the mean value from 18 segments of the left ventricle (Figure 1). The outcome was development of heart failure defined by elevation of NT-ProBNP levels, categorized according to age-specific cut-points for heart failure at the second evaluation. Patients with abnormal NT-ProBNP at baseline or those who died between the 2 visits were not included. Results A total of 692 were enrolled, mean age was 58 ± 12 years and 495 (72%) were women. Mean LVEF at baseline and follow-up visits were 63.4 ± 4.6% and 59.8 ± 11.2% (p<0.001). The median [IQR] time between visit 1 and visit 2 was 5.4 [4.5 - 5.8] years. Among patients alive and attending the second visit, 48 patients (7%) developed overt heart failure with overall incidence rate of 14.1 events per 1000 patient-years (95% CI 10.4-18.6). On multivariable analysis, independent predictors of new-onset heart failure were male sex (OR 2.30, 95% CI 1.02-5.18), age (OR 1.04, 95% CI 1.01-1.07), QRS duration (OR 1.03, 95% CI 1.01-1.04), left atrial (LA) volume indexed (OR 1.05, 95% CI 1.01-1.09), and GLS (OR 0.90, 95% CI 0.81-0.98). LVEF did not remain in the model. The C-statistic of the final model was 0.80 (95% CI 71-88) showing a good discrimination. Conclusions In a cohort of patients with Chagas disease from remote areas with preserved ejection fraction, GLS was an important predictor of progression to overt heart failure, after adjustment for sex, age, QRS duration and LA volume. GLS was associated with further increased NT-ProBNP levels, which is useful to guide heart failure management, irrespective of systolic dysfunction.

Abstract 12424: Left Atrial Strain and Incident Heart Failure in Older Adults

Introduction: The prevalence of heart failure (HF) is rising, particularly in older adults. Left atrial (LA) dysfunction is commonly seen in HF, but it is unclear if it predicts onset or contributes to its development. Hypothesis: LA strain reduction is associated with incident HF in the general elderly population, independent of other risk factors and even in the presence of normal LA volume. Aims: We aimed to investigate the association between reduced LA strain (LAε) and strain rate (LASR) and incident HF in older adults without history of HF or atrial fibrillation (AF), adjusting for HF risk factors and echocardiographic parameters. Methods: We examined 795 participants aged ≥55 from the Cardiovascular Abnormalities and Brain Lesions (CABL) study with no history of HF or AF. LAε pos , LASR pos , LASR early-neg , and LASR late-neg were assessed using speckle-tracking echocardiography for global, reservoir, conduit and pump function, respectively. Incident HF was detected through standardized interviews, in-person visits, active hospital surveillance of admission and discharge ICD-9 codes. LA strain's association with incident HF was assessed using a cause-specific hazards regression model, adjusting for HF risk factors, including incident AF. Results: Mean age was 70.9±9.2 years (297 men, 498 women). During a mean follow-up of 11.4 years, 215 participants (27.0%) developed new-onset HF; incident AF occurred in 98 (12.3%). Left ventricular ejection fraction and global longitudinal strain were not associated with new-onset HF (p=0.06 and p=0.23, respectively). All LA strain measures at baseline were significantly associated with new-onset HF (all p<0.01). In multivariable analysis, only LASR late-neg (adjusted HR per SD decrease 2.31, 95% CI 1.12-4.43) remained independently associated with new-onset HF, after adjusting for LA volumes, left ventricular systolic function, and incident AF. LASR late-neg was especially associated with incident HF in participants with normal LA size (HR 8.64, CI 3.10-24.08). Conclusion: Reduced LA strain during atrial contraction is independently associated with new-onset HF in older adults. LA strain measurement may improve HF risk stratification in older adults, even in the presence of normal LA volume.

