Left Ventricular Systolic Dysfunction Research Articles

Left ventricular dysfunction, pulmonary congestion, or both and cardiovascular risk after acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD), pulmonary congestion, or both are at increased risk for adverse cardiovascular events, including long-term heart failure. The EMPACT-MI trial studied the efficacy and safety of early initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in this population. We set out to evaluate the contemporary real-world risk associated with AMI presenting with LVSD and/or congestion and the projected impact of implementing early SGLT2i post-MI across the spectrum of risk. Purpose To evaluate the independent risk of presenting with LVSD, congestion, or both in patients with AMI. We will further explore the potential impact of the implementation of early initiation of SGLT2i in real-world clinical practice. Methods We conducted a retrospective population-based cohort study in Ontario, Canada, analyzing AMI hospitalizations from April 2009 to March 2022, emulating the EMPACT-MI trial cohort. Patients that survived to hospital discharge were stratified by baseline presentation with LVSD (defined as LVEF<50%), signs or symptoms of congestion or both and compared with a referent group without either risk factor (none). Exclusion criteria were previously established heart failure, prior SGLT2i use, eGFR < 20 ml/min/1.73m2 or chronic dialysis. The primary outcome was a composite of HF hospitalization or all-cause mortality at 30 days and 1 year. We used a multivariable logistic regression model to report an odds ratio (OR) and 95% confidence intervals (CI) adjusted for clinical risk factors. Results Among 36,837 AMI patients, 3% presented with congestion, 55% with LVSD, 10% with both, and 32% with none. Age/sex-adjusted 30-day event rates for the primary endpoint were 30%, 22%, 57%, and 7%, respectively. The corresponding adjusted ORs were 3.34 (95% CI: 2.05-5.46) for congestion, 3.58 (95% CI: 2.72-4.71) for LVSD, and 7.01 (95% CI: 5.09-9.65) for both, versus the reference group (none) (Figure 1). At year 1, a similar pattern of risk was observed (Figure 2). Based on the results of the EMPACT-MI trial being reported at the ACC conference in April 2024, relative and absolute risk differences in outcomes with implementation of early initiation of SGLT2i post-MI in real-world clinical practice across the spectrum of presentation will be reported. Conclusion Patients presenting with pulmonary congestion and/or LVSD remain at high risk of adverse cardiovascular events following AMI. This high-risk group represents an unmet need with a potential impact for improvement with novel interventions such as SGLT2i.

Five-year outcomes with self-expanding versus balloon-expandable transcatheter aortic valve replacement in patients with left ventricular systolic dysfunction

Abstract Background The importance of transcatheter heart valve (THV) design on clinical outcome in patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction remains unknown. Objectives We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve replacement (TAVR) with balloon-expandable vs. self-expanding THVs. Methods In an institutional TAVR registry, patients with LVEF <50% who underwent TAVR with either balloon-expandable or self-expanding THVs were included. A 1:1 propensity-score matching was performed to account for baseline differences between groups. Results A total of 759 patients were included between August 2007 and December 2022, and propensity-score matching resulted in 134 pairs. Technical success was achieved in over 85% of patients, and was similar in both groups. Self-expanding THVs were associated with a lower mean transvalvular gradient (7.1 ± 3.7 mmHg vs. 9.9 ± 4.3 mmHg; P <0.001) and a higher incidence of ³mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P <0.001) compared to balloon-expandable THVs. At 5 years, patients treated with a self-expanding THV had higher all-cause mortality than those with a balloon-expandable THV (67.8% vs. 55.8%, Adjusted Hazard Ratio: 1.44; 95% CI: 1.02-2.03; P = 0.037). There were no significant differences in other clinical outcomes up to 5 years between groups. Conclusions In the setting of LV systolic dysfunction, patients treated with a self-expanding THV had higher risk of 5-year mortality compared to patients treated with a balloon-expandable THV.

The relationship between coronary microvascular dysfunction and left ventricular longitudinal systolic function in patients with diabetes mellitus

