Nonischemic Etiology Research Articles

Long-term outcomes among out-of-hospital cardiac arrest survivors with reversible vs. non-reversible causes.

A reversible cause of out-of-hospital cardiac arrest (OHCA) is vaguely defined in international guidelines as an identifiable transient or potentially correctable condition. However, studies evaluating long-term outcomes of patients experiencing OHCA due to reversible and non-reversible causes are lacking. We aimed to determine differences in long-term outcomes in OHCA survivors according to different aetiology. From the British Columbia Cardiac Arrest registry, adults with non-traumatic OHCA (2009-2016) surviving to hospital discharge were identified. Patients were categorized by OHCA aetiology combining reversibility and underlying ischaemic aetiology. The primary outcome was a composite of all-cause mortality, recurrent OHCA, or re-hospitalization for sudden cardiac arrest or ventricular arrhythmias. Using the Kaplan-Meier method and multivariable Cox regression models, we compared the risk of the composite outcome according to different OHCA aetiology. Of 1325 OHCA hospital-discharge survivors (median age 62.8 years, 77.9% male), 431 (32.5%) had reversible ischaemic, 415 (31.3%), non-reversible ischaemic, 99 (7.5%), reversible non-ischaemic, and 380 (28.7%), non-reversible non-ischaemic aetiologies. At 3 years post discharge, the Kaplan-Meier event-free rate was highest in patients with a reversible ischaemic aetiology [91%, 95% confidence interval (CI) 87-94%], and lowest in those with a reversible non-ischaemic aetiology (62%, 95% CI 51-72%). In multivariate analyses, compared with non-reversible non-ischaemic cause, reversible ischaemic cause was associated with a significantly lower hazard ratio (HR; 0.52, 95% CI 0.33-0.81), reversible non-ischaemic cause with a significantly higher HR (1.53, 95% CI 1.03-2.32), and non-reversible ischaemic cause with a non-significant HR (0.92, 95% CI 0.64-1.33) for the composite outcome. Compared to other aetiologies, the presence of a reversible ischaemic cause is associated with improved long-term OHCA outcomes.

Proteomics-based computational modelling of myocardial metabolism for personalized phenotyping and outcome prediction in advanced heart failure

Abstract Background Perturbations of myocardial metabolism and energy depletion are well-established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans [1]. Computational modelling of the heart of individual patients represents an emerging precision medicine approach for personalized diagnosis of specific disease mechanisms and tailored clinical decision-making [2,3]. Purpose To determine the ability of computational modelling of patient-specific myocardial metabolism to assess individual bioenergetic phenotypes and their prognostic implications in HF. Methods Based on proteomics-derived enzyme intensity profiles in cardiac biopsies, we recently developed a computational model of myocardial metabolism capturing all pathways along energy-delivering substrates are processed to generate ATP [4]. Using this framework, we studied the individual energetic state in 17 sex-matched nonfailing controls and 48 patients with advanced HF (LVEF 20±10%, 72.9% non-ischemic aetiology, 52.1% females, 29.8% diabetics) undergoing heart transplantation (n=25) or ventricular assist device (VAD) implantation (n=23). The bioenergetic impact of alterations in substrate availability and myocardial workload were simulated, and the model’s ability to predict myocardial reverse remodelling after VAD implantation was assessed. Results Compared to controls, HF patients had a reduced ATP production capacity (p<0.01), although there was considerable interindividual variance, ranging from severely decreased to normal values. While overall oxygen consumption was lower in failing hearts, the amount of ATP generated per mole of oxygen did not differ (p=0.16). Maximum uptake capacity of fatty acids, glucose, and amino acids was comparable. By contrast, maximum uptake capacity of ketone bodies and lactate was reduced in the failing heart (p for both <0.05). There was a shift from fatty acid to glucose utilization in most HF patients, depending on substrate availability and myocardial workload. The ratio of fatty acid to glucose oxidation distinguished patients with LVEF recovery >10% after VAD implantation (C-index 0.93, p<0.01; Picture 1B) and correlated significantly with improvement in post-operative LVEF (r=0.67, p<0.01). ATP production capacity was not associated with reverse remodelling after VAD implantation. Conclusions Computational modelling identified a subset of advanced HF patients with preserved myocardial metabolism despite a similar degree of systolic dysfunction. Myocardial substrate preference but not ATP production capacity was associated with myocardial recovery after VAD implantation, which suggests a potential for substrate manipulation as a therapeutic approach in those with deranged fuel use. Computational assessment of myocardial metabolism in HF may improve understanding of disease heterogeneity, individual risk stratification, and guidance of personalized clinical decision-making in the future.

