Impaired Ejection Fraction Research Articles

Independent risk factors of ejection fraction deterioration post discharge in hospitalized heart failure patients with mildly reduced ejection fraction

Abstract Background The identification of independent risk factors for left ventricular ejection fraction (LVEF) deterioration is of clinical importance in patients diagnosed heart failure with mildly reduced ejection fraction (HFmrEF). This study aimed to determine the independent risk factors of LVEF deterioration post discharge among hospitalized HFmrEF patients. Methods This retrospective study analyzed data from 807 HFmrEF patients admitted to our hospital between January 2015 and August 2020. LVEF values were assessed by echocardiography between 6 months and 1 year after discharge. Patients were followed up to a mean of 33 months. The primary endpoint was disease progression expressed as heart failure with reduced ejection fraction (HFrEF) between 6 months and 1 year post discharge. The secondary endpoint was all-cause death. Multivariate logistic regression analysis was conducted to identify independent risk factors associated with LVEF deterioration. Results There were 225 patients progressed to HFrEF between 6 months and 1 year post discharge. All-cause death was significantly higher in HFrEF patients (43%) compared to patients with stable LVEF (unchanged or improved, 24%, P<0.001). Multivariate logistic regression analysis showed that the independent risk factors associated with worsening LVEF in patients with HFmrEF were: female (OR=1.71, 95% CI 1.14 to 2.57, P=0.009), higher NT-proBNP (≥2312 pg/ml, OR=1.71, 95% CI 1.14 to 2.57, P=0.010), higher uric acid (≥318 µmol/L, OR=11.63, 95% CI 7.89 to 17.15, P<0.001), and larger end-diastolic left ventricular dimension (OR=1.05, 95% CI 1.02 to 1.08, P<0.001). Conclusion Results of this study might help risk stratification to identify hospitalized HFmrEF patients with increased risk of progression to HFrEF post discharge. Patients with above clinical features should undergo more intensively monitoring and enhance care adherence to HF guideline medications. Future studies are needed to validate if tailored guideline adherence management strategies for post-discharged HFmrEF patients based on personalized risk stratification could mitigate LVEF progression and improve survival of these patients.

Pregnancy and inherited cardiomyopathies: insights from specialized care

Abstract Background Pregnancy and postpartum represent periods of increased risk of cardiovascular complications. Management of women with modified World Health Organization (mWHO) class II–III, III, and IV during pregnancy and around delivery should be conducted at an expert centre by a multidisciplinary team. Purpose Our objective was to analyze the impact of pregnancy on cardiomyopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom. Methods All women with cardiomyopathy referred due to pregnancy to our centre between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected. Results Between 2016 and 2023, follow-up and delivery planning were initiated for 86 pregnancies in women with cardiomyopathies referred to our centre, resulting in 81 live births and 5 miscarriages, all in the first trimester. Among the full-term pregnancies, 17 (21%) were in patients in mWHO class I or II, 22 (27.2%) in II-III, 34 (42%) in III, and 8 (9.8%) in IV. The distribution of cardiomyopathy types among different mWHO classification is represented in Table 1. Women in mWHO class ≥ II-III had more pregnancy-related events than patients in mWHO I or II [28 (34.6%) vs 1 (1.2%); p = 0.004]. The most common complication in the first group was supraventricular tachycardia in 11 pregnancies (13.6%), followed by gestational diabetes in 9 (11.1%), left ventricular ejection fraction impairment in 4 (4.9%), preeclampsia in 3 (3.7%), and 1 (1.2%) ventricular tachycardia. One patient in the second group developed gestational diabetes. The distribution of the type of delivery among different mWHO classification is represented in Table 2. Only one patient with hypertrophic cardiomyopathy in mWHO II-III who underwent a caesarean section presented a post-delivery complication related to retroperitoneal haematoma, with no statistical significative differences between the groups (p = 0.604). 100% of the patients survived pregnancy and postpartum period. Conclusions Pregnant women with cardiomyopathy face an increased risk of adverse events. Despite the presence of cardiovascular and obstetric complications, careful monitoring at a specialized centre leads to favourable outcomes particularly concerning mortality rates for both the mother and fetus. This highlights the importance of a comprehensive risk assessment and meticulous pregnancy and delivery planning to ensure optimal maternal and fetal health.Table 1.Cardiomyopathy and mWHOTable 2.Type of delivery and mWHO