Abstract 15808: Sodium Glucose Co-Transporter-2 Inhibitors and Clinical Outcomes in Cancer Patients Treated With Anthracyclines

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been proven to improve clinical outcomes in heart failure (HF). However, there remains a paucity of data on the potential cardioprotective impact of SGLT2i in cancer patients receiving anthracyclines. Aim: To evaluate if SGLT2i use is associated with improved outcomes in anthracycline-treated cancer patients. Methods: Using TriNetX Global Research Network from 2013 to 2021, patients diagnosed with cancer and receiving anthracycline therapy were identified and categorized into those who were taking SGLT2i versus those who were not. A 1:1 propensity score matching was used to control for baseline characteristics between the two groups. Patients were followed for 2 years. The primary endpoint was all-cause mortality and secondary endpoints were new-onset HF, acute HF exacerbation, myocardial infarction, new-onset atrial fibrillation/flutter, and all-cause hospitalization. Results: A total of 82,369 anthracycline-treated cancer patients were identified. After propensity score matching application, 1,412 patients were included in our analysis (706 patients in each group). Patients on SGLT2i had lower rates of all-cause mortality (OR: 0.7 [95% CI: 0.56, 0.88]; P=0.002), acute HF exacerbation (OR: 0.64 [95% CI: 0.41-1]; P=0.048), and new-onset atrial fibrillation/flutter (OR: 0.52 [95% CI: 0.33, 0.8]; P=0.003) compared to those not on SGLT2i. The incidence of myocardial infarction, new-onset HF, and all-cause hospitalization were similar between the two groups (Figure). Conclusion: Among cancer patients receiving anthracyclines, SGLT2i were associated with lower rates of mortality, acute HF exacerbations, and new-onset atrial fibrillation/flutter and similar rates of myocardial infarction, new-onset HF, and hospitalization.

Abstract 13405: Cardiac Computed Tomography Variables for Prediction of New-Onset Heart Failure: Multi-Ethnic Study of Atherosclerosis

Introduction: Heart failure (HF) prediction models utilize clinical variables. The purpose of this study was to determine if addition of cardiac computed tomography (CT) variables could improve discrimination of HF prediction scores. Methods: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort between 45 to 84 years old and free of clinical cardiovascular disease at baseline, with complete clinical data and cardiac CT were included to evaluate new-onset HF during the follow-up period. Cardiac CT variables analyzed included left ventricular size index (LVSi) and calcification of the coronary arteries (CAC), aortic valve (AVC), mitral valve (MVC), and thoracic aorta (TAC). We evaluated if CT variables improved the Pooled Cohort equations to Prevent HF (PCP-HF) score (an internally and externally validated model of 33,010 patients predicting 10-year risk of new-onset HF). Results: Among 6,667 MESA participants (52.7% female), 426 events of new-onset HF occurred during the follow-up period. After the Cox model was adjusted for cardiac CT and PCP-HF score variables, CAC (HR 1.10; 95% CI 1.05-1.15; p<0.001), AVC (HR 1.08; 95% CI 1.03-1.13; p=0.002), MVC (HR 1.06; 95% CI 1.01-1.12; p=0.015), and LVSi (HR 1.14; 95% CI 1.10-1.18; p<0.001) were all significantly associated with new-onset HF. After using time-dependent ROC and stratifying by sex, AUC discrimination of new-onset HF with the PCP-HF score was improved by the inclusion of cardiac CT variables. In females, the AUC for 10-year risk of new-onset HF improved from 0.80 to 0.86 with the addition of cardiac CT variables. In males, the AUC for 10-year risk of new-onset HF improved from 0.77 to 0.84 with the addition of cardiac CT variables. Conclusions: In addition to traditional clinical risk factors, cardiac CT variables provide anatomic risk factors that improve the prediction of new-onset HF. Coronary and valvular calcification may signal poorly controlled clinical risk factors that are often associated with HF. LVSi may reflect left ventricular remodeling associated with HF. More studies are needed to further elucidate the relationship between cardiac CT anatomic risk factors and HF.

Abstract 16201: Use of Cardiac Computed Tomography (CT) Imaging Biomarker Variables for the Prediction of Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis

Introduction: Several predictive heart failure (HF) models exist to determine incident HF. We aimed to create a model that uses cardiac CT imaging biomarkers to improve discrimination scores of incident HF. Hypothesis: Cardiac CT variables increase predictive abilities of the Pooled Cohort Equations to Prevent HF (PCP-HF) score (a validated 10-year risk of new-onset HF prediction model) in all HF, HFrEF, and HFpEF. Methods: MESA participants aged 45-84 years old and free of clinical CVD who completed a cardiac CT were included for study analysis. The outcome of interest was new-onset HF. Clinical risk factors were obtained. Cardiac CT variables analyzed included left ventricular size index (LVSi) and calcifications of coronary arteries (CAC), aortic valve (AVC), mitral valve (MVC), and thoracic aorta (TAC). Results: Among 6,667 MESA study participants who underwent cardiac CT, 426 events of new-onset HF occurred during the follow-up period. Among the 426 events, 173 (40.6%) were categorized as HFrEF, 193 (45.3%) were categorized as HFpEF, and 60 (14.1%) had missing ejection fraction data. The reported data is based on the Cox model adjusted for all CT variables in one model with log(PCP-HF). For all incident HF (preserved and reduced), CAC (HR 1.10 95% CI 1.05-1.15, p<0.001) and LVSI (HR 1.14 95% CI 1.10-1.18, p<0.001) were statistically significant with an improvement in c-stat from .773 to .805. For HFpEF, CAC (HR 1.07 95% CI 1.01-1.14, p<0.025), AVC (HR 1.08 95% CI 1.00-1.16, p<0.037) and MVC (HR 1.12 95% CI 1.05-1.19, p<0.001) were statistically significant with an improvement in c-stat from .782 to .800. For HFrEF, CAC (HR 1.15 95% CI 1.08-1.23, p<0.001) and LVSI (HR 1.28 95% CI 1.23-1.34, p<0.001) were statistically significant with an improvement in c-stat from .751 to .815. Conclusions: Current HF prediction models, including PCP-HF model, are based on clinical risk factors. As evidenced by this model CAC, AVC, MVC and LVSi have statistical significance with improvement in c-statistics of the PCP-HF model when adjusted for CT variables. HFpEF and HFrEF have different CT variables with enhanced predictive ability.This study emphasizes the need to study the utility of cardiac CT imaging biomarkers in the development of an incident HF predictive model.

Abstract 13812: Daily Marijuana Use is Associated With Incident Heart Failure: “All of Us” Research Program

Background: With the increasing state-level legalization of marijuana across the United States, its use has increased exponentially, especially among the youth. However, a lot remains unknown concerning its cardiovascular health implications. We sought to assess the association between the frequency of marijuana use and new-onset heart failure (HF). Methods: Using the NIH-sponsored “All of Us” Research Program, we performed a prospective analysis of participants’ survey data and Electronic Health records (EHR). We excluded patients with a baseline EHR diagnosis of HF. Marijuana use was defined as any unprescribed use or if prescribed, use beyond prescribed doses, and was collected using the NM ASSIST instrument. We determined the association between the frequency of marijuana use and incident HF using Cox proportional hazards models adjusted for demographic and socioeconomic factors, diabetes mellitus, hypertension, hyperlipidemia, BMI, alcohol use and smoking status. Results: From a final population of 156,999, there were 2958 events within a median follow-up time of 45 months. Compared to never users, daily marijuana users had an increased risk of incident HF (aHR - 1.34, 95% CI 1.04-1.72). In subgroup analyses, frequency of marijuana use was not associated with incident HFrEF nor HFpEF. There was no evidence of effect modification by age, sex at birth nor smoking status. The relationship was attenuated after addition of coronary artery disease diagnosis as a time varying covariate in our main model (aHR - 1.27, 95% CI 0.99-1.62). Implication: Data on the cardiovascular effects of marijuana use is limited. To our knowledge this is the first prospective analysis on the association of marijuana use and HF. Our study suggests daily marijuana use is associated with HF. More research into the cardiovascular effects of marijuana is needed to enable clinicians provide the public with high quality information on the health implications of marijuana and to guide policies.

Abstract 14071: Plasma Protein Concentrations and Risk of Incident Cardiovascular Diseases in the UK Biobank