CMR characterisation of patients with heart failure and left bundle branch block

Abstract Introduction Cardiac magnetic resonance (CMR) is recommended internationally for tissue characterisation, volumetric assessment and assessment of prior myocardial infarction (1). Patients with left bundle branch block (LBBB) form a significant sub-group of individuals, however, there is limited data available to accurate determine whether LBBB is associated with any CMR-definable phenotypes. Aim We aimed to identify the distinctive cardiac magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. Methods Participants from the MATCH (MyocArdial Tissue CHaracteristics in patients with heart failure according to glycaemic status) registry were prospectively enrolled. Exclusion criteria included: LVEF >40% at initial evaluation, established diagnosis of coronary artery disease, known presence of structural heart disease, suspected myocarditis, congenital heart disease and significantly impaired renal function. Following identification of HF, guideline-directed medical therapy was initiated based on the decision of the treating physician. LV recovery was defined as achieving ≥10% absolute improvement to a level of 40% or greater of LVEF from baseline evaluation upon the date of CMR quantification. Electrocardiograms were analysed to establish the presence or absence of LBBB. Results A total of 391 patients were recruited including 115 (29.4%) presenting with LBBB. Compared to controls, LBBB patients exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8±12 vs. 38± 12 %, p=0.105) or right ventricular ejection fraction (RVEF). The prevalence of ischaemic scar (18.3% vs 21%, p=0.54), non-ischaemic fibrosis (25.2% vs 32.6%, p=0.15) and inducible ischaemia (6.1% vs. 7.6%, p=0.6) was comparable in patients with LBBB and those without. The overall rate of LV recovery was not significantly different between LBBB and non-LBBB patients (27.8% vs. 33%, p=0.32) from their baseline evaluation to the time of CMR assessment (70 [42 - 128] days). In the multivariate logistic regression, reduced LVEF remained an independent predictor of LV non-recovery in patients with LBBB, even after adjusting for gender and QRS duration (OR 0.93, 95%CI 0.87 – 0.99, p=0.03). In contrast, this association was not observed among patients without LBBB, whereas ischaemic scar was the primary predictor of LV non-recovery (OR 4.31, 95%CI 1.85 – 10.04, p=0.0007). Conclusion In this study patients presenting with a combination of HFrEF and LBBB had a larger LV cavity and smaller RV cavity than those without LBBB. However, there were no differences in the prevalence of ischaemic scar, non-ischaemic scar of inducible ischaemia according to the presence of absence of LBBB. Rates of LV recovery were similar between LBBB and non-LBBB patients.Clinical CMR ParametersSegmental Distributions

Long-Term Outcomes in ICD: All-Causes Mortality and First Appropriate Intervention in Ischemic and Nonischemic Etiologies

Real-life data comparing the long-term outcome in patients with different heart diseases carrying an implantable cardioverter defibrillator (ICD) are scarce. This study aimed to compare the long-term risk of the first appropriate ICD intervention and overall survival in patients with ICD and heart disease of different etiologies. Patients with an ICD implanted between January 1, 2010, and December 31, 2022, followed in our center were included. Study outcomes were all-cause mortality and first appropriate ICD intervention. A comparison between ischemic heart disease (IHD) and non-IHD (NIHD) was performed. In NIHD different etiologies of dilated cardiomyopathy (DCM) were analyzed. Overall, 1184 patients (592 IDH; 592 NIHD) were included. During a median follow-up of 53 months all-cause death occurred in 399 patients (34%) whereas first appropriate ICD intervention occurred in 320 (27%). All-cause mortality was significantly higher in IHD vs NIHD patients (60% vs 43%; p <0.0001) but no differences in appropriate ICD intervention rate at 10 years (34% vs 40%; p = 0.125) were observed. In patients with NIHD, a higher 10-year mortality rate was found in valvular heart disease, post-radio/chemotherapy DCM (rctDCM), and hypertensive DCM. Hypertrophic cardiomyopathy, alcoholic DCM, and rctDCM were the least arrhythmic phenotypes in NIHD. Of note, inappropriate interventions in alcoholic DCM and rctDCM were higher than appropriate ones. In conclusion, the rate of ICD-appropriate interventions and mortality is different according to the etiology of heart disease and cardiovascular risk profile; this should be taken into consideration in the prognostic stratification of these patients at the time of implantation.

