Impaired Left Ventricular Ejection Fraction Research Articles

Corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis stratified by left ventricular ejection fraction.

This study aimed to investigate the relationship between corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis, stratified by left ventricular ejection fraction (LVEF) at diagnosis. This study conducted a post hoc analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis, a retrospective multicentre registry. Cardiac sarcoidosis was diagnosed based on the 2016 Japanese Circulation Society and 2014 Heart Rhythm Society criteria. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and fatal ventricular arrhythmia events. Patients were divided into three groups based on LVEF: preserved LVEF (≥50%, n = 251), moderately impaired LVEF (LVEF, 35-49%; n = 149), and severely impaired LVEF (<35%, n = 99). Among 499 patients with cardiac sarcoidosis (mean age: 61.6 ± 11.4 years, male: 36.1%), 419 (84.0%) were treated with corticosteroids after diagnosis. During a median follow-up of 33.7 months (interquartile range, 16.8-62.7 months), 144 primary endpoints (28.9%) occurred. Corticosteroid therapy was associated with better prognosis when assessed in terms of primary endpoint in the entire cohort [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.89, P = 0.010]. When stratified by LVEF, corticosteroid therapy was significantly associated with a lower incidence of primary endpoints in the preserved LVEF group (HR, 0.30; 95% CI, 0.15-0.57, P < 0.001), but not in the moderately and severely impaired LVEF groups. This association remained robust, even after adjusting for confounders. In this large cohort of cardiac sarcoidosis, corticosteroid therapy was associated with a lower incidence of long-term outcomes only in patients with preserved LVEF at diagnosis. UMIN000034974.

An Observational Study on the Reversibility of Left Ventricular Diastolic Dysfunction, Impaired Left Ventricular Ejection Fraction and Abnormal Left Ventricular Mass with Levothyroxine Replacement in Primary Hypothyroid Patients of Indian Origin

An Observational Study on the Reversibility of Left Ventricular Diastolic Dysfunction, Impaired Left Ventricular Ejection Fraction and Abnormal Left Ventricular Mass with Levothyroxine Replacement in Primary Hypothyroid Patients of Indian Origin

Absolute blood volume and long-term survival in chronic hemodialysis patients.

Current online hemodiafiltration devices can be used to determine the absolute blood volume in clinical practice using the dialysate bolus method. Most of publications on this method have focused on preventing intradialytic complications. The influence of absolute blood volume on long-term prognosis has not been reported yet. A total of 79 participants in a previous study about absolute blood volume were followed for 5 years. Patients with a specific blood volume above (n = 45) and below 75 ml/kg (n = 34) respectively were compared with regard to survival using Kaplan-Meier analysis. Patients with a specific blood volume below 75 ml/kg had a significantly higher overall 5-year survival rate than patients above 75 ml/kg (70% vs 39%, p = 0.0233). In patients without cardiac dysfunction, there were no significant differences in 5-year survival between a specific blood volume below or above 75 ml/kg (66% vs 51%). A specific blood volume above 75 ml/kg was associated with an increased mortality in patients with mildly impaired left-ventricular systolic ejection fraction of 40%-59%, whereas in patients with normal blood volume this cardiac impairment did not impact mortality (22% vs 90% 5-year survival, p = 0.0036). This demonstrates the significance of optimum volume control for long-term survival particularly in cases of reduced cardiac function.

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&amp;lt;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&amp;lt;0.001), and larger end-diastolic left ventricular dimension (OR=1.05, 95% CI 1.02 to 1.08, P&amp;lt;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.

Acetazolamide for patients with acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials

Abstract Background The role of acetazolamide as an adjunct to standard loop diuretic therapy in patients with acute decompensated heart failure (ADHF) remains uncertain. Purpose We undertook a systematic review and meta-analysis to ascertain the efficacy and safety of acetazolamide plus standard of care (SOC) in patients with ADHF. Methods In January 2024, we systematically searched PubMed, Embase, and Cochrane for randomised controlled trials (RCTs) comparing acetazolamide plus SOC versus SOC alone in patients with ADHF. Effective decongestion was defined as per the definition of each individual study. We pooled risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Statistical analyses were performed using Review Manager version 5.4.1. Results We included 4 RCTs comprising 634 patients, of whom 318 (50.1%) were randomised to acetazolamide plus SOC. The mean age was 77.1 years and 64.2% were male. Nearly half of the patients (n=320; 50.5%) had impaired left ventricular ejection fraction at baseline. Most patients had a New York Heart Association functional class III or higher, ranging from 75 to 91% in each study. In the pooled analysis, acetazolamide plus SOC significantly increased the proportion of patients with clinical decongestion at day 3 compared with SOC alone (RR 1.36; 95% CI 1.10 to 1.68; p=0.005; Figure 1A). There was no significant difference between groups in natriuresis at day 1 (SMD 0.46; 95% CI -0.01 to 0.94; p=0.06; Figure 1B) or worsening renal function (RR 1.71; 95% CI 0.73 to 3.98; p=0.22; Figure 1C). Conclusion In this meta-analysis of RCTs among patients admitted with ADHF, acetazolamide plus SOC significantly improved the proportion of patients with clinical decongestion at day 3 relative to SOC alone, without significantly affecting renal function or natriuresis.Figure 1

Unexpected macrophage-mediated myocardial cGas-STING activation in a novel mouse model of stress-related sleep disturbance

Abstract Background Delayed bedtime following stress disorder is prevalent in waves of pandemics and modern life. Considered to be a specific and important contributor to cardiovascular health, stress-related sleep disturbance has an unmet need in steady preclinical models. We previously found exciting corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH) area of mice could induce 3-hour-long wakefulness. Purpose This study aimed to induce reproducible phenotypes of stress-related sleep disturbance in mice and explore the potential impact on cardiac function. Methods The chemogenetic method of designer receptors exclusively activated by designer drugs (DREADD) system was adopted to mimic stress-related sleep disturbance. We transfected PVH CRH neurons with rAAV-hSyn-DIO-hM3Dq-mCherry and rAAV-Crh-CRE. Prolonged CRH neuron activation was induced by daily intraperitoneal injection of clozapine N-oxide (CNO, 3mg/kg) at 9 am. Bulk RNA-sequencing and bioinformatics analysis were conducted for mechanistic exploration. Results 2-week repeated chemogenetic activation of PVH CRH neurons induced a 5-fold corticosterone release, consistent with increased daily 3-hour wakefulness and corresponding decreases in both rapid eye movement (REM) as well as non-REM sleep. Over 30% of chronic CRH activation mice displayed difficulties in maintaining balance and experienced premature mortality. Mice subjected to prolonged CRH activation showed impaired left ventricular ejection fraction (67.9% versus 48.2%, p=0.0011), and a dilated appearance demonstrated by histological staining. Intriguingly, the number of circulating monocytes increased. Then, we performed bulk RNA-sequencing of heart and bone marrow from CRH-activated and control mice. Differential gene expression and gene set enrichment analysis (GSEA) indicated marked activation of interferon-beta-related pathways in both tissues. Cytosolic DNA-sensing pathway and related key effector genes (cGAS, Cxcl10, CCL5) were found up-regulated in the heart, while mitochondrial oxidative phosphorylation was suppressed. We adopted the CIBERSORT tool to estimate immune infiltration in heart tissues and characterized M1 macrophage as the main pro-inflammatory cell. Further, we screened a set of secreted factors and mediators, which might play active roles in inflamed hearts. Conclusion Taken together, we report a failing heart in a mouse model of stress-related sleep disturbance. The neuro-immune axis involvement and molecular mechanisms merit in-depth explorations.

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

The impact of pulmonary fibrosis on cardiac function in chronic obstructive pulmonary disease