Abstract Background Coronary microvascular dysfunction (CMD) often accompanies diabetes mellitus (DM), leading to myocardial ischemia despite normal or mildly narrowed coronary arteries (<50% stenosis). CMD causes myocardial hypoperfusion, resulting in impaired systolic function. Coronary flow reserve (CFR) serves as a marker of microvascular function, particularly in the absence of significant epicardial coronary stenosis. Myocardial contrast echocardiography (MCE) is a key tool for clinically assessing CFR. Global longitudinal strain (GLS) derived from two-dimensional speckle tracking echocardiography (2D-STE) offers early insights into left ventricular systolic dysfunction during subclinical stages but is underexplored in diabetic CMD patients. Objective This study aimed to assess myocardial microcirculatory dysfunction in diabetic patients using stress myocardial ultrasound enhancement imaging, investigate its relationship with left ventricular longitudinal systolic function, and evaluate the utility of 2D-STE in assessing left ventricular systolic function in CMD patients. The findings provide insights for early detection and prevention of left ventricular longitudinal systolic dysfunction in diabetic patients with myocardial microcirculatorydysfunction. Methods Seventy type 2 diabetic patients who underwent coronary CT or angiography within the past three months without obstructive coronary artery disease were included. Clinical data, biochemical parameters, and blood glucose levels were collected. Left ventricular longitudinal strain indices were obtained using 2D-STE, and microvascular function was assessed based on CFR measured via transthoracic stress MCE. Patients were categorized into CMD (CFR<2) and control (CFR≧2) groups, with clinical and echocardiographic parameters compared. Strain parameters included GLS at rest, GLS under stress, and ∆GLS. Correlations between these indices and CFR were analyzed. Results 1. Seventy patients, with 41 males (41.4%) and 58 females (58.6%), averaging 56.14±10.84 years, were included. The mean BMI was 25.53±3.40. Among them, 23 patients were smokers (32.8%), 41 had hypertension (58.6%), and 36 had hyperlipidemia (51.4%). 2. Patients in the CMD group had significantly shorter diabetes duration (6.59±2.18 years vs. 8.13±2.17 years) and lower glycosylated hemoglobin (7.99±1.52% vs. 8.78±1.55%) (P<0.05). No significant differences were observed in other parameters. 3. GLS and ∆GLS differed significantly between groups, while other echocardiographic parameters did not. 4. Logistic regression analysis identified GLS as an independent predictor of CMD in diabetic patients under stress. Conclusions 1. Diabetic patients with CMD exhibit lower GLS and ∆GLS under stress, indicating early reductions in left ventricular systolic function reserve. 2. 2D-STE can detect early left ventricular systolic impairment in diabetic patients.MCE quantitative analysisGLS in normal and CMD group

Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction

Abstract Introduction Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown. Purpose To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction. Methods We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of <50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data. Results A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p <0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p <0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p <0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p <0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass. Conclusions The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.

Artificial intelligence for automated left ventricular systolic dysfunction detection using a wearable cardiac patch incorporated with synchronized phonocardiogram and electrocardiogram

Abstract Background Left ventricular systolic dysfunction (LVSD) is characterized by a reduced left ventricular ejection fraction (LVEF) and is associated with three times the risk of developing Heart failure (HF). We aimed to test an artificial intelligence (AI) algorithm applied to synchronized phonocardiography (PCG) and electrocardiography (ECG) signals, recorded with a wearable device, to validate its potential as a screening tool for LVSD. Methods Using ECG and PCG data collected from 1960 admitted patients in a hospital, we trained an AI algorithm to detect the LVSD. There are two ways of defining LVSD, one group is defined by LVEF <50% and the other is defined by LVEF 40% as measured by echocardiography. The AI algorithm followed a two-step detection structure. In the first phase, ECG signals were processed by wavelet denoising and baseline wander correction, and PCG signals were converted to the frequency domain via wavelet transformation. We developed a 1D CNN-based U-Net variant model to pinpoint electromechanical activation time (EMAT). Addressing the challenge of processing multimodal signals, we devised a contrastive learning approach that mandates the encoders for different modalities to generate embeddings within the same feature space. This trained encoder, along with the decoder in U-Net, is subsequently fine-tuned for EMAT detection. The AI-EMAT% was obtained by adjusting detected EMAT based on RR interval. For the second phase, random forest regression is used to estimate LVEF, incorporating features such as AI-EMAT% and clinical data, including age and gender. For LVSD detection, we evaluated the performance of methods by bifurcating AI-estimated LVEF% (AI-predict LVEF%) based on thresholds of 40% and 50%, and by directly estimating AI-EMAT% cutoff. The evaluation of LVSD detection algorithm, conducted via 2-fold cross-validation, involves dividing the dataset into two subsets, with each alternately serving as training and testing sets to ensure a fair assessment. Results We recruited 1960 patients (1430 [72.96%] male). 357 (18.21%) had an ejection fraction of 50% or lower, and 157 (8.01%) had an ejection fraction of 40% or lower. In detecting LVSD of LVEF<50%, AI-EMAT% yielded an AUROC of 0.86, sensitivity of 73.7%, and specificity of 80.7%. While AI-predict LVEF% approach resulted in an AUROC of 0.89, sensitivity of 81.8%, and specificity of 81.5%. In detecting LVSD of LVEF<40%, AI-EMAT% yielded an AUROC of 0.89, sensitivity of 85.4%, and specificity of 76.0%. While AI-predict LVEF% outputs resulted in an AUROC of 0.91, sensitivity of 92.4%, and specificity of 76.8%. Conclusions We developed an automated algorithm to detect LVSD using a wearable device that incorporated synchronized PCG and ECG signals, demonstrating robust performance across different subgroups. This approach represents a strategy for automated screening of LV systolic dysfunction, particularly beneficial in resource-limited settings.Baseline and AUROCAI algorithm

Contractile reserve is associated with response to catheter ablation in patients with atrial fibrillation and left ventricular systolic dysfunction

Abstract Background Although patients with atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) can benefit from catheter ablation, some patients do not respond. Prospectively identifying responders is challenging. Contractile Reserve (CR) on Exercise Stress Echocardiography (ESE) has demonstrated stratifying value before cardiac resynchronisation therapy but has not been evaluated in the setting of AF. Objective To evaluate whether CR on ESE was associated with response to CA in patients with LVSD. Methods Patients with persistent AF and LVSD (LVEF <50%) undergoing first-time catheter ablation were enrolled in the AFHF study. Patients underwent trans-thoracic echocardiography at rest and maximum exertion using a recumbent cycle ergometer. CR was the difference in LVEF at maximum exertion versus rest. Echocardiography was repeated six months after successful catheter ablation to determine Response based on the Universal Definition of Heart Failure improvement (LVEF +10%, or if baseline LVEF >40% then LVEF>50%). Results 52 patients were enrolled with baseline demographics in Table 1. 39 patients completed follow-up with 32 (82%) being responders. Responders had greater CR than non-responders (+10% (+5, +12) vs 3% (0, +4), (p=0.008)). A CR ≥ 5% had a positive predictive value of 0.96 for Response in this cohort. The AUROC was 0.83 with a specificity of 0.86. This was also associated with significant improvement in reported Minnesota living with HF scores (p<0.01). Conclusion CR was associated with response to CA in patients with persistent AF and LVSD in this exploratory analysis. Validation in an external cohort is needed to evaluate fit before prospective evaluation of its clinical utility.Baseline CharacteristicsROC curve for response to ablation

Myocarditis in the modern era: analysing the impact of high-sensitivity troponin & C-reactive protein in predicting the extent of myocarditis and LV systolic dysfunction on cardiac magnetic resonance

Abstract Background The diagnostic yield of acute myocarditis has improved considerably since the advent of high-sensitivity troponin (hs-Tn) assays and adoption of the 2018 Lake Louise criteria for cardiac magnetic resonance (CMR)-based imaging for myocardial oedema and injury (1). Yet, a seminal 1997 study, predating these technological advances, remains widely cited for highlighting an absence of troponin rise in two-thirds of myocarditis cases (2). We hypothesize that all cases of myocarditis exhibit hs-Tn rise. However, whether such elevations in hs-Tn or inflammatory markers correlate with the extent of myocardial injury and left ventricular systolic dysfunction (LVSD) on CMR remain unclear. To provide insight into this, we examined a contemporary cohort of cases between 2019-2023. Methods Two authors independently conducted case-notes reviews to verify the diagnosis of myocarditis. CMR findings were stratified into regional (e.g. inferolateral) and global myocarditis (e.g. subepicardial LGE in all segments). This classification aimed to explore potential correlations with LVSD severity, peak hs-Tn and other inflammatory markers. Receiver operating characteristics (ROC) curves was calculated to determine any cut-off value for predicting CMR findings and adverse patient outcomes. Results 103 inpatients were clinically coded as ‘myocarditis’ upon discharge, but subsequent CMR (within 4 weeks) reclassified 23 patients into other causes (Figure 1). Analysis of the myocarditis cohort revealed a predominantly male population (76%) with median age 53, commonly presenting with chest pain without a viral prodrome (Figure 2A-D). Elevated hs-Tn levels were observed universally, with a median peak hs-TnT of 610ng/L (IQR 1081.5ng/L) and hs-TnI of 3820ng/L (IQR 12416ng/L). In contrast, peak CRP ranged between 2mg/L (normal) and 600mg/L. Global myocarditis was detected in 11/80 patients (13.8%); however, this finding did not correlate with adverse patient outcomes which included all-cause mortality (9.6%) and cardiac re-admissions within 12 months (9.6%, namely for chest pains). No arrhythmic deaths were noted. COVID was present in 4% on admission. CRP cut-off of 140mg/L predicted the occurrence of global myocarditis with a sensitivity of 72.7% and specificity of 87.0% (AUC 0.74, 95% CI 0.52-0.96, p=0.014) (Figure 2E). However, neither hs-Tn or CRP levels correlated with the degree of LVSD (Figure 2F) or adverse outcomes. This is likely limited by the small sample. Conclusion Although all cases of myocarditis exhibited raised hs-Tn, this did not correlate with the degree of LV systolic impairment on CMR. Myocarditis with regional LV involvement can have normal CRP levels, while a CRP cut-off >140mg/L may predict the occurrence of global myocarditis. However, CMR stratification into regional and global was not associated with adverse patient outcome within 12 months. A larger sample size is required to verify this finding, including longer term follow-ups.Flowchart of patients included in studyMain findings

The prognostic impact of inducible ischemia in severe ischaemic cardiomyopathy: a randomised comparison of medical therapy and revascularisation