Beneficial effects of extravascular lung water index-guided volum management in patients with cardiogenic shock

Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95%CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value (AUC=0.54, 95%CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

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.

Cardiogenic shock in general intensive care unit: a nationwide prospective analysis of epidemiology and outcome

Abstract Aims Cardiogenic shock (CS) is a life-threatening disease burdened by a mortality up to 50%. The epidemiology has changed with non-ischaemic aetiologies being predominant, although data were mainly derived from patients admitted to dedicated acute cardiac care. We report the epidemiology and outcome of patients with CS admitted to general intensive care unit (ICU). Methods and results Prospective multicentric epidemiological study including 314 general ICU adhering to the GiViTI nationwide registry from 2011 to 2018, excluding cardiac arrest. The primary endpoint of the study was mortality. The association between clinical factors and mortality was evaluated using a logistic regression model. The odds ratios (ORs) of the covariates quantify their association with mortality during hospitalization. A total of 11 052 patients admitted to general ICU {incidence 2.17%; median age 72 [interquartile range (66–81)], 38.7% were women} with CS were included. Forty-seven per cent of patients had more than three organ insufficiency at the time of admission. The most common CS aetiologies were left heart failure (LHF, 5247—47.5%); acute myocardial infarction (3612—32.6%); right heart failure (RHF, 515—4.6%); and biventricular failure (532—4.8%). A total of 85.5% were mechanically ventilated during the ICU hospitalization. The overall ICU mortality was 44.8%, increasing to 53.4% during the hospitalization in the index hospital and to 54.3% at the latest hospital. Right heart failure–cardiogenic shock patients exhibited the highest mortality risk [OR: 1.19, 95% confidence interval (CI) (0.94–1.50); P &amp;lt; 0.001], followed by biventricular CS [OR 1.04, 95% CI (0.82–1.32)]. Respiratory failure [OR 1.13 (95% CI 1.08–1.19)], coagulation disorder [1.17 (95% CI 1.1–1.24)], renal dysfunction [OR 1.55 (95% CI 1.50–1.61)], and neurological alteration [OR 1.45 (95% CI 1.39–1.50)] were associated with worsen outcome along with severe hypotension [systolic blood pressure &amp;lt; 70 mmHg—OR 2.35, 95% CI (2.06–2.67)], increasing age [OR 2.21 95% CI (2.01–2.42)], and longer ICU stay prior to admission (two-fold increase for each 4.7 days). Conclusion In the general ICU, the aetiology of CS, excluding cardiac arrest, remains characterized mostly by LHF with RHF–CS burdened by higher mortality. Multiorgan failure at admission and longer hospital stay before ICU admission predispose to worsen outcome.

Short term outcomes and resource utilization in de-novo versus acute on chronic heart failure related cardiogenic shock: a nationwide analysis.