Introduction: Profiling of plasma proteins has the potential to improve diagnosis, predict disease and reveal new biologic pathways for cardiovascular disease (CVD). Objectives: We tested the associations of circulating proteins with new-onset coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), and aortic stenosis (AS) in the UK Biobank. Methods: The initial dataset consisted of 52,705 individuals and 1,463 proteins measured using the Olink platform. A total of 47,665 unrelated individuals without prevalent CVD and 1,459 proteins were retained after quality control. Cox proportional hazards models were used to evaluate associations of protein levels at baseline with incident CAD, AF, HF, and AS. Models were adjusted for age, age 2 , race, first ten principal components of genetic ancestry, sex, smoking, BMI, SBP, antihypertensive and lipid-lowering medication use, DMII, serum creatinine, LDL and HDL cholesterol, and Townsend deprivation index. The four outcomes were incorporated as time-varying covariates. Results: Among the 47,665 individuals, mean (SD) age was 56.8 (8.2) years, 25,674 (53.9%) were female, and 44,691 (93.8%) white. Over a median follow-up of 11.1 years, there were 2,941 (6.2%), 2,502 (5.2%), 1,470 (3.1%) and 420 (0.9%) incident cases of CAD, AF, HF, and AS, respectively. Multivariable-adjusted Cox regression revealed 270, 156, 385, and 21 significant associations (P < 8.6 x 10-6) for CAD, AF, HF, and AS, respectively. Fifteen biomarkers overlapped across all outcomes. The strongest associations for CAD, AF, HF, and AS were with GDF-15 (HR = 1.33, 95% CI = 1.28 - 1.39), NT-proBNP (HR = 1.83, 95% CI = 1.75 - 1.91), HE4 (encoded by WFDC2; HR = 1.67, 95% CI = 1.57 - 1.77), and GDF-15 (HR = 1.51, 95% CI = 1.43 - 1.59), respectively. NT-proBNP, IGFBP-4 and HE4 were the strongest overlapping associations. Conclusions: High-throughput proteomics may offer new mechanistic insights and improve risk prediction for common CVDs.

Abstract 11805: Hidden Hazards: Unraveling Risk Factors for New-Onset Acute Heart Failure in Liver Transplant Recipients

Introduction: Heart failure with reduced ejection fraction (HFrEF) following liver transplantation (LT) is associated with increased morbidity and mortality. Early identification and optimization of risk factors associated with development of heart failure in LT recipients could improve cardiac and liver transplant outcomes. Hypothesis: The study's primary objectives were to ascertain the incidence of new-onset HFrEF post-liver transplant, identify the associated risk factors and understand their clinical outcomes. We hypothesized that certain demographic and clinical factors may predispose liver transplant recipients to develop new-onset HFrEF. Methods: Our retrospective cohort study included 568 liver transplant recipients at our center. Patients were categorized based on whether or not they developed new-onset HFrEF post LT We utilized descriptive statistics, chi-square tests, and logistic regression analyses to investigate potential associations between patient demographics, clinical risk factors and the development of new HFrEF . Results: The incidence of acute heart failure post-transplant was 8% (n=43). Within this group, 51% had HFrEF (LVEF<40%), 37% HFmrEF (LVEF 40-49%),12% HF with preserved EF. LVEF was significantly lower in the new-onset HF group [40(30-45) vs 60(55-65), p<0.001]. Median time to HF onset was 25 days. Coronary artery disease (OR 2.53, 95% CI 1.01-6.35, p=0.04) and malignancy history (OR 2.35, 95% CI 1.15-4.81, p=0.02) were significant predictors of new onset HFrEF. New onset HFrEF was associated with higher 180-day mortality (14% vs 6%, OR 2.57, 95% CI 1.00-6.56, p=0.048). Conclusions: Coronary artery disease and history of malignancy were identified as risk factors for new-onset HFrEF post-LT. Additional research is needed to better understand the impact of CAD and malignancy on cardiac and liver transplant outcomes that may result in improved patient care.

Abstract 16312: Sex-Based Differences in Response to Interleukin-1 Blockade With Anakinra in Patients With ST-Segment Elevation Myocardial Infarction