Abstract Background Emerging evidence indicates the coexistence pulmonary fibrosis and emphysema in patients with Chronic Obstructive Pulmonary Disease (COPD). The effect of pulmonary fibrosis on cardiac structure and function in COPD patients remains unclear. Purpose This study aimed to examine the association between the degree of pulmonary fibrosis identified on Computed Tomographic (CT) imaging and echocardiographic measures of cardiac structure and function in individuals with COPD. Methods The study included 456 individuals with COPD, participating in a large prospective cohort study. Patients with available CT scans and echocardiograms were included. Local histogram-based assessments of lung density were utilized to determine the percentage of fibrosis. Fibrosis was defined based on the CT attenuation within the range of -600 and -250 Hounsfield units. The association between percent fibrosis and measures of cardiac structure and function were investigated by univariable and multivariable linear regression models. Multivariable adjustments included age, sex, body mass index (BMI), and smoking. In addition, restricted cubic splines were generated to visually present the relationship between the percentage of fibrosis and specific echocardiographic parameters. Results The mean age was 71 (± 8 years), 48% were female, and the median BMI was 27 kg/m2 (IQR: 22; 30kg/m2). The mean forced expiratory volume in 1 second as a percentage of the predicted value (FEV1pp) was 47% (±18%). The mean forced vital capacity of predicted value was 71% (± 19%). The median percentage of fibrosis in the cohort was 4.9% (IQR: 3.9; 6.0%). Patients were stratified into tertiles based upon fibrosis percentage. BMI, frequency of diabetes, and FEV1pp were increasingly positively associated with fibrosis. Furthermore, significant trends for echocardiographic measures found that the patients with the most extensive fibrosis were seen to have impaired left ventricular (LV) ejection fraction (LVEF), lower absolute global longitudinal strain (GLS), increased left atrial (LA) volume index (LAVi), and higher LV mass as compared to those with less significant fibrosis. There were no significant differences between tertiles of fibrosis and age or sex. In univariable linear regression, significant inverse associations between the percentage of fibrosis, LVEF, GLS, and tricuspid annular plane systolic excursion (TAPSE) were seen (Table). For LV mass index and LAVi, significant direct associations were found (Table). After adjusting for potential confounding factors, only GLS and LAVi remained associated with pulmonary fibrosis (Figure). Conclusion This study found that GLS and LA volume were significantly associated with the degree of pulmonary fibrosis, even after adjusting for confounding variables. This may suggest that fibrosis is primarily linked with impaired left-sided measures of cardiac structure and function.Linear Regression ModelsCubic Spline Curves

Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction

Abstract Background * Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2). * Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools. * Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4). Purpose We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality. Method * A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up). * Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time. * An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG. * Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1). * The study was approved by the UK Health Research Authority (reference 21/LO/0051). Results * The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White. * Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p &amp;lt; 0.005), primarily driven by increased mortality (23% vs. 9.6%; p &amp;lt; 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p &amp;lt; 0.0001) – Figure 2. * AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p &amp;lt; 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01). * Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p &amp;lt; 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p &amp;lt; 0.0001; aHR 1.53, 95% CI 1.00 – 2.36). Conclusion An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF. Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.

Effects of empagliflozin on cardio-renal interaction in heart failure with reduced ejection fraction: results from in-vivo experiments and the CINNAMON-study