There has been growing recognition of non-ischemic etiologies of cardiogenic shock (CS). To further understand this population, we aimed to investigate differences in clinical course between acute on chronic heart failure related (CHF-CS) and de-novo CS (DN-CS). Using the Nationwide Readmission Database, we examined 92,426 CS cases. Outcomes of interest included in-hospital and 30-day outcomes and use of advanced heart failure therapies. Patients with DN-CS had higher in-hospital mortality than the CHF-CS cohort (32.6% vs. 30.4%, p < 0.001). Mechanical circulatory support (11.9% vs. 8.6%, p < 0.001) was more utilized in DN-CS. Renal replacement therapy (13.8% vs. 15.5%, p < 0.001) and right heart catheterization (16.0% vs. 21.0%, p < 0.001) were implemented more in the CHF-CS cohort. The CHF-CS cohort was also more likely to undergo LVAD implantation (0.4% vs. 3.6%, p < 0.001) and heart transplantation (0.5% vs. 2.0%, p < 0.001). Over the study period, advanced heart failure therapy utilization increased, but the proportion of patients receiving these interventions remained unchanged. Thirty days after index hospitalization, the CHF-CS cohort had more readmissions for heart failure (1.1% vs. 2.4%, p < 0.001) and all causes (14.1% vs. 21.1%, p < 0.001) with higher readmission mortality (1.1% vs. 2.3%, p < 0.001). Our findings align with existing research, demonstrating higher in-hospital mortality in the DN-CS subgroup. After the index hospitalization, however, the CHF-CS cohort performed worse with higher all-cause readmission rate and readmission mortality. The study also underscores the need for further investigation into the underutilization of certain interventions and the observed trends in the management of these CS subgroups.

Prognostic indicators of vector electrocardiography in patients with chronic heart failure with reduced left ventricular ejection fraction

Relevance. Computed vector electrocardiography (VECG) is a method of visualization of the total electrical vector of the heart in 3‑dimensional space based on 12 leads and a known computational procedure. VECG may be an additional method to assess the severity and prognosis of patients with chronic heart failure (CHF).Objective. To determine VECG parameters associated with unfavorable prognosis in patients with CHF with reduced ejection fraction (CHFpEF).Materials and methods. VECGs of 100 patients with CHFpEF were analyzed. All patients underwent baseline clinical examination, echocardiography and natriuretic peptide (NT-proBNP) determination. Patients with both ischemic (55 patients, of whom 10 died) and non-ischemic (45 patients, of whom 6 died) etiologies were included. During follow-up for 24 months, fatal outcomes were recorded. The correlation of ECG and NT-proBNP parameters with patients’ prognosis was evaluated.Results. A total of 16 patients died in the study. According to VECG data the surviving patients had lower spatial QRS-T angle in comparison with the deceased ones (p=0,025). There was a trend towards lower planarity index in the group of deceased patients (p=0.09). ROC-analysis was carried out, according to the results of which with sensitivity 76,5% and specificity 62,7% the cut-off value of 156º of QRS-T spatial angle was obtained, exceeding which the probability of lethal outcome will increase (p=0,002). There was a correlation between lethal outcome in patients with a QRS-T angle value greater than 156º and NT-proBNP level (p=0.017). The threshold value of unfavorable prognosis for NT-proBNP was 927.1 pg/ml.Conclusion. The VECG method is available and promising in the diagnosis and monitoring of patients with CHFpEF. The most informative parameters of ECG for detection of suspicion of CHFpEF are spatial QRS-T angle and planarity index. The results obtained in this study allow us to speak about the prognostic value of the QRS-T angle for patients with CHFpEF.

Abstract Tu052: RPN6-Serine14 Phosphorylation by PKA Protects Against Systolic Overload-Induced Cardiac Remodeling and Heart Failure

