Left Ventricular Systolic Dysfunction Research Articles

Abstract 4130756: Two Leads are All We Need: Optimizing Choice of Electrocardiogram Leads for Artificial Intelligence-based Based Detection of Left Ventricular Systolic Dysfunction

Introduction: Artificial intelligence (AI) models built with convolutional neural networks (CNN) accurately detect left ventricular systolic dysfunction (LVSD) from 12-lead electrocardiogram (ECG). While AI models can also detect LVSD from 1-lead (but with lower accuracy), the optimal numbers and combinations of the leads remain unclear. Aims: To identify the optimal numbers and combinations of ECG leads for detecting LVSD. Methods: A total of 75,033 ECGs recorded within 14 days of an echocardiogram were collected. The data was randomly divided into derivation, validation, and test sets in a 5:2:3 ratio without patient overlap. The same split was used throughout the study. While all available ECGs were included in derivation and validation sets, the test set included 1 ECG per patient closest to the echocardiogram. CNN models were trained to detect LVSD, defined as left ventricular ejection fraction <40%, using all possible combinations of 1-, 2-, and 3-lead extracted from 12-lead ECG. The final model for each lead combination was chosen according to the area under the receiver operating curve (AUROC) on the validation set across the 20 epochs. The models were trained 4 times to evaluate the variance caused by initialization vectors. Results: The 12-lead model showed AUROC of 0.893 (95%CI, 0.887-0.899). Multiple models trained with 2-lead achieved similar performance, with aVR-V4 displaying the highest AUROC (0.892; 95%CI, 0.889-0.895), followed by I-V4 (0.889; 95%CI, 0.883-0.895) and I-II (0.888; 95%CI, 0.884-0.893). The results were similar for 3-lead (aVR-aVL-V4: AUROC 0.895; 95%CI, 0.893-0.897, I-aVR-V4: 0.892; 95%CI, 0.889-0.896, and I-II-V4: 0.891; 95%CI, 0.886-0.895). The choice of leads greatly affected the performance. For the 1-lead models, aVR showed the highest AUROC (0.876; 95%CI, 0.873-0.879), but III only achieved an AUROC of (0.766; 95%CI, 0.761-0.772). The combinations, including a chest lead and a limb lead (especially aVR), tend to achieve higher performance (Fig 1). Conclusion: A combination of 2-lead was sufficient to achieve comparable accuracy as the 12-lead for the AI model to detect LVSD. Wearable devices collecting a combination of a limb and a chest lead may enhance the detection of LVSD.

Abstract 4144528: The Polygenic Mechanisms of Dilated Cardiomyopathy Contribute to The Development of Tachycardia-Associated Cardiomyopathy in Patients With Atrial Tachyarrhythmias

Background Longstanding tachycardia can lead to reversible left ventricular (LV) systolic dysfunction called tachycardia-associated cardiomyopathy (TAC). It is unknown if there is a genetic predisposition to the development of TAC or whether there is overlap between the genetic pathways of TAC and dilated cardiomyopathy (DCM). Research Questions Is there a genetic predisposition towards the development of TAC in individuals with arrhythmia? If so, do these genetic pathways overlap with those of DCM? Methods/Approach The study is a single-center case control study performed at the Montreal Heart Institute (MHI). Inclusion criteria for TAC cases are shown in Table 1. All cases underwent array genotyping and exome sequencing. Previously genotyped controls with arrhythmia but no documented LV dysfunction were included from the MHI Biobank. Following imputation using the TOPMed imputation server, a polygenic score for DCM (PGS DCM ; PGS000666) was calculated for cases and controls. The rate of (likely) pathogenic variants in known cardiomyopathy genes was reported in cases. Results/Data (descriptive and inferential statistics) The study included 107 cases and 878 controls. Case characteristics are shown in Table 1. The average PGS DCM for cases was significantly higher than that of controls (p-value <10 -10 ; Figure 1). Logistic regression with correction for age, sex, and ancestry (principal components) showed a strong association of PGS DCM with TAC (OR 1.99, 95% CI 1.54-2.58; p-value <10 -6 ). Notably, among patients with atrial tachyarrhythmias, those with a PGS DCM above the 95 th percentile had a 3.53-fold increased risk of TAC (p-value 4.5 -4 ). Exome sequencing in TAC cases identified only 2/107 (2%) carriers of (likely) pathogenic variants (in cardiomyopathy genes TNNT2 and MYH7 ). Conclusions Pathogenic variants account for a small minority of TAC cases. In contrast, a significant association between PGS DCM and TAC is suggestive of a shared polygenic pathway between TAC and DCM.