Abstract Background The presence of inducible myocardial ischaemia is used to select patients with stable coronary artery disease for revascularisation, based on observational data in patients with preserved left ventricular function. It is unclear if identification of a substrate for ischaemia is prognostic in patients with severe ischaemic left ventricular systolic dysfunction (LVSD). Purpose To determine if the extent of inducible ischaemia by stress perfusion CMR relates to clinical outcomes and/or the response to revascularisation in patients with ischaemic LVSD. Methods Patients enrolled in the REVIVED-BCIS2 randomised trial were eligible for inclusion if they had undergone stress perfusion CMR prior to randomisation (1). Visual assessment of myocardial perfusion and late gadolinium enhancement (LGE) was performed by an independent core laboratory, by consensus of two expert readers who were blinded to trial-group assignment and clinical or outcome data. For this analysis, segmental ischaemia was classified in a binary manner and the overall volume of ischaemia is expressed in relation to total LV mass, defined as [number of ischaemic segments]/16 * 100. The primary composite outcome was all-cause death or aborted sudden death. Secondary outcomes included left ventricular ejection fraction change at 6 and 12-months, cardiovascular death and sustained ventricular arrhythmias. Data are presented as median [IQR] or mean ± standard deviation. Results Of 700 participants enrolled, stress perfusion CMR was acquired in 200, 181 of whom had scans of sufficient quality for core laboratory analysis (91 randomised to percutaneous coronary intervention and 90 to optimal medical therapy; age 69±8 years, 86% male, 40% diabetic, baseline jeopardy score 10 [8-12]). On CMR, LVEF was 28±8%, scar burden was 18% [9-26] and ischaemic burden was 31% [13-56]. There was no association between ischaemic burden and the primary outcome (HR 1.0, p=0.997, CI 0.92-1.09) or any of the secondary outcomes (Figure 1). There was no relationship between ischaemia and randomised treatment group (Figure 2). Conclusion The REVIVED-BCIS2 trial incudes the largest cohort to date of stress perfusion CMR in severe LVSD, randomised to relief of ischaemia or medical therapy alone. In this study, ischaemic burden was not associated with clinical outcomes or the outcome following revascularisation.Figure 1 – HRs for 10% ischaemic burdenFigure 2 - KM plots for primary outcome

Acute renal failure in patients with infective endocarditis

Abstract Background/Introduction Acute kidney failure (AKF) appears in a high percentage of patients with infective endocarditis (IE), becoming a complication related to the mortality of the disease and delayed recovery of patients. Purpose To investigate the factors that are related to the development of AKF in patients with IE. Methods Study of all cases of IE consecutively diagnosed in an university hospital between 2005 and 2021. A disease extension protocol was carried out using imaging tests and the levels of potentially nephrotoxic antibiotics were monitored. Furthermore, starting in 2010, a multidisciplinary committee (MC) was created to follow patients with EI. Factors potentially related to the development of AKF during hospital admission according to RIFLE criteria were analyzed using a binary logistic regression analysis. Results 305 cases were included, 96.7% of them meeting definitive IE criteria. The median age was 66 (54-74.5) years, 75.4% male. The most frequent microorganism was S. aureus (66; 21.6%), 172 (56.4%) underwent surgery and 107 patients (35.1%) died. 149 cases (45.3%) developed AKF, with no differences before (45.3%) and after the creation of the CM. The variables related in the multivariate analysis to the appearance of AKF were age (OR 1.01; 95% CI: 1.01-1.05; p= 0.006), baseline creatinine (OR= 1.53; 95% CI = 1.22-1.68; p<0.001). ), peripheral embolism (OR=1.86; 95% CI = 1.07-3.22; p= 0.027), the development of heart failure (OR=1.98; 95% CI = 1.12-3.22; p= 0.017) and left ventricular systolic dysfunction (OR= 4.02; 95% CI = 1.09-14.85; p= 0.037). None of the other variables analyzed, including the type of microorganism and the use of nephrotoxic antibiotics, were related to the development of AKF. Conclusions In a hospital center with a protocol for the study and treatment of infective endocarditis, the development of AKF is related to age, baseline creatinine, peripheral embolism, and the development of heart failure.