The ubiquitin-proteasome system is the main proteolytic pathway for quality control (PQC) and regulatory degradation of proteins in living cells. Systolic overload, as seen in hypertension and aortic stenosis, is a leading cause of heart failure (HF). Proteasome functional insufficiency is implicated in HF caused by systolic overload. Previous studies have established that Ser14-RPN6 phosphorylation (pS14-RPN6) mediates the activation of 26S proteasomes by protein kinase A. However, the pathophysiological significance of pS14-RPN6 in systolic overload remains to be established. We hypothesize that pS14-RPN6 helps maintain proteostasis and protects the heart during systolic overload. We observed a significant increase in myocardial pS14-RPN6 and ubiquitin conjugates in human HF of ischemic or non-ischemic etiologies (p=0.020, p=0.034) and similarly in wild type (WT) mice after 2 weeks of transverse aortic constriction (TAC) (p&lt;0.0001, p=0.001). To investigate the role of pS14-RPN6 in vivo, our lab created Rpn6 S14A (S14A) knock-in mice where Ser14-Rpn6 phosphorylation is blocked. Here we have compared the responses to TAC between WT and S14A mice. We found that TAC-induced increases in myocardial proteasome peptidase activities were significantly attenuated, and accumulation of ubiquitin conjugates exacerbated in S14A mice (p&lt;0.0001; p&lt;0.0005). Serial echocardiography revealed that S14A mice displayed significantly greater left ventricular (LV) end-diastolic posterior wall thickness and LV mass to body weight ratios at 1- and 12-week post-TAC (p=0.024, 0.0003; p=0.005, 0.01), and lower ejection fraction at 12-week post-TAC than WT mice (p=0.035). S14A mice also showed greater heart weight to tibial length (TL) and ventricular weight to TL ratios at 1 and 12-week post-TAC (1-week, p=0.043, 0.039; 12-week, p=0.007, 0.006). Wheat germ agglutinin and picrosirius red staining indicated a greater cardiomyocyte cross-sectional area and cardiac fibrosis in 12-week post-TAC S14A mice vs. WT mice (p&lt;0.0001; p=0.005). These novel findings demonstrate compellingly that myocardial pS14-RPN6 helps maintain proteostasis, curtails cardiac hypertrophy and delays heart failure occurrence during systolic overload

The influence of sex on heart failure mortality.

Little research has investigated how sex may affect the prognosis of patients with chronic heart failure (HF). The present study was aimed at exploring sex-specific differences in prognosis in a cohort of patients with chronic HF, categorized according to severity of left ventricular dysfunction (HFrEF, HFmrEF and HFpEF), right ventricular (RV) dysfunction and ischemic (IHD) or nonischemic (no-IHD) etiology. This retrospective analysis included 1640 HF patients of whom 24% were females, 759 patients had IHD, 1110 patients had HFrEF, 147 patients had HFmrEF and 383 patients had HFpEF. The median follow-up period was 63 months (25th-75th 27-93). In the no-IHD group, no statistically significant sex differences emerged regarding survival, regardless of age and severity of cardiac dysfunction. In contrast, in the IHD group, females had a significantly lower event rate than males in the age group between 65 and 79 years [hazard ratio (HR) 0.39; 95% confidence interval (CI): 0.86-0.18; P < 0.01]; in addition, a lower event rate was observed in females compared with males among patients with HFrEF (HR 0.47; 95% CI: 0.88-0.25; P < 0.01), among patients without RV dysfunction (HR 0.58; 95% CI: 1.02-0.33; P = 0.048) and among patients without diabetes (HR 0.44; 95% CI: 0.84-0.23; P < 0.01). In nonischemic patients there was no difference between males and females in terms of survival whereas in patients with ischemic etiology survival was better in females among elderly patients, in HFrEF patients, in the absence of RV dysfunction and in the absence of diabetes.

Cardiac sympathetic activity and lethal arrhythmic events: insight into bell-shaped relationship between 123I-meta-iodobenzylguanidine activity and event rates

Background123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts.ResultsWe calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I.ConclusionsThe relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

Heart Failure With Improved Ejection Fraction: Prevalence, Predictors, and Guideline-Directed Medical Therapy.

Recently, a new category of heart failure with improved ejection fraction (HFimpEF) has emerged in the classification system. This is defined as the subgroup of patients with heart failure with reduced ejection fraction (HFrEF) whose left ventricular ejection fraction has recovered partially or completely, with no specific cut-off values established yet in the guidelines. In our review, we aim to provide an overview of prevalence, predictors, mechanism of remodeling, and management strategies regarding HFimpEF. These patients constitute a sizeable cohort among patients with reduced ejection fraction. Certain patient characteristics including younger age and female gender, absence of comorbid conditions, low levels of biomarkers, and non-ischemic etiology were identified as positive predictors. The heart undergoes significant maladaptive changes post failure leading to adverse remodeling influenced etiology and duration. Goal-directed medical therapy including beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs) have notably improved cardiac function by inducing reverse remodeling. Despite a more favorable prognosis compared to HFrEF, patients with improved ejection fraction (EF) still face clinical events and reduced quality of life, and remain at risk of adverse outcomes. Although the evidence is scarce, it is advisable to continue treatment modalities despite improvement in EF, including device therapies, to prevent relapse and clinical deterioration. It is imperative to conduct further research to understand the mechanism leading to EF amelioration and establish guidelines to identify and direct management strategies.