Clinical, laboratory, and echocardiographic characteristics of critical multisystem inflammatory syndrome in children: a retrospective, observational study

ObjectiveMultisystem inflammatory syndrome in children (MIS-C) is a critical childhood disease that is associated with coronavirus disease (COVID-19). We aimed to describe the clinical, laboratory, and echocardiographic characteristics and outcome of critical MIS-C cases in Egyptian children during the first wave of the COVID-19 pandemic.DesignA retrospective, observational study.SettingA single-center tertiary pediatric intensive care unit (PICU).In Ain Shams university hospitals Cairo EgyptMethodsChildren admitted to the PICU diagnosed with severe MIS-C as per the Centers for Disease Control’s definition from June 23, 2020, to August 22, 2020, were included.ResultsThe patient’s mean age was 7.45 (interquartile range [IQR], 4.23) years, and the cause of PICU admission was hypotension and shock. All patients had a fever for 4.8 (IQR, 2.5) days before shock developed. Overall, 68% had a gastrointestinal manifestation, and 55.6% had a rash. Thirty-five of 45 patients had ≥ 4 elevated inflammatory markers. The cardiac troponin I level was elevated in 35 of 45 patients. The most common cardiac condition was valvulitis (tricuspid regurgitation, 29/45; mitral valve regurgitation, 28/45; pulmonary valve regurgitation, 5/45; atrial valve regurgitation, 4/45). Twenty-one patients had an impaired ejection fraction < 50%, and 17 patients had coronary dilatation. Six patients had pericardial effusion, 1 patient had dilated pulmonary arteries, and 6 patients (13.3%) died of their associated comorbidities. The mean PICU length of stay among patients with no associated comorbidities was 7 days.ConclusionsCritical cases of MIS-C had a spectrum of different cardiac conditions, with valvulitis being the most common one. The worst outcome occurred in patients with comorbidities and infants.

Incidence of Myocarditis among Patients Recovered from COVID-19 Identified using Cardiac Magnetic Resonance: A 1-year Single-centre Retrospective Study

Background: COVID-19 continues to engender significant morbidity and mortality globally and is associated with cardiac injuries, such as myocarditis. This study reports the incidence of myocarditis identified using cardiac magnetic resonance (CMR) in patients recovered from COVID-19. Methods: This is a single-centre retrospective cohort study conducted among recovered COVID-19 patients who underwent CMR from 1 January 2020 to 31 December 2021. Results: Most patients with evidence of myocardial oedema on CMR had a mild-type infection (31 of 54 [57%]), with dyspnoea (15 [28%]) and palpitations (12 [22%]) being the most common symptoms. Twenty-nine of 54 (54%) patients had increased T2 signal indicative of myocarditis; eight (28%) of them had evidence of myocardial fibrosis on late gadolinium enhancement primarily located at the lateral walls with sub-epicardial and mid-wall involvement dispersed in the basal to apical segments. Myocardial oedema was noted in nine (31%) patients. Six (20%) of them had an impaired left ventricular ejection fraction of &lt;50% and three patients (10%) had an impaired right ventricular ejection fraction of &lt;50%. There was no significant difference in left ventricular (57% versus 61%; p=0.13) and right ventricular (57% versus 60%; p=0.51) systolic function between the two groups. Conclusion: Myocarditis after COVID-19 can be a lasting consequence, and CMR may serve as a sensitive imaging tool to investigate any suspected cardiac injury after treatment of the infection. The findings of the study may aid in determining the other possible long-term effects in patients who have recovered from COVID-19, particularly those who continue to experience symptoms.

Real-world experience in initiation of treatment with the selective cardiomyosin inhibitor mavacamten in an outpatient clinic cohort during the 12-week titration period.