Differences in risk profiles and clinical outcomes according to age in patients with high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Temporal declines in rates of rehospitalization and death after acute myocardial infarction (MI) have not been uniform across age groups. A better understanding of how risk profiles and clinical outcomes differ after MI by age may allow for targeted treatment and prevention strategies. Aims To investigate risk profiles and clinical outcomes following high-risk MI according to age in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Adults without prior heart failure (HF) were randomized to sacubitril/valsartan versus ramipril within 0.5 to 7 days of a MI complicated by transient pulmonary congestion and/or left ventricular systolic dysfunction and additional risk-augmenting factors. Associations between age and clinical outcomes were analyzed using Cox proportional hazards regression models, which were additionally adjusted for baseline demographic and clinical covariates (Figure). Results The mean age of the 5,661 PARADISE-MI participants was 64 ± 11 years. Patients aged ≥75 years (n=1051) were more likely women, had more hypertension and atrial fibrillation and lower estimated glomerular filtration rate, were less likely to present with ST-segment elevation MI and regardless of type of MI were less likely to receive primary reperfusion and guideline-based medical therapy (Table). Age was significantly associated with all-cause death (HR 1.54 per 10-year increase; 95% CI, 1.41-1.68) and was more strongly associated with non-CV death (HR 2.09; 95% CI, 1.70-2.56) than with CV death (HR 1.43; 95% CI, 1.29-1.57). Age was also associated with incident HF (HR 1.37; 95% CI, 1.25-1.49) (Figure). Multivariable adjustment attenuated the risk relationship of age with recurrent fatal or non-fatal MI (HR 1.08; 95% CI, 0.96-1.21) and the coronary composite outcome (HR 1.01; 95% CI, 0.93-1.09). The relative treatment effect of sacubitril/valsartan versus ramipril on the primary composite outcome of CV death or incident HF was not significantly modified by age (p-interaction = 0.19). Conclusions Following high-risk MI, age was most strongly associated with subsequent non-CV death followed by CV death and incident HF, but was not independently associated with recurrent coronary events. The heightened risk of CV death and HF with advancing age was not explained by differences in clinical characteristics. Older patients may require closer surveillance and more aggressive treatment after MI to mitigate the elevated risk of CV death and HF.

Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population

Abstract Background Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies. Purpose Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD. Methods The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index. Results Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a >5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68). Conclusion Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.

HIV is associated with subtle impairments in left ventricular function: insights from a large prospective cohort study of well-treated people with HIV

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <50% or absolute global longitudinal strain (GLS) <16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’>14, (2) septal e’ velocity < 7 cm/s or lateral e’ velocity <10cm/s, (3) tricuspid regurgitation velocity >2.8 m/s, (4) left atrial volume index >34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p<0.001], E/A ratio [1.0 vs. 1.2, p<0.001] and average e’ [9.5 vs. 10.5 cm/s, p<0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Preventing unnecessary echocardiograms in de novo patients referred to the cardiology outpatient clinic using electrocardiogram-based deep learning

Abstract Introduction The growing demand on European echocardiography labs, driven by the rise in structural heart disease (SHD), is further complicated by a shortage of skilled sonographers, necessitating resource optimisation strategies. Electrocardiogram (ECG)-based deep learning models may assist in streamlining the echocardiography workflow. Purpose This study sought to develop a deep learning model capable of identifying patients at very low risk of SHD in a population of de novo patients referred to the cardiology outpatient clinic. Methods We identified all adult patients who underwent a 12-lead ECG and echocardiogram at a Dutch academic teaching hospital between 2011 and August 2023. Echocardiogram outcomes were extracted from reports, including left ventricular systolic dysfunction (LVSD), left ventricular dilatation (LVD), aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR), and tricuspid regurgitation (TR), from which a composite outcome label was derived. A cohort of patients newly referred to our cardiology outpatient clinic with a primary complaint of chest pain, dyspnea, palpitations, dizziness, a murmur, or an abnormal ECG was held out as a test set, while the remaining dataset was split patient-wise into training (90%) and validation (10%) sets. A convolutional neural network was trained using only the ECG tracing as input and the composite label as outcome. Results We included 92,210 ECG-echo pairs from 44,785 patients (19,717 female) with 25,543 (27.7%) abnormal ECG-echo pairs. Among 2724 newly referred patients in the test set, 210/1389 males (15.1%) and 201/1335 females (15.1%) were diagnosed with SHD. In the test set, the model for predicting composite outcome demonstrated an area-under-the-curve, negative predictive value, and specificity of 0.74 (95% confidence interval [CI] 0.71-0.79), 0.94 (95% CI 0.92-0.95), and 0.47 (95% CI 0.45-0.49), respectively. Conclusion This study demonstrates the feasibility of employing deep learning models based solely on electrocardiogram (ECG) data to identify patients at very low risk of structural heart disease (SHD). Further validation and prospective studies are warranted to confirm the generalizability and clinical utility of our findings in diverse patient populations and healthcare settings.

Prospective longitudinal evaluation of AI-ECG in newly diagnosed heart failure (PLANE-HF)

Abstract Background * In the United Kingdom, there are one million people suffering from heart failure (HF), with more than 60,000 new cases annually (1). * Monitoring for declining left ventricular ejection fraction (LVEF) could optimise treatment approaches and avert healthcare episodes. * Easy home-based tracking of cardiac function would be transformative. * Previous studies have validated the capability of artificial intelligence-enabled electrocardiogram (AI-ECG) to correlated with changes in LVEF (2). * We hypothesize that longitudinal changes in AI-ECG probability score is associated with changes in the left ventricular (LV) function. Method * A prospective multicentre longitudinal study recruiting newly diagnosed HF with reduced ejection fraction (HFrEF) cases to investigate application of AI-ECG using longitudinal single-lead ECG recordings via patient-administered smart ECG-stethoscope examination – Figure 1. * A total of 36 patients were included in the analysis, with invitation to return for repeat echocardiography at 6-8 weeks. * Adjusted logistic regression was performed to analyze changes in LVEF by 10% as the outcome variable, investigating the relationship with the trajectory of AI-ECG probability scores. This study was approved by the UK Health Research Authority (reference 22/LO/0701). Result * Out of 36 patients, 19 patients had ischaemic and 17 had a non-ischaemic HF. * The mean age was 56.3 years, 97.2% patients were male and 46.6% were White. * 328 longitudinal single-lead ECGs were captured and used in the analysis. * 12 (33.3%) patients had an increase of their LVEF by 10%; preceding AI-ECGs was predictive of this recovery (OR 1.36; 95% CI, 1.05 – 1.65, p value = 0.016 – Table 1) Clinical Importance: * Individualised predictions of deterioration and improvement * Proactive medication adjustment * Enhanced triage for echocardiography Conclusion * AI-ECG designed to identify left ventricular systolic dysfunction (LVSD) can predict changes in LVEF% among newly diagnosed HFrEF patients. * Such results can place AI-ECG as a remote monitoring tool to track improvement or deterioration in patients’ LVEF%, which facilitate a proactive management and prevention strategies.

Artificial intelligence applied to electrocardiographic images for the risk stratification of cancer therapeutics-related cardiac dysfunction

Abstract Background Traditional risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability and affordability. Purpose To examine an artificial intelligence (AI)-enhanced electrocardiographic (AI-ECG) surrogate for imaging-based risk biomarkers, and its association with CTRCD. Methods Between 2013-2023, across 5 hospitals of a large U.S.-based health system, we identified patients with breast cancer or non-Hodgkin lymphoma (NHL) who received anthracyclines (AC) and/or trastuzumab (TZM), as well as a (negative) control cohort of patients receiving immune checkpoint inhibitors (ICI). We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to ECG images (≥0.1=positive screen) (ref 1) and explored the association between the model’s predictions and: i) global longitudinal strain (GLS) measurements within 15 days; ii) future CTRCD (defined as a new cardiomyopathy, heart failure, or left ventricular ejection fraction (LVEF) decrease to <50%), as well as a more specific secondary outcome of LVEF decrease <40%. In a negative control analysis of patients receiving ICI, we correlated baseline AI-ECG LVSD predictions with downstream myocarditis. Results Higher AI-ECG LVSD predictions were associated with progressively worse GLS (-18% [IQR: -20 to -17%] for AI-ECG predictions <0.1, to -12% [-15 to -9%] for ≥0.5, p<0.001, n=7,271) (A). In 1,308 patients receiving AC/TZM (age 59 [IQR 49-67] years, 999 [76.4%] women, 80 [IQR 42-115] follow-up months) a positive baseline AI-ECG LVSD screen was associated with higher incidence of CTRCD (n=404 events, adjusted HR 2.22 [95%CI: 1.63-3.02]) and/or LVEF <40% (n=72 events, adjusted HR 4.76 [95%CI: 2.62-8.66]) (B). In a negative control analysis of 2,056 patients receiving ICI (age 65 [IQR 57-73] years, 913 (44.4%) women, follow-up 63 [IQR 28-99] months) AI-ECG predictions were not associated with downstream myocarditis (adjusted HR 1.36 [0.47-3.93]). Conclusions AI applied directly to baseline ECG images may stratify the risk of CTRCD associated with anthracycline or trastuzumab exposure.

Development of machine learning models for prediction of left ventricular systolic dysfunction in patients with isolated left ventricular dilation

Abstract Background/Introduction Isolated left ventricular dilation (ILVD), in the absence of concomitant LV systolic dysfunction, is a risk factor for new reduction in LV ejection fraction (LVEF) and adverse clinical outcomes. We assessed the performance of different machine learning (ML) models in predicting new reduction in LVEF in patients with ILVD. Methods A retrospective analysis of de-identified patient records in the Tempus Database with at least two transthoracic echocardiograms (TTE) conducted between January 2019 and December 2022 were retrospectively analyzed, with the follow up period ending in January 2023. Inclusion/exclusion criteria are shown in Figure 1A. Briefly, patients with ILVD were defined based on echocardiographic parameters as those with LVEF > 50% and LV end diastolic volume indexed (LVEDVi) > 62 mL/m2 for females and > 75 mL/m2 for males, without prior LVEF < 50% and/or grade 2/3 diastolic dysfunction. The endpoint was LVEF < 40% on future (≥90 days) TTE. Five hard voting ML models and one soft voting ensemble model were trained with data parsed from TTE reports (Figure 1B). Feature importance (SHAP) was calculated, and receiver operating characteristic (ROC) and Kaplan Meier curves evaluated the final model (Figure 1C-E). Results A total of 2,962 patients met the inclusion criteria. The median time from index to last TTE was 578 (IQR = 500) days. LVEF < 40% on follow up TTE was noted in 6% of patients (177 patients, median 478 days to endpoint, IQR = 535 days). Of the six models developed, the ensemble model had the highest ROC area under the curve (0.791, Figure 1D), precision (0.163), F1-score (0.266), and specificity (0.773). The ensemble model also had the lowest predicted prevalence (25.5%), although this was higher than the observed prevalence in the test set (5.7%). Patients predicted to develop LVEF < 40% had a 8.2x higher risk of developing LVEF < 40% within five years of index (p<0.001, Figure 1E). Feature importance showed that male gender, higher heart rate, lower LVEF at index TTE, higher LVEDVi, and lower tricuspid annular plane systolic excursion had the highest mean absolute impact on the model’s output probability (Figure 1C). Conclusion Using only data parsed from the index TTE, ensembling a model for the prediction of developing LVEF < 40% in patients with ILVD and without a history of LV diastolic or systolic dysfunction performed the best. Additional analyses including clinical variables such as comorbidities, symptoms, and medications may improve the model’s performance.