Introduction: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra in this setting. Methods: We analyzed sex-based differences in the systemic inflammation (CRP levels) and composite end-point of new-onset HF or death in patients with STEMI from three different Virginia Commonwealth University Anakinra Response Trial (VCU-ART) randomized clinical trials. Data are reported as median and interquartile range [IQR] or number and percentage (%). Kaplan-Meier curves for event-free survival were constructed for the time-dependent composite endpoint and compared using the log-rank analysis. Results: We analyzed 139 patients from three VCU-ART trials, 29 (21%) were women while 110 (79%) were men. Baseline CRP was higher in women compared to men (8.9 [5.2-13.5] vs 4.2 [2.1-7.7] mg/L, P<0.001). Twenty-two (75%) women and 62 (56%) men were treated with anakinra. Area under the curve (AUC)-CRP at 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs 223 [119-374] mg day/L) and in women (73 [46-313] vs 242 [102-988] mg day/L) (P<0.001 at ANOVA for multiple groups, P for interaction 0.22) Figure A . The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs 14 [29.1%]) and in women (3 [13.6%] vs 2 [28.5%]) (P=0.019 at ANOVA, P for interaction 0.44) Figure B . There were no statistically significant differences between women and men in AUC-CRP and HF events when comparing separately the anakinra and placebo groups (all P>0.05). Conclusions: Women were underrepresented in the VCU-ART trials, they appeared to have higher CRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Abstract 12391: Correlation of Admission Heart Rate With MACE Among ST-segment Elevation Myocardial Infarction Patients (killip1) Undergoing Primary Percutaneous Coronary Intervention

Introduction: Different admission heart rate (AHR) levels are frequently observed in ST-segment elevation myocardial infarction (STEMI) patients. However, it is not clear whether AHR is related to the occurrence of major adverse cardiovascular effects (MACE) after pPCI. Hypothesis: We aim to explore the possible correlation between AHR and MACE after STEMI patients receive the primary percutaneous coronary intervention (pPCI). Methods: The Chinese STEMI pPCI Registry was registered with ClinicalTrials.gov (NCT04996901). We analyzed 5586 patients with STEMI who underwent pPCI in a multi-center study in China, and patients were grouped according to the AHR greater or less than 70 bpm. Patients’ in-hospital MACE referred to new-onset heart failure and death. The association between AHR and in-hospital MACE was assessed in Logistic regression analysis. Results: 4004 patients were enrolled ultimately, including 1105 patients with AHR< 70 bpm and 2899 patients with AHR≥ 70 bpm. After multivariate adjustment for age, gender, DBP, HR, smoking, hypertension, et al., the OR of MACE in patients with AHR ≥ 70 bpm was 1.573-1.581 times that of the other group in calibration Model I to IV. Subgroup analysis showed that it was also observed in the young (<60 years old) or the old (≥60 years old), male or female, Left anterior descending (LAD), and Right circumflex artery (RCA) patients (all P <0.05). We still found that AHR was a risk factor for in-hospital MACE after excluding those patients with a history of MACE, RCA occlusion and AHR less than 50 bpm or greater than 90 bpm in sensitivity analysis. ROC curve of AHR in predicting the occurrence of MACE after pPCI was 0.699. The cubic spline also confirmed that the risk of MACE decreased significantly with the reduction of AHR. Conclusions: In STEMI patients undergoing pPCI, elevated AHR (≥70 bpm) identifies those at increased risk of in-hospital MACE. AHR less than 70 bpm may be a protective factor to avoid the occurrence of MACE.

Abstract 16249: A Case of Myocarditis and Pneumonitis Associated With Pembrolizumab Therapy

Introduction: Immune checkpoint inhibitors (ICI) are a novel therapy that activates antitumor immunity but can have varied immune-related adverse effects. As ICI therapy is used to treat malignancy, cases of autoimmune myocarditis and heart failure increase, thought to be due to PD-1 inhibition, which may be potentially fatal. Case presentation: A 37 yo female with history of autoimmune hepatitis and stage III melanoma on Pembrolizumab (ninth cycle 1.5 months prior) presented with chest pain, tachycardia, fatigue, dyspnea, and fever. Lab studies were notable for elevated troponin, lactic acidosis, and disseminated intravascular coagulation (DIC). CT thorax showed asymmetric ground glass opacities, concerning for ICI pneumonitis. Echocardiogram showed an LVEF of 15% with global hypokinesis. She was treated for severe sepsis, DIC, and respiratory failure, temporarily requiring intra-aortic balloon pump. Heart failure guideline-directed medical therapy (GDMT) was started. Clinical presentation was concerning for acute myocarditis related to ICI therapy as a cause for new cardiomyopathy. A cardiac MRI (CMR) revealed subepicardial late gadolinium enhancement (LGE) along the basal inferior/inferolateral wall segments concerning for myocarditis. Corticosteroids with a prolonged taper were started. Endomyocardial biopsy of the septum (EMB) was negative. Her clinical status improved and repeat echo showed LVEF recovery up to 45%. Discussion: Endomyocardial biopsy (EMB) provides definitive diagnosis of myocarditis and is recommended (Class I) for new-onset heart failure with hemodynamic compromise and/or arrhythmias. Although our patient’s EMB was negative (likely due to limitation of sample location), she met the 2013 ESC guideline diagnostic criteria for myocarditis with elevated troponin, functional and structural abnormalities on cardiac imaging. With increased utilization of ICI therapy in the management of aggressive malignancies, it is important to monitor for potentially adverse effects such as autoimmune myocarditis. Standard treatment is prompt initiation of corticosteroids, though newer studies report successful treatment with immunomodulators, such as abatacept and ruxolitinib, if steroids are unsuccessful.

New onset heart failure with reduced ejection fraction management: single center, real-life Tunisian experience

BackgroundHeart failure (HF) is a serious and frequent pathology. It represents a major public health problem. We have few data about this pathology in our country. The aim of our study is to determine the epidemiological, clinical, therapeutic, and prognostic characteristics of new-onset HF with reduced left ventricular ejection fraction (HFrEF) and to study the degree of conformity of the management of HF with international recommendations.ResultsOur study population includes 210 patients hospitalized for HFrEF newly diagnosed. The average age of our patients was 64 ± 12 years. A male predominance was noted with a sex ratio of 2.8. The main etiology of HF was ischemic heart disease noted in 97 patients (46.2%). The average LVEF is 33 ± 6%. The triple combination (angiotensin-converting enzyme inhibitors + beta blockers + Mineralocorticoid Receptor Antagonists) was prescribed in 75 patients (35.7%). The quadruple combination (angiotensin-converting enzyme inhibitors + beta blockers + Mineralocorticoid Receptor Antagonists + Sodium-Glucose Co-Transporter 2 inhibitors) was prescribed in 17 patients (8.1%). Myocardial revascularization was indicated in 97 patients (46.6%) and valve surgery was indicated in 49 patients (23.3%). Hospital mortality was 3.8% and at 1 year 18.1%. Among the 192 patients followed during the first year after discharge from hospital, 81 patients had to be re-hospitalized, i.e., a 1-year rehospitalization rate of 42.2%.ConclusionsOur study highlighted the epidemiological and clinical features of HF in a Tunisian care center, revealing our patient management deficiency. This pushes us to have a new Tunisian register to enable a better statistical analysis and lead to more relevant conclusions.

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Different outcomes between iso-osmolar and low-osmolar contrast media in acute myocardial infarction with renal impairment.

The selection of appropriate contrast media (CM) remains an important issue in terms of renal preservation in patients with acute myocardial infarction (AMI) and renal impairment scheduled for percutaneous coronary intervention (PCI). We compared the clinical outcomes of patients with AMI and renal impairment, depending on the CM type (iso-osmolar CM [IOCM] vs. low-osmolar CM [LOCM]) that was used during PCI. From the Convergent Registry of Catholic and Chonnam University for Acute Myocardial Infarction, 3174 post-PCI patients with AMI and renal impairment were subdivided into two groups (IOCM [n = 2101] and LOCM [n = 1073]). Regarding in-hospital clinical outcomes, the IOCM group had a higher peak creatinine (Cr) level and lower "Cr differential" than the LOCM group. A higher proportion of dialysis was noted in the IOCM group. In 30-day clinical outcomes, the IOCM group showed higher incidence of new-onset heart failure (HF) but lower incidence of revascularization than the LOCM group. The differences in in-hospital and 30-day clinical outcomes were attenuated after inverse probability of treatment weighting, except for new-onset HF. All other variables in 30-day clinical outcomes, including all-cause death, non-fatal myocardial infarction, cerebrovascular accidents, stent thrombosis, and any dialysis events, were similar between the two groups. IOCM use did not prevent future incidence of dialysis compared to LOCM use in AMI patients with renal impairment.