The effectiveness of cardiac contractility modulation: results of two-year follow-up

Aim. To evaluate the survival and dynamics of clinical and instrumental data in patients with chronic heart failure (CHF), atrial fibrillation (AF) and cardiac contractility modulation (CCM).Methods. There were included 54 patients (40 men, median age 59.7 [56.6; 63.9] years) with signs of CHF II (n=27, 50%) functional class and III (n=27, 50%) NYHA functional class, significantly decreased left ventricular ejection fraction (LVEF=30 [24,7; 35,5]%), LV dilatation and paroxysmal (n=27, 50%) or permanent (n=27, 50%) AF. In all patients, devices for CCM were implanted. The dynamics of clinical and instrumental parameters were assessed in 2, 6, 12 and 24 months after implantation. The actual survival patients with CCM was compared with the predicted survival calculated using the Seattle model of heart failure and MAGGIC risk score.Results. In 14 (28%) of patients CCM resulted in significantly increased clinical, echocardiographic parameters (increase in LVEF by 15 [11; 20]%, decrease in end-systolic volume by 68,5[37.5;104.5] ml and end-diastolic volume by 44 [30,100] мл), increase in walking distance during 6-minute walking test and decrease of NT-proBNP. The only factor significant for maximal response was non-ischemic etiology of CHF (χ2=4.54, p=0.034). During 2 years 21 (42%) patients died. The all-cause mortality in patients with CCM to the first year of observation was 16%, two-year all-cause mortality - 40%. These figures turned out to be significantly higher than predicted according to the Seattle model (χ2=10.93, p=0.001). The predicted and actual risk of death at 12-month follow-up turned out to be comparable when assessing survival parameters according to the MAGGIC scale. (χ2=2.24, p=0.134).Conclusion. CCM therapy in some patients with CHF of non-ischemic etiology can lead to an improvement of all clinical and instrumental characteristics. At the same time, there is no effect of CCM on the prognosis of patients with CHF. This fact may suggest the need of additional studies with increased number of cases.

Electrocardiographic predictors of haemodynamic benefit from biventricular pacing: the role of atrioventricular timing measures

Abstract Background Patients with heart failure (HF) and left bundle branch block (LBBB) are selected for biventricular pacing (BVP) cardiac resynchronisation therapy (CRT) based on their 12-lead ECG QRS complex duration (QRSd). This is due to the long-held belief that BVP delivers its beneficial effects almost exclusively by reducing ventricular dyssynchrony. Recent work (1) suggests that atrioventricular delay (AVD) shortening is another key mechanism of benefit and, therefore, that atrioventricular timing may be an important CRT substrate. The ideal 12-lead ECG measure to facilitate patient selection that yields benefits from this mechanism is yet to be elucidated. Purpose We set out to establish whether incorporating a measure of AV delay provides additional benefit over and above using QRSd when using the 12-lead ECG to select patients who are likely to obtain haemodynamic benefit from BVP. Methods We identified patients in sinus rhythm with HF and LBBB meeting clinical criteria for CRT who had undergone implantation of a BVP device and had also undergone high-precision haemodynamic assessment of BVP. This is where pacing is alternated between atrium-only pacing (AAI) and DDD pacing using BVP multiple times for each of a full range of AVDs during continuous beat-by-beat blood pressure recording to determine the peak haemodynamic benefit of BVP in each patient. We extracted potentially predictive, pre-specified intrinsic (unpaced) ECG features that incorporated left or right AV timing to varying extents: PR interval (PR), end-of-p-wave-to-R-wave-peak-time-V6 (Pend-RWPTV6), start-of-p-wave-to-end-of-QRS (P-QRSend) as well as conventional QRSd. Pearson's test assessed the unadjusted correlation between intrinsic ECG intervals and BVP haemodynamic benefit(∆SBP). A multiparametric regression analysis model was constructed to account for confounders and interactions between different ECG features. Results 53 eligible patients were identified. 39 were male (73.6%), 31 had non-ischaemic aetiology (58.5%), mean LVEF was 27.6% ± SD 4.79 and mean LVEDD was 57.9± SD 9.4mm. Unadjusted correlations between intrinsic ECG features were not strong but favoured P-QRSend as a potentially predictive feature; R2 values: PR 0.28 (p=0.04), Pend-RWPTV6 0.19 (p=0.18), P-QRSend 0.27 (p=0.054), QRSd 0.045 (p=0.75). However, the multiparametric model revealed that utilising both PR interval and Pend-RWPTV6 in a predictive model showed better-adjusted correlation with BVP haemodynamic benefit (R2 0.54, p=0.04). Conclusion ECG features that incorporate either right (PR interval) or left (Pend-RWPTV6) AVD or both (P-QRSend) are superior to QRSd for predicting haemodynamic benefit from BVP in patients with HF and LBBB. This further reinforces the role of AVD shortening as a mechanism of benefit of BVP and suggests that selecting patients on the basis of AV timing may yield more overall benefit from CRT delivered by BVP or potentially conduction system pacing.ECG interval measurementCorrelation Graphs