Abstract Background Heart failure is often accompanied by renal dysfunction, which indicates a pathophysiological connection between the heart and kidneys. Empagliflozin, a SGLT2 inhibitor, showed beneficial effects on both cardiovascular and renal endpoints. Mechanistically, however, it is unclear whether the empagliflozin-dependent renal protection is mediated via the inhibition of renal SGLT2 or rather indirectly via improved cardiac function. Interestingly, in the EMPEROR trials, there was a significant interaction of empagliflozin-dependent kidney protection with systolic contractile dysfunction. We hypothesized that Empagliflozin treatment ameliorates heart failure in response to chronic pressure overload in mice leading to improved renal function. We correlated these findings with data from our prospective, single-armed trial. Methods Transverse aortic constriction (TAC) or sham surgery was performed in C57BL/6J (wildtype, WT) and SGLT2 deficient mice (SGLT2-/-). Animals received either Empagliflozin (10 mg/kg bodyweight) or vehicle by daily oral gavage. Cardiac function was evaluated by echocardiography and kidney function by transdermal FITC-Sinistrin measurement (GFR), urinary albumin/creatinine ratio (UACR) and Siriusred fibrosis staining. Results After 10 weeks, echocardiography confirmed TAC induced pressure-overload, leading to reduced left ventricular ejection fraction (LVEF) and diastolic dysfunction. Empagliflozin attenuated changes in LVEF (Fig. A) and improved diastolic dysfunction (data not shown). Interestingly, at 10 weeks, TAC reduced GFR, increased UACR and tended to increase renal fibrosis, which was attenuated by empagliflozin (Fig. B, C and D). To test if direct inhibition of SGLT2 in the heart and kidney is mechanistically involved, TAC surgery was repeated in SGLT2-deficient mice (SGLT2-/-). In fact, exposure to TAC resulted in comparable reduction of LVEF in SGLT2-/- mice and Empagliflozin prevented this deterioration similar to WT mice (Fig. E vs. A). Surprisingly, Empagliflozin also prevented GFR deterioration 10 weeks after TAC in mice lacking SGLT2 (SGLT2-/-) with comparable magnitude as in WT mice (Fig. F), suggesting that the reno-protective effect of Empagliflozin was independent from renal SGLT2 inhibition. The effect of empagliflozin on the heart and kidney was also investigated in patients with HF (prospective, single-arm CINNAMON-study, DRKS00031101). After 180 days of Empagliflozin treatment (10 mg), there was a significant improvement in LVEF, NT-proBNP levels and KCCQ-12 Scores (Fig. G-I) and the effects on UACR and GFR are subject of investigation. Conclusion This is the first study investigating the role of SGLT2 in Empagliflozin-dependent kidney protection of mice that develop heart failure after TAC. Importantly, empagliflozin treatment prevented deterioration of LVEF and GFR independent of the presence of SGLT2 in mice and improved cardiac markers and quality of life in patients.

The Utility of Baseline Characteristics and [123I]MIBG Cardiac Adrenergic System Scintigraphy in Qualifying Patients with Post-Infarction Heart Failure for Implantable Cardioverter-Defibrillator (ICD) Placement.

Background: Post-infarction heart failure with reduced ejection fraction (HFrEF) patients often face persistent risks of sudden cardiac arrest leading to sudden cardiac death. While implanting a cardioverter-defibrillator (ICD) can enhance prognosis, complications and costs limit its widespread use. Current patient qualification criteria, relying on imperfect parameters, require refinement. The impairment of the cardiac adrenergic system in heart failure is associated with ventricular arrhythmias. The goal of the study was to assess the utility of cardiac adrenergic system scintigraphy in qualifying patients for ICD placement. Methods: In this prospective study of 85 post-infarction HFrEF patients at a single center, clinical assessments, laboratory tests, echocardiography, [123I]MIBG scintigraphy, and ICD implantation were performed. Scintigraphy involved planar chest images and evaluating the heart-to-mediastinum ratio (H/M) and washout rate (WO). SPECT imaging assessed [123I]MIBG uptake in 17 left ventricular segments to calculate the summed difference score (SDS). Results: During a median of 4-year follow-up, 22% of patients experienced appropriate ICD interventions, and 25% of patients died or underwent heart transplantation. The mean values of analyzed parameters did not significantly differ between groups. In the univariate analysis, younger age and moderately impaired left ventricular ejection fraction (LVEF) were correlated with more frequent ICD interventions. In comparison, older age and elevated NT-proBNP levels were associated with death or heart transplantation. Additionally, the univariate analysis identified SDS-15' as a prognostic factor for death/heart transplant. The multivariate analysis identified predictors for ICD interventions, including younger age, an EF of 30% or greater, and a larger left ventricular end-diastolic diameter. In contrast, older age and an LVEF of less than 25% were significant predictors of death or heart transplantation. Conclusions: Scintigraphic parameters did not effectively predict ICD interventions or death/heart transplantation, though the summed difference score demonstrated potential as a prognostic factor. Younger age with moderately impaired EF correlated with frequent ICD interventions, while in older age, EF < 25% predicted death or transplantation. Further investigation is needed for patients with borderline EF values.

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.

Early postoperative outcomes of modified del Nido cardioplegia in coronary artery bypass surgery in patients with low ejection fraction.