The development and long-term maintenance of heart failure with improved ejection fraction after a heart failure hospitalization: how are mortality rates affected?

Abstract Background According to the current ESC HF Guidelines (GLs), the implementation of the guideline-directed medical therapy (GDMT) is of strategic importance in heart failure (HF) with reduced ejection fraction (HFrEF). In the effect of the successful implementation of the modern GDMT, significant improvement in terms of the left ventricular ejection fraction (LVEF) might be expected in HFrEF. Hence, a new HF category, the improved ejection fraction (HFimpEF), was introduced in the current ESC HF GLs, which has come to the spotlight in the recent years. However, its course and long-term prognosis are still not clearly understood. Aim To assess the development and long-term maintenance of the HFimpEF category among a consecutive patient cohort requiring hospitalization due to HFrEF, evaluate its effect on prognosis, and examine the independent predictors of its development. Patients and methods A retrospective analysis was carried in a real-world cohort of 270 HFrEF patients (male: 77%, age: 61[49-68]years, coronary artery disease: 47%, diabetes: 30%, hypertension: 60%, atrial fibrillation: 35%, LVEF: 25[20-30]%, eGFR at admission: 59[45-73]mL/min/1.73m², NT-proBNP at admission: 4733[2368-9711]pg/mL, SBP: 120[107-135]mmHg) hospitalized for HF in 2019-2023 at two tertiary cardiac centers. At admission the complex modern GDMT of HFrEF had been already introduced (RASi[ACEi/ARB/ARNI]: 61%, βB: 63%, MRA: 47%, SGLT2i: 6%) in the minority of the cohort. The improvement to the HFimpEF category was examined after the therapy optimization (OMT). All-cause mortality (ACM) rates were evaluated with Kaplan-Meier method and the predictors of the development to HFimpEF category were assessed with logistic regression analysis. Results In the total cohort at discharge, a high proportion of patients received RASis (94%), βBs (90%), MRAs (97%), and SGLT2is (35%). 79 patients (29%) evolved to the HFimpEF category after OMT. During the median 810 [456-1161] days of follow-up (FU), HFimpEF patients had lower, but unquestionably still increased mortality rates (29% vs. 10%, p=0.001; non-HFimpEF vs. HFimpEF patients). At two years of the FU period, based on the available echocardiographies, 98 % of the patients remained in the HFimpEF category. After performing a multivariate logistic regression analysis, the severity of the LV systolic dysfunction (LVSD) and the „de novo" diagnosis of HFrEF proved to be independent predictors of the development of the HFimpEF category. Conclusions In the effect of the implementation of GDMT, a significant proportion (29%) of our multimorbid, hospitalized HFrEF patient cohort improved to the HFimpEF category. The predictors of its development were the severity of the LVSD and "de novo" HFrEF diagnosis. During the FU period, most of the HFimpEF patients remained in this category. However, their persistently elevated mortality rates raise the awareness of the importance of the conscious application and maintenance of GDMT.

Right ventricular myocardial work: a step forward for the assessment of right ventricular to pulmonary artery coupling

Abstract Background Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function. By integrating RV global longitudinal strain as systolic function parameter, pulmonary systolic and diastolic pressures as afterload indices, and pulmonary and tricuspid valves timings, RVMW could provide a more comprehensive evaluation of RV function. Purpose The aim of this study was to assess patterns of RVMW indices in patients with preserved and impaired RV to pulmonary artery (PA) coupling (RVAC), as assessed by RV free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) ratio. Methods We studied by echocardiography 158 consecutive patients with stable HF and left ventricular (LV) systolic dysfunction (LV ejection fraction < 50%). RVAC was assessed by RVFWLS/PASP and patients were grouped according to the median value. Four parameters of RVMW were obtained: RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW) and RV global work efficiency (RVGWE). Results According to RVFWLS/PASP ratio, patients were divided into two groups: A) preserved RVAC (RVFWLS/PASP ratio ≥ 0.51; N=84) and B) impaired RVAC (RVFWLS/PASP ratio < 0.51; N= 74). Both RVGWI (371±156 vs 384±207 mmHg%, P=NS) and RVGCW (449±171 vs 516±249 mmHg%, P=NS) did not significantly differ between the two groups (figure 1). However, group B (impaired RVAC) showed significantly greater RV wasted work (94±69 vs 44±30 mmHg%, P=0.0001) and significantly lower RV work efficiency (80±13 vs 88±8 %, P=0.0001) compared to group A (preserved RVAC, figure 2). Conclusions RVMW provided new insight in the RV function assessment, highlighting lower efficiency due to higher wasted work in RV to PA uncoupled patients.Figure 1Figure 2