Sex Disparities in Management and Outcomes Among Patients With Acute Coronary Syndrome

Sex disparities in the management and outcomes of acute coronary syndrome (ACS) have received increasing attention. To evaluate the association of a quality improvement program with sex disparities among patients with ACS. The National Chest Pain Centers Program (NCPCP) is an ongoing nationwide program for the improvement of quality of care in patients with ACS in China, with CPC accreditation as a core intervention. In this longitudinal analysis of annual (January 1, 2016, to December 31, 2020) cross-sectional data of 1 095 899 patients with ACS, the association of the NCPCP with sex-related disparities in the care of these patients was evaluated using generalized linear mixed models and interaction analysis. The robustness of the results was assessed by sensitivity analyses with inverse probability of treatment weighting. Data were analyzed from September 1, 2021, to June 30, 2022. Hospital participation in the NCPCP. Differences in treatment and outcomes between men and women with ACS. Prehospital indicators included time from onset to first medical contact (onset-FMC), time from onset to calling an emergency medical service (onset-EMS), and length of hospital stay without receiving a percutaneous coronary intervention (non-PCI). In-hospital quality indicators included non-PCI, use of statin at arrival, discharge with statin, discharge with dual antiplatelet therapy, direct PCI for ST-segment elevation myocardial infarction (STEMI), PCI for higher-risk non-ST-segment elevation ACS, time from door to catheterization activation, and time from door to balloon. Patient outcome indicators included in-hospital mortality and in-hospital new-onset heart failure. Data for 1 095 899 patients with ACS (346 638 women [31.6%] and 749 261 men [68.4%]; mean [SD] age, 63.9 [12.4] years) from 989 hospitals were collected. Women had longer times for onset-FMC and onset-EMS; lower rates of PCI, statin use at arrival, and discharge with medication; longer in-hospital delays; and higher rates of in-hospital heart failure and mortality. The NCPCP was associated with less onset-FMC time, more direct PCI rate for STEMI, lower rate of in-hospital heart failure, more drug use, and fewer in-hospital delays for both men and women with ACS. Sex-related differences in the onset-FMC time (β = -0.03 [95% CI, -0.04 to -0.01), rate of direct PCI for STEMI (odds ratio, 1.11 [95% CI, 1.06-1.17]), time from hospital door to balloon (β = -1.38 [95% CI, -2.74 to -0.001]), and rate of in-hospital heart failure (odds ratio, 0.90 [95% CI, 0.86-0.94]) were significantly less after accreditation. In this longitudinal cross-sectional study of patients with ACS from hospitals participating in the NCPCP in China, sex-related disparities in management and outcomes were smaller in some aspects by regionalization between prehospital emergency and in-hospital treatment systems and standardized treatment procedures. The NCPCP should emphasize sex disparities to cardiologists; highlight compliance with clinical guidelines, particularly for female patients; and include the reduction of sex disparities as a performance appraisal indicator.

New-onset heart failure in infants: when the aetiological diagnosis becomes a challenge.

The onset of heart dysfunction in infants can result from either inherited factors or viral infections, both of which may involve inflammation. However, the precise role of EMB and CMR in determining the etiology of such cases remains poorlydefined. While CMR demonstrates high sensitivity in detecting inflammation, our experience suggests that it may not effectively differentiate between these two groups. A comprehensive diagnostic approach is essential when addressing this challenge, which includes considering EMB (with attention to the number of T-lymphocytes and the presence of oedema), specific CMR criteria, notably LGE and tissue mappings, as well as the identification of viral agents in cardiac tissue andtroponin levels. Additionally, genetic tests should be conducted when evaluating these patients. • EMB is the gold standard diagnostic test for myocarditis but it is notuniversally accepted. • The diagnostic value of the 2018-LLC in pediatric patients is still undefined. • Both EMB and CMR may show inflammation in infants with new-onset heart failure of any aetiology. • A global approach should be used when facing this diagnostic challenge, including the EMB (number of T-lymphocytes and oedema), some CMR criteria, specially LGE and mappings, the detection of viral agents in cardiac tissue and troponins. Genetic tests should also be performed when studying these patients.