This study aimed to investigate the intraoperative and early postoperative effects of modified del Nido cardioplegia (DNC) compared to classic blood cardioplegia (BC) in patients with impaired left ventricular ejection fraction (EF) who underwent isolated coronary artery bypass grafting (CABG). A total of 123 patients (108 males, 15 females; mean age: 62.2±8.5 years; range, 42 to 78 years) with an EF of 35% or lower who underwent on-pump CABG were included in the retrospective study between December 2022 and December 2023. The patients were divided into two groups according to the type of cardioplegia used: Group 1 (n=74) was designated as the BC group, and Group 2 (n=49) was designated as the DNC group. The groups were compared in terms of aortic cross-clamp duration, cardiopulmonary bypass (CPB) duration, need for defibrillation during weaning from CPB, positive inotrope requirement, intra-aortic balloon pump requirement, postoperative troponin-I levels, postoperative atrial fibrillation occurence, postoperative prolonged ventilation, development of postoperative neurologic complications, need for reintervention due to postoperative bleeding, postoperative transfusion requirement, and EF values at one month after the operation. There was no significant difference between the two groups in the terms of aortic cross-clamp and CPB duration (p=0.955 vs. p=0.816). Additionally, there was no significant difference in the need for intra-aortic balloon pump usage between the two groups (p=0.105). Dopamine and dobutamine usage were significantly lower in Group 2 (p=0.04 and p=0.05, respectively). The intraoperative requirement for defibrillation was significantly lower in Group 2 (p=0.01). In addition, troponin levels at 12 h postoperatively were significantly lower in Group 2 (p=0.03). The incidence of postoperative atrial fibrillation was significantly lower in Group 2 (p=0.02). Moreover, there was no significant difference in EF values at one month after the operation (p=0.08). In patients who underwent CABG with reduced EF, modified DNC provided myocardial protection comparable to classic BC. Additionally, the need for intraoperative defibrillation and postoperative inotropic agents, as well as the incidence of postoperative atrial fibrillation, were lower in patients operated with DNC.

Eight-Year Outcomes of Patients With Reduced Left Ventricular Ejection Fraction Who Underwent Transcatheter Aortic Valve Replacement With a Self-Expanding Bioprosthesis

Conflicting results have been reported regarding the relationship between impaired left ventricular ejection fraction (LVEF) and adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) and long-term clinical data are lacking.The aims of this study were to investigate the long-term outcomes of patients with reduced LVEF undergoing TAVRData deriving from patients undergoing TAVR between 2007 and 2017 in 13 Italian centers were prospectively collected. Patients were stratified in those with normal LVEF and reduced LVEF. The latter was further classified according to ischemic or non-ischemic etiology. The primary endpoint was a composite of all-cause death and re-hospitalizations, the secondary endpoints were the isolated composers of the primary one and cardiac death. Overall, 2626 patients were included in the analysis, 68.1% with NLVEF and 31.9% with reduced LVEF. At eight years, reduced LVEF was significantly associated with the primary endpoint (adj. HR 1.17 95% CI 1.06-1.29). Consistent findings were evident for the composite endpoint. No differences in these trends were found at 30 days landmark analyses. Compared to non-ischemic etiology, ischemic reduced LVEF was associated with an increased risk of cardiac death (adj. HR 1.43 95% CI 1.02-2.02). In conclusion, patients with reduced LVEF undergoing TAVR are exposed to a progressively increased risk of death and re-hospitalizations even at very long-term follow-up.

Prognostic value of ventricular arrhythmia in early post-infarction left ventricular dysfunction: the French nationwide WICD-MI study.

Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e. within 3 months of hospital discharge) has not yet been specifically evaluated in post-myocardial infarction patients with impaired LVEF. Such was the aim of this retrospective study. Data analysis was based on a nationwide registry of 1032 consecutive patients with LVEF ≤ 35% after acute myocardial infarction who were implanted with an ICD after being prescribed a wearable cardioverter-defibrillator (WCD) for a period of 3 months upon discharge from hospital after the index infarction. ICDs were implanted either because a sustained VA occurred while on WCD (VA+/WCD, n = 72) or because LVEF remained ≤35% at the end of the early post-infarction phase (VA-/WCD, n = 960). The median follow-up was 30.9 months. Sustained VAs occurred within 1 year after ICD implantation in 22.2% and 3.5% of VA+/WCD and VA-/WCD patients, respectively (P < .0001). The adjusted multivariable analysis showed that sustained VAs while on WCD independently predicted recurrence of sustained VAs at 1 year (adjusted hazard ratio [HR] 6.91; 95% confidence interval [CI] 3.73-12.81; P < .0001) and at the end of follow-up (adjusted HR 3.86; 95% CI 2.37-6.30; P < .0001) as well as 1-year mortality (adjusted HR 2.86; 95% CI 1.28-6.39; P = .012). In patients with LVEF ≤ 35%, sustained VA during the early post-infarction phase is predictive of recurrent sustained VAs and 1-year mortality.