Identification of reentry vulnerable targets during substrate mapping for ablation in scar related VT: the "visual" reentry vulnerability index

Abstract Introduction Conduction abnormalities including zones of deceleration (DZ) &amp; late activation are functionally important targets for ablation in scar-related ventricular tachycardias (VT). Repolarisation heterogeneities are equally important but are not routinely assessed. Visualisation of a combination of both conduction &amp; repolarisation metrics whilst in sinus in the form of a re-entry vulnerability index (RVI) may enable more precise identification of critical ablation targets. Rationale: To test accuracy of a novel functional substrate mapping strategy combining conduction &amp; repolarisation metrics to "visually" estimate reentry vulnerability sites (RVIv) during scar related VT ablation without the need for offline processing required for "computational" RVI. Methods VT cases using a multipolar grid-catheter for contact mapping were reviewed. DZ &amp;areas of late activation were tagged on omnipolar LAT substrate maps. The corresponding unipolar repolarisation maps depicting local repolarisation time (LRT) based on the Wyatt method (WOI over T-Wave annotating to +dV/dt, UEGM-Filter 0.05-100Hz) were then displayed side-by-side with the LAT map. Timing reference was set to onset of surface QRS. Colour scale of LRT maps was set to start at or ahead of the timing of latest LAT. "Visual RVI" zones were identified if the tagged zone of late activation was overlapping and/or directly adjacent to an area of "early" repolarisation (defined as before or within 100ms of latest LAT point) based on colour. In visually identified RVI areas, temporal (timing difference in ms) &amp; spatial relationship (distance in mm) of EGMs with earliest RT (RTe) to EGM with latest AT (ATL) separated by max. 20mm were measured &amp; RVI calculated (RTe subtracted by ATL). Number of RVIv zones per map, RVI metrics &amp; distance from closest RVI to VT Exit site (defined per activation±entrainment or pace mapping) were assessed. The lower/negative the numeric RVI, the higher the vulnerability for reentry. Results 20 patients with scar-related reentry VT were included (90% male, 63.8±11.6 years, LVEF 36±16%, 60% ischemic/40% non-ischemic). LAT &amp; LRT map point counts were 4835±2625 and 3596±2805. In 17 (85%) patients at least 1 RVIv zone was identified, with on avg. 3.3±1.7 RVIv zones/patient. Manual RVIs were calculated to 10.4±78.9ms ( "most vulnerable" RVI was -227ms) with on avg. 9.5±5.3mm distance between RTe &amp; ATL. All maps with no RVIv zone on the mapped surface were of non-ischemic etiology. The shortest distance of RVIs to functionally critical sites during VT was 8.9±7.4mm (range 0-33mm). Conclusion Visual reentry vulnerability estimation based on a combination of established conduction and novel repolarisation maps is feasible &amp; may help to identify functionally critical zones during substrate mapping. Future efforts should include dedicated automated repolarisation mapping tools to facilitate integration of repolarisation dynamics in functional VT substrate mapping workflows.Figure 1Example Visual RVI Mapping