Lately, mavacamten emerged as a new therapeutic option for symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Clinical trials revealed reduction of serum biomarkers, and left ventricular outflow tract (LVOT) obstruction, as well as an improvement in clinical symptoms and exercise capacity. Nevertheless, clinical experience and manageability of patients in a real-world setting is still lacking. 22 patients with symptomatic oHCM (54.5% male, age 58.5 ± 16.2years) and elevated LVOT gradients were started on mavacamten between March 2023 and June 2024. All patients were New York Heart Association (NYHA) class II or higher. Seven patients were excluded from primary analysis due to comedication with Angiotensin-converting-enzyme-inhibitors or Angiotensin-II receptor blockers. Cardiac imaging, laboratory work-up and clinical evaluation were assessed at three visits during the 12weeks initiation phase; Dosing of mavacamten was adjusted according to manufacturer's recommendations. At 12weeks, the majority of patients described a significant improvement of their quality of life. Work-up at 12weeks revealed a significant reduction of serum biomarkers and LVOT gradients. In four patients, mavacamten needed to be temporarily paused due to clinical complaints or transient left ventricular ejection fraction deterioration below 50% with subsequent full recovery. We provide first insights into the usage of mavacamten in oHCM patients during the titration period in a real-world setting. Clinical findings are in line with previous clinical trials. In accordance with current recommendations, we highlight the need for standardized follow-up of patients on mavacamten treatment.

Expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO in Relation to Left Ventricular Remodeling in Patients Six Months after the First Myocardial Infarction: A Prospective Study.

Background: After myocardial infarction (MI), adverse left ventricular (LV) remodeling may occur. This is followed by LV hypertrophy and eventually heart failure. The remodeling process is complex and goes through multiple phases. The aim of this study was to investigate the expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO, each involved in a specific step of LV remodeling, in association with the change in the echocardiographic parameters of LV structure and function used to assess the LV remodeling process in the peripheral blood mononuclear cells (PBMCs) of patients six months after the first MI. The expression of selected genes was also determined in PBMCs of controls. Methods: The study group consisted of 99 MI patients, who were prospectively followed-up for 6 months, and 25 controls. Cardiac parameters, measured via conventional 2D echocardiography, were evaluated at two time points: 3-5 days and 6 months after MI. The mRNA expression six-months-post-MI was detected using TaqMan® technology (Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA). Results:HMGB1 mRNA was significantly higher in patients with adverse LV remodeling six-months-post-MI than in patients without adverse LV remodeling (p = 0.04). HMGB1 mRNA was significantly upregulated in patients with dilated LV end-diastolic diameter (LVEDD) (p = 0.03); dilated LV end-diastolic volume index (LVEDVi) (p = 0.03); severely dilated LV end-systolic volume index (LVESVi) (p = 0.006); impaired LV ejection fraction (LVEF) (p = 0.01); and LV enlargement (p = 0.03). It was also significantly upregulated in PBMCs from patients compared to controls (p = 0.005). TGF-β1 and BIRC3 mRNA were significantly lower in patients compared to controls (p = 0.02 and p = 0.05, respectively). Conclusions: Our results suggest that HMGB1 is involved in adverse LV remodeling six-months-post-MI, even on the mRNA level. Further research and validation are needed.

Correlation between mitral annular plane systolic excursion (MAPSE) at different degrees of ejection fraction in patients with diabetes mellitus

Background and aim. Diabetic cardiomyopathy is characterized by myocardial structure and function abnormality in the absence of other cardiovascular risk factors. Early detection of cardiac dysfunction is crucial for timely intervention and improved patient outcomes. The purpose of this study is to determine how mitral annular plane systolic excursion (MAPSE) is a sensitive marker of early cardiac dysfunction in patients with diabetes mellitus by examining the relationship between MAPSE values and different levels of ejection fraction. Methods and material. An analytical cross-sectional study was carried out at Dr. Wahidin Sudirohusodo Hospital in Indonesia's Integrated Heart Center. The sample included 79 patients with ages from 18 to 65 years old and a type 2 diabetes diagnosis. Data collected included age, gender, ejection fraction, and MAPSE. Statistical methods included descriptive analysis and Spearman correlation tests. Results. The study population was predominantly male (71%), with a mean age of 55.5 years for those without EF impairment and 59.5 years for those with impairment. The average impaired EF was 37.69%. MAPSE examination in septal, lateral, and average segments showed significant differences. There is a strong positive association between MAPSE and EF in all study samples. In patients with preserved EF (average EF 58%), MAPSE was 14.4 mm, and in those with reduced EF (average EF 29%), MAPSE was 6.31mm, with significant positive correlations. No significant results were observed in subjects with mid-range EF. Conclusions. This research revealed that mitral annular plane systolic excursion (MAPSE) is significantly associated with ejection fraction (EF) in individuals with diabetes mellitus (DM), mainly when EF is either well-maintained or diminished.