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.

Cardiogenic shock in phaeochromocytoma multisystem crisis- a case report

Abstract Background Phaeochromocytoma multisystem crisis (PMC) is characterised by labile blood pressures (extremes of hypo- and/or hypertension) and multiorgan failure as a result of catecholamine excess. Initial stabilisation requires pharmacological and/or mechanical circulatory support, followed by institution of antihypertensives to correct the underlying pathophysiology. Case summary A previously well 40-year-old male developed sudden onset of breathlessness. On presentation, he was in shock with multiorgan failure. He required intubation, mechanical ventilation, dual inotropic support and renal replacement therapy. Bedside echocardiogram showed a severely impaired left ventricular ejection fraction (LVEF) of 25%. Coronary angiography revealed normal coronary arteries. In view of raised inflammatory markers and transaminitis, a CT abdomen/pelvis was performed. An incidental left adrenal mass was found. Further work-ups revealed raised plasma metanephrine and normetanephrine, 24-hour urine epinephrine and norepinephrine. A cardiac magnetic resonance (CMR) showed myocardial inflammation and reverse Takotsubo pattern of regional wall motion abnormality (RWMA). The diagnosis of cardiogenic shock and stress cardiomyopathy secondary to phaeochromocytoma multisystem crisis was made. He was subsequently initiated on α- and β-blockers and goal-directed medical therapy for heart failure. A 68Ga-DOTATATE scan showed avid tracer uptake of the left phaeochromocytoma. An interval CMR 3 weeks from presentation showed near normalisation of the LVEF and RWMA. He underwent a successful laparoscopic left adrenalectomy and was antihypertensive-free since. Conclusion The clinical suspicion for PMC as the cause of cardiogenic shock requires astute clinical judgement, while the management requires understanding of the underlying pathophysiology that call for multidisciplinary inputs.

Temporal trajectory and left ventricular ejection fraction association of eight circulating biomarkers in first acute myocardial infarction patients: a 12-month prospective cohort study.

Our study aimed to explore the temporal trajectory of eight circulating biomarkers, measured serially over 12 months, in a prospective observational cohort of patients with acute myocardial infarction (AMI) and to investigate the association between these biomarkers and left ventricular ejection fraction (LVEF) during follow-up assessments. We enrolled 155 patients admitted for a first AMI requiring percutaneous coronary intervention (PCI). Baseline characteristics, laboratory test results, and cardiac ultrasound examinations were collected at pre-PCI (H0), immediately post-PCI (H24), at discharge (D3), and at 6 months (M6) and 12 months (M12) post-PCI. Blood samples were analysed for established and emerging biomarkers described in left ventricular dysfunction: soluble suppression of tumorigenicity 2 (sST2), interleukin-6 (IL-6), osteopontin, angiopoietin-2, insulin-like growth factor-binding protein 2 (IGFBP-2), growth differentiation factor 15 (GDF-15), hepcidin, and galectin-3. Values at H24, D3, M6, and M12 were compared with value at H0. Three kinetic profiles were identified, with six biomarkers peaking during the acute MI phase. Crude relationships between clinical variables and the peak values (highest observed between H0 and D3) of each biomarker were studied. Peak levels of sST2, IL-6, osteopontin, and angiopoietin-2 demonstrated significant correlations with both baseline and follow-up LVEF values. The assessment of the temporal trajectories of these biomarkers and their associations with LVEF suggests that sST2, IL-6, osteopontin, and angiopoietin-2 hold significant promise as companion biomarkers. These biomarkers may improve the identification of patients at risk for developing impaired LVEF following AMI, thereby enabling more targeted and effective management strategies.