Long-term prognostic significance of history of cancer and atrial fibrillation in coronary artery disease

BackgroundLimited data exist on the prognostic significance of a history of cancer and atrial fibrillation (AF) in patients with coronary artery disease (CAD). This study aimed to evaluate the associations among a history of cancer, AF, and long-term prognosis in patients with CAD. MethodsWe studied 3,233 patients with CAD (69 ± 11 years; women, 23%) in a multicenter hospital-based cohort study, the CHART-2 and related a history of cancer and AF to cardiovascular outcomes with a median follow-up of 10.8 years. ResultsOf the 3,233 patients enrolled, 10.7% and 11.2% had a history of cancer and AF, respectively, while 2.8% had both. Patients with AF and a history of cancer were characterized by older age, male sex, and higher BNP levels. Anticoagulant use with warfarin or direct oral anticoagulants increased from 43% at baseline to 56% at 10 years in patients with CAD with AF and no history of cancer and increased from 49% to 83% in those with both. Patients with CAD with both comorbidities had a higher risk of a composite outcome including stroke, thrombosis, and major bleeding (Hazard Ratio [HRadjusted], 2.26; 1.50–3.40, P < 0.001). Furthermore, patients with both comorbidities had a higher risk of all-cause death (1.55; 95% confidence interval [CI] 1.12–2.12, P = 0.007) including cancer death (2.62; 1.51–4.54, P = 0.001), and new-onset heart failure (HF) requiring hospitalization (2.47; 1.54–3.96, P < 0.001). ConclusionsThese results demonstrate that CAD patients with a history of cancer and AF have an increased risk of composite outcomes, including stroke, systemic thrombosis, major bleeding, all-cause death, cancer-related death, and new-onset HF.

Proenkephalin Levels and Its Determinants in Patients with End-Stage Kidney Disease Treated with Hemodialysis and Peritoneal Dialysis.

Recently, proenkephalin A (PENK A) has been shown to reflect glomerular dysfunction and to predict new-onset acute kidney injury and heart failure. While previous studies have investigated PENK A as a biomarker in individuals with preserved renal function, PENK A concentration in patients with end-stage kidney disease (ESKD) was not investigated. Plasma PENK A concentration was assessed in 88 patients with ESKD treated with hemodialysis (HD) or peritoneal dialysis (PD), and its associations with kidney function and heart failure indicators were investigated. In HD patients, the difference in PENK A levels before and after hemodialysis, was measured and further assessed for an association with the type of HD membrane used. PENK A levels did not differ significantly between HD and PD patients. In HD patients, the median PENK A concentration was significantly higher before than after hemodialysis (1.368 vs. 2.061, p = 0.003). No correlation was found between PENK A level and urea (p = 0.192), eGFR (p = 0.922), dialysis vintage (p = 0.637), and residual urine output (p = 0.784). Heart failure (p = 0.961), EF (p = 0.361), and NT-proBNP (p = 0.949) were not associated with increased PENK A concentration. PENK A does not reflect renal function and cardiac status in patients with ESKD. Further research is required to establish the clinical utility of the new biomarker in patients with impaired kidney function.

Nonsteroidal Mineralocorticoid Receptor Antagonist (Finerenone) in Cardiorenal Disease.

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone's efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors' (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease.

Incidence and individual risk prediction of post-COVID-19 cardiovascular disease in the general population: a multivariable prediction model development and validation study.

Previous studies suggest relatively increased cardiovascular risk after COVID-19 infection. This study assessed incidence and explored individual risk and timing of cardiovascular disease occurring post-COVID-19 in a large primary care database. Data were extracted from the UK's Clinical Practice Research Datalink. Incidence rates within 180 days post-infection were estimated for arterial or venous events, inflammatory heart disease, and new-onset atrial fibrillation or heart failure. Next, multivariable logistic regression models were developed on 220 751 adults with COVID-19 infection before 1 December 2020 using age, sex and traditional cardiovascular risk factors. All models were externally validated in (i) 138 034 vaccinated and (ii) 503 404 unvaccinated adults with a first COVID-19 infection after 1 December 2020. Discriminative performance and calibration were evaluated with internal and external validation. Increased incidence rates were observed up to 60 days after COVID-19 infection for venous and arterial cardiovascular events and new-onset atrial fibrillation, but not for inflammatory heart disease or heart failure, with the highest rate for venous events (13 per 1000 person-years). The best prediction models had c-statistics of 0.90 or higher. However, <5% of adults had a predicted 180-day outcome-specific risk larger than 1%. These rare outcomes complicated calibration. Risks of arterial and venous cardiovascular events and new-onset atrial fibrillation are increased within the first 60 days after COVID-19 infection in the general population. Models' c-statistics suggest high discrimination, but because of the very low absolute risks, they are insufficient to inform individual risk management.