Prevalence and prognostic significance of restriction versus systolic dysfunction in patients with transthyretin and light chain cardiac amyloidosis

Abstract The tenet of cardiac amyloidosis (CA) as a paradigm of heart failure with restrictive ventricular physiology and preserved systolic function has come under scrutiny. Thus, we aimed to evaluate the prevalence and clinical significance of left ventricular (LV) systolic dysfunction versus restriction in a large real-world cohort with CA, assessed at the time of diagnosis. Methods This is a multicenter retrospective analysis including 540 transthyretin (ATTR)-CA and 280 light chain (AL)-CA. Patients were divided into 3 phenotypes: 1) preserved LV function: LV ejection fraction (EF) ≥50% associated with grade 0/I diastolic dysfunction; 2) restriction: LV-EF≥50% associated with grade II/III diastolic dysfunction; 3) systolic dysfunction: LV-EF<50% irrespective of diastolic function. We analysed progression from preserved LV function towards the other two phenotypes and their survival. Results In ATTR-CA, prevalence of preserved LV function was 27%, restriction was 44% and systolic dysfunction was 28%. Among patients with preserved LV function, annual conversion rate to restriction was 24% and to systolic dysfunction was 17%. At 3 years, survival free from all-cause mortality was 88%, 76% and 63% respectively (figure A). In AL-CA, prevalence of preserved LV function was 30%, restriction was 49% and systolic dysfunction was 20%. Among patients with preserved LV function, annual conversion rate to restriction was 28% and to systolic dysfunction was 8%. At 3 years, survival free from all-cause mortality was 56%, 39% and 29% respectively (figure B). Conclusions Restriction was the presenting phenotype in less than half of patients, while systolic dysfunction in approximately one quarter. The annual rate of progression form preserved LV function towards restriction or systolic dysfunction was high. In ATTR systolic dysfunction was associated with worse outcome, compared to restriction; in AL both restriction and systolic dysfunction were associated with equally ominous outcome.

Sodium-glucose cotransporter 2 inhibitor attenuates left ventricular dysfunction in post-myocardial infarction in rats via reducing cardiac mitochondrial impairment

Abstract Background Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a class of antidiabetic drugs that has demonstrated cardiovascular benefits in heart failure patients, regardless of diabetic status. Although current evidence regarding the role of SGLT2i in myocardial infarction (MI) is still limited, a recent randomized study reported the favorable effects of dapagliflozin on cardiometabolic outcomes in post-MI patients. Nevertheless, the evidence of the underlying mechanism of SGLT2i in post-MI is still unclear. Purpose We aimed to investigate the cardioprotective effects and cellular mechanisms of SGLT2i in post-MI rats. Methods 72 male Wistar rats were divided into two groups: the MI group, which underwent surgery involving permanent ligation of the left anterior descending coronary artery to induce MI (n=58), and the sham group, which underwent a sham operation (n=14). One-week post-surgery, echocardiography was performed. For inclusion in the MI group, only rats exhibiting anterior wall akinesia and a left ventricular ejection fraction (LVEF) < 50% were considered. Subsequently, MI rats were stratified into three groups to receive different interventions: 1) MI+VEH (distilled water, PO, n=13), 2) MI+DAPA (dapagliflozin, 1 mg/kg, PO, n=11), and 3) MI+ENA (enalapril, 10 mg/kg, PO, n=14). After 8 weeks of treatment, echocardiography was performed again. Then, the rats were sacrificed, and heart tissues were used to determine mitochondrial function and protein expressions. Results After 8 weeks of treatment, the MI+VEH group exhibited a decrease in LVEF compared to the sham group (Fig. 1A). The MI+VEH group was associated with cardiac mitochondrial dysfunction, as indicated by increased mitochondrial oxidative stress, mitochondrial membrane depolarization, and mitochondrial swelling, and impaired mitochondrial biogenesis, as indicated by decreasing peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions (Fig. 1B-F). Treatment with dapagliflozin and enalapril effectively attenuated left ventricular (LV) systolic dysfunction, reversed mitochondrial dysfunction, and restored mitochondrial biogenesis induced by MI (Fig. 1A-F). Conclusion SGLT2i could attenuate LV dysfunction and restore mitochondrial dysfunction in post-MI rats. These findings demonstrate SGLT2i as a novel cardioprotection against post-MI complications.