Left bundle branch area pacing optimized cardiac resynchronization therapy (LOT CRT) -comparative results to a CRT implanted patient population

Abstract Background Cardiac resynchronization therapy (CRT) is gold standard treatment option among patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF) and intraventricular conduction delay of left bundle branch block (LBBB) morphology. Purpose Left bundle branch area pacing optimized cardiac resynchronization therapy (LOT CRT) is a novel and promising approach for CRT candidate patients even in advanced intraventricular conduction delay, however convincing follow-up data regarding this patient group is still lacking. Methods In our observational registry 35 LOT CRT vs. 35 conventional CRT patients were consecutively implanted according to current guidelines. All the patients had LBBB morphology QRS width of &amp;gt;150 ms. The two compared patient group did not show significant difference in age, gender, baseline non-ischemic etiology, LVEF, NYHA functional class, LBBB QRS width. Results Immediate postoperative results showed significantly increased QRS width reduction (p=.028) and at 6 months of follow-up a significantly greater improvement in LVEF(p=.031), NYHA functional class (p=.04) and Nt-ProBNP levels (p=0.043) were seen in LOT CRT patient group compared to conventional CRT patients. Conclusion Our single center observational study showed significant improvement in prompt postoperative QRS width and clinical follow-up parameters in LOT CRT implanted patients compared to conventional CRT implanted patients.LOTCRTvs.CRTQRSwidthreductionLOTCRTXray

Use of Levosimendan in patients with INTERMACS 3 profile: weaning from inotropic support and short- to medium-term evolution

Abstract Funding Acknowledgements None. Introduction Patients with advanced heart failure (HF) in cardiogenic shock (CS) present a markedly high mortality rate. For CS patients dependent on inotropes, management is difficult with few therapeutic options available, especially in the absence of a suitability for heart transplantation (HTX) or left ventricular assist device implantation (LVAD), thus associating an even worse prognosis. Purpose With our study we aim to analyse the rate of weaning from inotropic support when Levosimendan, a calcium sensitizer with positive inotropic effects, is used in INTERMACS 3 CS patients and their short to medium-term evolution. We then evaluate if the absence of right ventricular dysfunction, of renal dysfunction, non-ischemic aetiology and QRS width could be predicting factors of a successful weaning from inotropes. Materials and methods We conducted a monocentric retrospective analysis of patients from a tertiary cardiac intensive care unit that have received a 24 hours Levosimendan infusion in the context of INTERMACS 3 cardiogenic shock between August 2015 – April 2023. Results Of the 137 subjects included in the analysis, 62 patients received Levosimendan for INTERMACS 3 CS. The median age was 59±15.3 and 91.9% (n=57) were male. Baseline LVEF was 19±6%, cardiac index 1.67±0.4L/min/m2, median NTproBNP 13 378 ± 11 126ng/L. 51.6% (n=32) had ischemic heart disease and 40.3% (n=25) had dilated cardiomyopathy. After Heart Team discussion, only 37% (n=23) were considered eligible for HTX or LVAD. Successful inotrope weaning was experienced in 68% (n=42). Amongst patients with weaning failure, most outcomes resulted in either death (45%), ambulatory continuous Dobutamine infusion (30%), or benefited from a HTX if eligible (15%). The weaning failure rates were similar amongst patients eligible and non-eligible to HTX or LVAD with different outcomes after weaning failure as shown in Figure 1. The overall survival rates at 1 month and 6 months were of 83.8% and 53.2% respectively, with a significant difference between survival rates according to inotrope weaning success or failure as shown in Figure 2. We found no clinical, biological, or echocardiographic parameter to be significantly associated with an increased probability of weaning. Conclusion Levosimendan use in INTERMACS 3 CS patients provides a good rate of success in weaning from inotropic support and could be a useful tool in allowing treatment optimization and stabilization in non HTX or LVAD eligible patients, as well as being a "bridge to transplantation" alternative. No predicting factors for successful weaning have been identified.

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

Predicting One-Year Mortality after Discharge Using Acute Heart Failure Score (AHFS).

Background: Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods: This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results: During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76-0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59-0.77). Conclusions: The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis.