Impaired Left Ventricular 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.

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 < 0.005), primarily driven by increased mortality (23% vs. 9.6%; p < 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p < 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 < 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 < 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p < 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.

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 <50% and three patients (10%) had an impaired right ventricular ejection fraction of <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.

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.

Decision-making regarding subcutaneous implantable cardioverter defibrillator as primary prevention in patients with low ejection fraction.

Conventional transvenous implantable cardioverter-defibrillator (TV-ICD) is the standard device used for primary prevention of sudden cardiac death (SCD) in patients with reduced left ventricular ejection fraction (LVEF). Nonetheless its use is associated with lead-related complications including infection and malfunction. A subcutaneous implantable cardioverter-defibrillator (S-ICD) offers an alternative option without the need for a transvenous lead but has limitations. The decision to implant a TV-ICD or S-ICD in patients with impaired LVEF for primary prevention of SCD is controversial. Several randomised controlled trials and large observational studies have confirmed similar safety and efficacy of S-ICDs and TV-ICDs in such population. A literature review was conducted to compare the outcomes of subcutaneous (S-ICD) versus transvenous (TV-ICD) implantable cardioverter-defibrillators. Databases including PubMed, MEDLINE, and Cochrane were searched for relevant peer-reviewed articles. Studies were selected based on relevance and quality. Key outcomes like complication rates, efficacy, and patient survival were summarized in a comparative table. Different factors that influence the choice between an TV-ICD and S-ICD for primary prevention of SCD in patients with LVEF are highlighted to guide selection of the appropriate device in different patient populations. Moreover, future perspective on the combination of SICD with leadless pacemaker, and the latest development of the extravascular implantable cardioverter defibrillator are also discussed. S-ICD offers a safe and efficacious option to primary prevention in reduced ejection fraction. Future development including incorporation of leadless pacemaker will add to the arsenal of choice to protect patients from sudden cardiac death.

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

Prognostic Impact of Left Ventricular Ejection Fraction Improvement after Transcatheter Aortic Valve Replacement.

Introduction: Transcatheter aortic valve replacement (TAVR) has become an efficient and safe alternative to surgical aortic valve replacement (SAVR). While severe aortic stenosis as well as severe aortic regurgitation (AR) are known to negatively impact left ventricular ejection fraction (LVEF), prior studies have shown that TAVR can lead to an improvement in LVEF. Thus far, little is known about the prognostic implication of LVEF improvement as a sole predictor of outcomes. Therefore, the aim of this study was to assess the prognostic impact of LVEF impairment before TAVR, as well as early LVEF improvement in patients undergoing TAVR. Materials and Methods: Patients undergoing TAVR in a large tertiary university hospital were consecutively included in a prospective registry. Transthoracic echocardiography (TTE) was performed at baseline, after 1 month and annually thereafter. Significant LVEF improvement was defined as a relative increase of ≥10% in LVEF at 30 days compared to baseline LVEF. The primary outcome was all-cause mortality at 1 year. Secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, non-fatal myocardial infarction, stroke, bleeding and unplanned re-interventions of the aortic valve at 5 years. Results: Among 1655 patients who underwent TAVR between September 2011 and April 2024, the LVEF at baseline was available for 1556 patients. Of these, 1031 patients (66.2%) had preserved LVEF at baseline (LVEF ≥ 53%), whereas 303 patients (19.5%) had moderately reduced LVEF (40-52%) and 222 patients (14.3%) had severely reduced LVEF (<40%). Out of the patients with impaired LVEF, 155 (40.4%) patients showed a significant improvement in LVEF ≥10% after 30 days, while 229 (60.6%) patients showed no significant LVEF improvement (<10%). Patients with preserved LVEF at baseline had significantly better mortality outcomes than those with severely reduced LVEF (p < 0.001). LVEF improvement was associated with a survival benefit after 1 year (p = 0.009, HR 2.68, 0.95 CI 1.23-5.85) which diminished after 5 years (p = 0.058), but patients with LVEF improvement showed lower MACE rates at 5 years (p < 0.001). Conclusions: Preserved LVEF before TAVR is an independent predictor for improved outcomes. Additionally, early improvement in LVEF is associated with beneficial outcomes in patients undergoing TAVR.

Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation

BackgroundA novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. ObjectivesThis study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. MethodsThis multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). ResultsA total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). ConclusionsDirect TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

DNMT3A-mutant clonal haematopoiesis and the recovery of patients with acute ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart foundation Background Haematopoietic stem cells can acquire mutations and produce mutant blood cells. When this occurs in the absence of overt blood disease, it is clonal haematopoiesis of indeterminate potential (CHIP). CHIP is a novel, independent risk factor for ischaemic heart disease and heart failure (HF)(1). However, the molecular mechanisms are poorly understood. Myocardial infarction (MI) is a leading cause of HF due to ventricular remodelling and scar formation(2). We postulate CHIP mutations result in aberrant inflammation that contributes to maladaptive ventricular remodelling following MI. We investigated clinical outcomes and immune cell biology in CHIP and non-CHIP patients (pts) with acute ST-segment elevation MI (STEMI). Purpose Identify and quantify mutations with variant allele frequency (VAF)≥1% in STEMI pts. Assess leukocyte mutational burden. Investigate transcription profiles and leukocyte function in CHIP and non-CHIP STEMI pts. Methods 119 pts diagnosed with STEMI were prospectively recruited (REC19/SC/0362). We collected clinical data, including echocardiogram (echo) parameters and isolated plasma and peripheral blood mononucleated cells (PBMCs) from blood collected 48-96 hours post onset of chest pain. PBMCs were screened for mutations and analysed by flow cytometry. We assessed CHIP VAF with digital droplet PCR in flow-sorted monocytes (Mono), T and B-cells. We performed single-cell RNAseq (10x Genomics) on PBMCs. Luminex or ELISA kits were used to measure plasma proteins. Results 59/119 recruited pts had CHIP (VAF≥1%). CHIP pts were significantly older than non-CHIP pts. DNMT3A was the most commonly mutated gene (28%), followed by TET2 (17%) and ASXL1 (5.3%). 53 pts had impaired LV ejection fraction (LVEF) at admission and a follow-up Echo at median 4.6 months (2.5-8 IQR) post STEMI. They were classified as responder (R) n=24, Δ LVEF≥5% or non-responder (NR) n=29, ΔLVEF&amp;lt;5%. Pts with DNMT3A CHIP were 12 times more likely to be NR (p=0.02). Baseline LVEF was similar in CHIP and non-CHIP pts, but ΔLVEF was significantly reduced in DNMT3A vs non-CHIP pts (p&amp;lt;0.01). DNMT3A mutations were highest in Mono (mean VAF 6.3%), present in B cells (3%) but rare in T cells (1.7%). Within the Mono population, DNMT3A mutant pts had significantly higher proportions of classical Mono compared to non-CHIP (p=0.02). Using scRNAseq, we computed Mono trajectories and differential gene expression. Compared to non-CHIP, DNMT3A-mutant samples upregulated receptor for advanced glycation end-products (RAGE) and toll-like receptor signaling gene signatures. Despite this, we did not observe raised leukocyte count or detect increased levels of inflammatory cytokines in DNMT3A-mutant pts plasma samples. Conclusions DNMT3A CHIP is associated with poor LVEF recovery post-STEMI due to a dysregulated inflammatory response to acute myocardial injury. Furthermore, our data suggests that this may occur via different mechanisms than non-CHIP NR.

Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.

Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO. Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM). A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM. Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.