Heart Rate Variability and Global Longitudinal Strain for Prognostic Evaluation and Recovery Assessment in Conservatively Managed Post-Myocardial Infarction Patients.

Background: Heart rate variability (HRV) is the fluctuation in the time intervals between adjacent heartbeats. HRV is a measure of neurocardiac function that is produced by dynamic autonomic nervous system (ANS) processes and is a simple measure that estimates cardiac autonomic modulation. Methods: The study included 108 patients admitted to the Coronary Intensive Care Unit with acute myocardial infarction (AMI) who did not undergo primary percutaneous transluminal coronary angioplasty (PTCA) or systemic thrombolysis and followed conservative management. All patients underwent detailed clinical, biological, and paraclinical assessments, including evaluation of HRV parameters and echocardiographic measurements. The analysis of RR variability in both time and frequency domains indicates that the negative prognosis of patients with AMI is associated with an overall imbalance in the neuro-vegetative system. The HRV parameters were acquired using continuous 24 h electrocardiogram (ECG) monitoring at a baseline, after 1 month, and 6 months. Results: Our analysis reveals correlations between alterations in HRV parameters and the increased risk of adverse events and mortality after AMI. The study found a significant improvement in HRV parameters over time, indicating better autonomic regulation post-AMI. The standard deviation of all RR intervals (SDNN) increased significantly from baseline (median 75.3 ms, IQR 48.2-100) to 1 month (median 87 ms, IQR 55.7-111) and further to 6 months (median 94.2 ms, IQR 67.6-118) (p < 0.001 for both comparisons). The root mean square of successive difference of RR (RMSSD) also showed significant increases at each time point, from baseline (median 27 ms, IQR 22-33) to 1 month (median 30.5 ms, IQR 27-38) and from 1 month to 6 months (median 35 ms, IQR 30-42) (p < 0.001 for all comparisons), indicating enhanced parasympathetic activity. Moreover, changes in HRV parameters have been associated with impaired left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS), indicating a relationship between autonomic dysfunction and myocardial deformation. GLS values improved from a baseline median of -11% (IQR 5%) to -13% (IQR 4%) at 6 months (p < 0.001), reflecting better myocardial function. Conclusions: HRV parameters and cardiac performance analysis, especially using GLS, offer a solid framework for evaluating recovery and predicting adverse outcomes post-MI.

Abstract Tu050: Deficiency Of Mitochondrial Disulfide Relay Carrier Leads To Cardiac Hypertrophy

Background: Innate immune activation is critical for cardiac hypertrophy; however, its upstream regulation is less well understood. Coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4) is an essential carrier for the import of various mitochondrial proteins including TP53 -regulated inhibitor of apoptosis 1 (TRIAP1). CHCHD4 was recently identified as a dysregulated gene in patients with dilated cardiomyopathy and was separately found to mediate innate immune signaling in skeletal muscle. Therefore, we hypothesized that CHCHD4 may play a role in the development of cardiac hypertrophy by regulating innate immunity. Methods: Genetically modified C57BL/6 mice overexpressing CHCHD4 (CHCHD4 Tg) or haploinsufficient in CHCHD4 ( CHCHD4 +/- ) were utilized. Mice were injected either with low dose (2 mg/kg) or high dose (30 mg/kg) isoproterenol (ISO) daily for up to 3 wk to induce hypertrophy. Results: CHCHD4 +/- mice developed cardiac hypertrophy (HW/BW (mg/g): 3.62 ± 0.15 CHCHD4 +/- vs 2.70 ± 0.13 wild-type (WT) or 2.55 ± 0.16 CHCHD4 Tg, p&lt;0.0001) when allowed to age to 28 wk and showed reduced left ventricular ejection fraction (EF) at 1 year when compared with wild-type or CHCHD4 Tg mice (EF (%): 50.94 ± 0.94 CHCHD4 +/- vs 58.33 ± 0.78 wild-type or 57.88 ± 1.32 CHCHD4 Tg, p&lt;0.0001). After low dose ISO treatment, CHCHD4 +/- mice had reduced EF at 2 wk compared to WT or CHCHD4 Tg mice (EF (%): 44.60 ± 1.74 CHCHD4 +/- vs 54.28 ± 0.86 wild-type, p&lt;0.0001; or vs 52.76 ± 1.33 CHCHD4 Tg, p=0.0006). After high dose ISO treatment, WT mice developed cardiac hypertrophy by 1 wk and impaired EF by 3 wk, while CHCHD4 Tg mice remained normal. ISO treatment caused reduction of CHCHD4 levels in both the 24 hr and 1 wk states. This reduction was associated with decreased TRIAP1 and activation of the cGAS-STING-NFkB pathway in wild-type, but not CHCHD4 Tg mice. Further, plasma mitochondrial DNA (mtDNA) was 2.3 times higher in WT mice treated with high dose ISO for 1 wk compared to WT control (n=8-11/group, p=0.011), while that of CHCHD4 Tg mice was not significantly changed by ISO treatment. Conclusions: Our findings suggest that CHCHD4 may be a key upstream regulator of innate immune activation mediating cardiac hypertrophy and that cell-free mtDNA in blood could be a potential biomarker of pathogenesis.

Hypertension and its association to phenotype on left ventricular function in hypertrophic cardiomyopathy patients assessed by cardiovascular magnetic resonance imaging

Hypertension and its association to phenotype on left ventricular function in hypertrophic cardiomyopathy patients assessed by cardiovascular magnetic resonance imaging

Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T‐786C, G894T, and INTRON variable number of the tandem repeat functional interaction

AbstractBackgroundCardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.ObjectivesExploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high‐risk cardiovascular disease patients.Materials and methodsPatients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T‐786C), genotyped by fluorescence polarization assays, were registered. The 27‐bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction‐restriction fragment length polymorphism. Association analyses were run with the R‐3.2.0 software.ResultsA significant association between endothelial nitric oxide synthase 786‐TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3‐months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function‐Erectile Function 21 ± 10 scores, p &lt; 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p &lt; 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894‐T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.ConclusionsOur study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high‐risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease.

Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1β and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.

Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR

BackgroundThe optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. Trial designThe objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. ConclusionThe ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.

Evaluation of Serum Myostatin Concentration in Chronic Heart Failure with Preserved and Impaired Left Ventricular Ejection Fraction.

Background: Chronic heart failure (CHF) is a complex clinical syndrome associated with muscle wasting, which can progress to cardiac cachexia. Myostatin, a negative regulator of muscle growth, has been implicated in the pathophysiology of muscle wasting in CHF patients and suggested as a potential biomarker. The objective of this study was to investigate serum myostatin concentration in patients with CHF with preserved and reduced ejection fraction. Methods: The authors conducted a single-centre study comparing serum myostatin levels, functional and echocardiographic parameters, muscle mass, strength and function in patients with CHF to a control group without CHF. The study group was further divided into sub-groups with preserved and reduced or mildly reduced ejection fraction. Results: Results showed no significant differences in myostatin concentration between CHF patients and controls, and no correlation with sarcopenia or dynapenia. However, a higher myostatin concentration was found in patients with impaired systolic function (Me = 1675 pg/mL vs. Me-884.5 pg/mL; p = 0.007). A positive correlation between myostatin concentration and muscle mass (r = 0.27; p = 0.04), and functional parameters such as Norton (r = 0.35; p < 0.01), I-ADL (r = 0.28; p = 0.02) and Barthel scale (r = 0.27; p = 0.03) scores, was also observed. Conclusions: Myostatin appears to play a role in muscle wasting and its progression to cardiac cachexia in patients with impaired ejection fraction. Further research is needed to confirm these findings and explore myostatin's potential as a biomarker for muscle loss and a target for pharmacotherapeutic agents in this population of patients.

Peripheral Arterial Disease in the Context of Acute Coronary Syndrome: A Comprehensive Analysis of Its Influence on Ejection Fraction Deterioration and the Onset of Acute Heart Failure.

Peripheral artery disease is a condition that causes narrowing of the arteries, impairing circulation to the extremities. Globally, it affects millions of people and is more prevalent in older adults and those with diabetes, high blood pressure, or high cholesterol. There is an overlap specific to polyvascular patients, and almost 50% of patients with PAD have coronary artery disease. Compelling evidence reveals a noteworthy association between PAD and major adverse cardiovascular events (MACEs) in individuals experiencing acute coronary syndrome (ACS) but limited knowledge exists regarding the influence of PAD on left ventricular systolic function during ACS. In a retrospective case-control study, we examined 100 participants who presented with ACS (mean age = 61.03 years, 80 [80%] males). The patients were divided into two groups: the ACS-PAD group (32 subjects, 74% of them with STEMI, 10% with NSTEMI, and 16% with NSTEACS) and the ACS-nonPAD group (68 participants). This study highlighted that PAD negatively impacts patients with non-ST-segment elevation myocardial infarction (NSTEMI). These patients were likely to experience a decline of approximately 19.3% in their left ventricular ejection fraction (LVEF) compared to the ACS-nonPAD group (p = 0.003) and presented a worse clinical status (the PAD group correlated with Killip class IV, p = 0.049). Our analysis indicates that patients diagnosed with NSTEACS and PAD tend to have a higher LVEF of over 55% and a lower HEART score. Patients with PAD tend to have a functionally higher EF but clinically present with more unstable scenarios (pulmonary edema and cardiogenic shock). This is mainly driven by a higher prevalence of HFpEF in the PAD group. Looking closer at the PAD group, they have a higher incidence of comorbidities such as diabetes, hypertension, high cholesterol, CAD, and stroke, as well as being more active smokers.

Renal function improvement correlates with 3D echocardiographic findings: Effect of surgical mitral valve repair.

The association between surgical treatment of mitral regurgitation (MR) and renal function is not sufficiently well-known. We tried to evaluate renal function before and after the procedure of surgical mitral valve repair (SMVR) in degenerative severe MR. Patients with primary severe (4+) MR and normal left ventricular ejection fraction (LVEF) that underwent SMVR, examined by a cutting-edge 3-dimensional (3D) echocardiographic probe were enrolled in this study. We took three CKD-EPI equations to measure estimated glomerular filtration rate (eGFR) before SMVR and shortly before patients discharge. A total of 40 patients with baseline lower mean eGFR were evaluated. Measurements substantiated statistically significant improvements in eGFR (p < 0.001), multivariable linear regression modeling indicating prominent associations between increase in eGFR and decrease of MR (p = 0.003), decline of pulmonary arterial systolic pressure (p = 0.018), as well as increment of forward stroke volume (p = 0.02), in spite of LVEF reduction, left ventricular global longitudinal strain worsening and left atrial ejection fraction impairment. Renal function improves after SMVR in patients with degenerative significant MR and preserved LVEF, regardless of cardiac functional worsening.

Analyzing Short and Medium-Term Morbidity and Mortality in Patients with Heart Failure and Borderline Ejection Fraction (EF: 40-49%).

Introduction: Heart failure with moderately impaired ejection fraction (HFmEF) has garnered increasing attention in recent years. However, understanding this new phenotype, particularly concerning morbidity and mortality, remains limited. Materials and Methods: A prospective, observational, and single-center study spanning 26 months was conducted on 204 patients with HFmEF selected from 447 patients with chronic heart failure (CHF) categorized based on their left ventricular ejection fraction (LVEF): HF with reduced ejection fraction (HFrEF) if LVEF ≤ 40% (n = 173) and HF with preserved ejection fraction (HFpEF) if LVEF ≥ 50% (n = 70). This study included a detailed evaluation of factors precipitating cardiovascular (CV) death and rehospitalizations in patients with HFmEF. Results: After a mean follow-up of 431 days in the HFmEF patient group, our results indicated that CV mortality at six months was 2.5%, and at one year, it was 5.9%. Prognostic factors for survival included chronic kidney disease, blood glucose level &gt; 1.4g/l, presence of moderate to severe secondary mitral insufficiency, sphericity index &lt; 1.7, elevated pulmonary vascular resistance, and resistance to diuretic treatment. HF rehospitalization rates at 6 and 12 months were 2.5% and 8.3%, respectively. Predictive factors for HF rehospitalizations included diabetes, hemoglobin level &lt; 13g/dl, left atrial volume &gt; 34 ml/m3-, mitral S-wave &lt; 0.05cm/s, non-improvement of global longitudinal strain, and resistance to diuretic treatment. Conclusion: This category of HF remains underrecognized and neglected by practitioners, and its prognosis is formidable, especially in the presence of adverse prognostic factors.

Low body mass index is associated with adverse cardiovascular outcomes following PCI in India: ACC-NCDR registry

ObjectiveRegistry-based prospective study was conducted to evaluate association of body mass index (BMI) with major adverse coronary events (MACE) following percutaneous coronary intervention (PCI). MethodsSuccessive patients undergoing PCI were enrolled from April‘19 to March’22 and classified into five BMI categories (<23.0,23.0-24.9,25.0-26.9,27.0–29.9, and ≥30.0 kg/m2). Clinical, angiographic features, interventions and outcomes were obtained by in-person or telephonic follow-up. Primary endpoints were (a) MACE(cardiovascular deaths, acute coronary syndrome or stroke, revascularization, hospitalization and all-cause deaths) and (b)cardiovascular deaths. Cox-proportionate hazard ratios(HR) and 95 % confidence intervals(CI) were calculated. ResultsThe cohort included 4045 patients. Mean age was 60.3 ± 11y, 3233(79.7 %) were men. There was high prevalence of cardiometabolic risk factors. 90 % patients had acute coronary syndrome(STEMI 39.6 %, NSTEMI/unstable angina 60.3 %), 60.0 % had impaired ejection fraction(EF) and multivessel CAD. Lower BMI groups (<23.0 kg/m2) had higher prevalence of tobacco use, reduced ejection fraction(EF), multivessel CAD, stents, and less primary PCI for STEMI. There was no difference in discharge medications and in-hospital deaths. Median follow-up was 24 months (IQR 12–36), available in 3602(89.0 %). In increasing BMI categories, respectively, MACE was in 10.9,8.9,9.5,9.1 and 6.8 % (R2 = 0.73) and CVD deaths in 5.1,4.5,4.4,5.1 and 3.5 % (R2 = 0.39). Compared to lowest BMI category, age-sex adjusted HR in successive groups for MACE were 0.89,0.87,0.79,0.69 and CVD deaths 0.98,0.87,0.95,0.75 with overlapping CI. HR attenuated following multivariate adjustments. ConclusionsLow BMI patients have higher incidence of major adverse cardiovascular events following PCI in India. These patients are older, with greater tobacco use, lower EF, multivessel CAD, delayed STEMI-PCI, and longer hospitalization.

Lisocabtagene Maraleucel in Relapsed/Refractory Large B-Cell Lymphoma: Real World Analysis from the Cell Therapy Consortium

Introduction Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR T cell therapy approved for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the TRANSCEND (Abramson et al, Lancet 2020), TRANSFORM (Kamdar et al, Lancet 2022), and PILOT studies (Sehgal et al, Lancet Oncol 2022). Extending clinical trial results for liso-cel to the real-world setting, we performed a multicenter retrospective study to evaluate the safety and efficacy of liso-cel in standard of care practice. Methods Patients (pts) aged ≥18 years with LBCL who received commercial liso-cel infusion between February 2021 (time of FDA approval) and June 2023 at 7 academic US medical centers were identified from the Cell Therapy Consortium registry. Pt and treatment characteristics were summarized descriptively, and the Kaplan Meier method was used for survival outcomes. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria. Tumor response was assessed per Lugano criteria locally by the treating clinician. Results As of 6/10/2023, 101 pts underwent liso-cel infusion. Detailed baseline pt characteristics are shown in Table 1. Median age at apheresis was 71 years (range: 30-85) with 35% of pts ≥75 years, 60% were male, 16% had an ECOG PS of ≥2 at apheresis, and 11% had active secondary CNS involvement. By histology, 86% of pts had DLBCL, 7% HGBL, 5% TFL, and 2% PMBCL. Baseline comorbidities included diabetes (18%), stage IV chronic kidney disease (5%), cerebrovascular disease (5%), impaired cardiac ejection fraction (2%), pulmonary dysfunction (2%), impaired hepatic function (2%), and active infection (3%), with 68% having a Charlson Comorbidity Index score of ≥3. Due to comorbidities, 30% of pts would have been ineligible for the TRANSCEND clinical trial. The median number of prior therapies was 3 (range: 1-8) and 16% of pts underwent prior autologous stem cell transplant. Bridging therapy was used in 62% of pts including 41% receiving polatuzumab-based treatment, 24% chemoimmunotherapy, and 21% radiation therapy. Seven (7%) pts received liso-cel on an expanded access trial (NCT04400591) due to a non-conforming product. Median time from apheresis to CAR T-cell infusion was 39 days (IQR: 34-43) and 85% of CAR T-cell infusions occurred inpatient. Any Grade CRS occurred in 49% (3% were Grade ≥3) and any Grade ICANS occurred in 26% (10% were Grade ≥3). Median onset of CRS and ICANS was 4 and 6 days following liso-cel infusion, respectively. Tocilizumab was administered in 31% and 31% of pts received steroids for toxicity management. Nine deaths (9%) unrelated to lymphoma progression occurred at a median of 1.2 months (range: 0.3-4.3) with 2 due to infectious complications, 2 due to other malignancy, 1 due to grade 5 neurologic toxicity, 1 due to concurrent grade 5 neurologic toxicity and grade 5 CRS, 1 due to accidental death, and 2 due to unknown causes. The 6-month incidence of non-relapse mortality was 8% (95% CI, 3.4% - 15%). The overall response rate (ORR) to bridging therapy, as assessed prior to lymphodepletion, was 45% with 17% achieving a complete response (CR). Following liso-cel infusion, response assessment was performed at day 30 and/or day 90 according to treating center practice, or in those determined to have clinical progression. Of the 89 pts evaluable at day 30, the ORR was 81% with 63% achieving a CR. Among 76 pts evaluable at day 90, the ORR was 63% with 58% achieving a CR. With a median follow-up of 10.3 months (range 0.3-22.8), month 6 outcomes were 62.7% (95% CI, 52.8% - 74.3%) for progression-free survival, 71.6% (95% CI, 60.9% - 84.1%) for duration of response, and 77.1% (95% CI, 68.4% - 86.9%) for overall survival ( Figure 1). Conclusions These analyses confirm that efficacy and safety are similar or superior to those of patients enrolled in liso-cel prospective clinical trials for R/R LBCL. Notably, these outcomes were achieved in pts predominately of advanced age and with a significant comorbid burden, recognizing that one-third would have been ineligible for TRANSCEND. These results also likely reflect advancements in patient selection and toxicity management including the real world utilization of novel bridging therapy to temporize and debulk disease. Follow-up is ongoing and updated data will be presented at the meeting.

Insuffisance cardiaque aiguë à fraction d’éjection altérée : signes électrocardiographiques associés à la mortalité à l'institut de cardiologie d'Abidjan

IntroductionHeart failure with impaired ejection fraction (HFIEF) represents the end-stage of most cardiac diseases, and is responsible for a high mortality rate. In order to identify patients at risk, numerous clinical and paraclinical prognostic factors have been proposed. The electrocardiogram (ECG), easy to perform and inexpensive, retains a powerful role in the prognostic evaluation of heart failure patients. The aim was to evaluate ECG signs associated with mortality in a retrospective cohort of patients with ICFEA. MethodologyThe study was observational and analytical based on retrospective data collected from patients benefiting from a primary hospitalization for ICFEA at the Abidjan Heart Institute from January 2018 to July 2020. ResultsOf the 370 patients included, 197 had died by August 1, 2020, representing an overall mortality of 53%. Mortality progressed gradually up to one year, then remained unchanged up to 30 months.In multivariate Cox regression including ECG variables only, the presence of intra-ventricular conduction disorders (OR: 1.80; 95% CI [1.01–3.25]), microvoltage (OR: 1.82; 95% CI [1.05–16]), and pathological Q waves (OR: 1.70; 95% CI [1.02–2.83]), were significantly associated with overall mortality. When ECG variables and clinical, paraclinical and therapeutic demographic variables were included, only the presence of pathological Q waves (OR:1.74; 95% CI [1.01–3.01]) persisted as a risk factor for mortality. Hypertension and treatment of heart failure, in particular ACEI/ARII, beta-blockers and ARM, were protective factors. The presence of Q waves was associated with a significant reduction in survival, based on curves obtained using the Kaplan-Meier model. ConclusionICFEA is responsible for high mortality, mainly in the year following the 1st hospitalization for cardiac decompensation. The presence of pathological Q waves is the only electrocardiographic sign that remains statistically associated with a poor prognosis, after adjustment.