Abstract 4121348: Impairments in Left Atrioventricular Coupling Underpins Reductions in Skeletal Muscle Mass and Function in Ageing Older Adults

Background: Age-related cardiovascular disease (CVD) may manifest with changes in left ventricular (LV) systolic or left atrial (LA) dysfunction. Alterations in functional performance between the LV and LA chambers characterized by LA-LV coupling may be a sensitive marker representative of impairments in global cardiac performance, compared to either chamber alone. The increasing relevance of skeletal muscle function towards cardiac health in ageing, motivated our current work that investigated associations between skeletal muscle function and LA-LV coupling. Aim : Using advanced cardiac magnetic resonance (CMR) that characterizes cardiac volumetric parameters and strain functions, we determined the association between handgrip strength (HGS) and appendicular lean mass (ALM) with left atrioventricular coupling index (LACI). Methods: Community older adults without CVD underwent simultaneous assessment of HGS by hand dynamometer, height-square adjusted ALM by bio-impedance, and LA phasic function (namely reservoir, conduit, booster strain) as well as LA and LV volumetric parameters by CMR feature tracking. LACI is defined as the ratio of the ratio of LA to LV end-diastolic volumes. We performed linear regression and multivariable logistic regression to examine the relationship between HGS/ALM and LACI. Results: Among 251 study participants (mean age: 71 ± 9.1 years, female 44.7%), 149 (59%) had impaired LACI. HGS was linearly associated with LACI (β=-0.004, p=0.003) and LVEDV (β=1.62, p<0.0001), and ALM was linearly associated with LA volume (β=0.55, p=0.018) and LVEDV (β=3.45, p<0.0001) (Figure.1). Participants with impaired LACI (> 25%) had lower HGS (mean=22.8 ± 7.1 kg vs 26.1 ± 6.4 kg, p= 0.0002), lower ALM (16.4 ± 4.2 kg/m2 vs 17.7 ± 3.8 kg/m2, p=0.014), higher LA volume (36.8 ± 15.2 ml vs 22.0 ± 5.5 ml, p < 0.0001) and lower LV end-diastolic volume (101.0 ± 24.2 ml vs 111.9 ± 27.3 ml, p = 0.0011). The association between impaired LA-LV coupling and lower HGS (β=-0.0647, 95%CI -0.0255, -0.1040, p=0.001) and lower ALM (β=-0.0776, 95%CI -0.0107, -0.1444, p=0.011) persisted after adjusting for age. Conclusion: Reduced HGS and ALM among community-dwelling older adults was associated with impaired LA-LV coupling suggestive of underlying early-stage LA remodelling and impairments in left atrioventricular compliance. Detection of reduced HGS and ALM in community cohorts may prompt early identification of older adults at risk of dysfunctional cardiac aging.

Abstract 4144514: Human Immunodeficiency Virus Associated Cardiomyopathy- A Rare Cause of Heart Failure With Reduced Ejection Fraction in Era of Highly Active Antiretroviral Therapy

Introduction: Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era. Case Report: A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device. Discussion: Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

Abstract 4123630: MRPL44 Plays an Important Role in Cardiac Hypertrophy and Function

Background: Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. However, it remains unknown how MRPL44 contributes to cardiac function and hypertrophy. Aims: Our aim is to investigate the effect of MRPL44 haploinsufficiency in mice. Methods: MRPL44 haploinsufficient (MRPL44 +/- ) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44 +/- and wild-type (WT, MRPL44 +/+ ) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44 +/- and MRPL44 +/+ mice. Results: MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44 +/+ mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44 +/+ mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria. Conclusion: MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.

Abstract 4122035: The Distinct Natural History, Phenotype Spectrum, Familial Penetrance and Clinical Outcomes in Desmin ( DES )-Associated Cardiomyopathy

Background: Pathogenic/likely pathogenic variants (P/LP) in the desmin ( DES ) gene cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Research Questions: Limited data suggest that patients with P/LP DES variants have a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease requiring pacemaker implantation (CCD-PM), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, heart transplant, HF-related death). However, small cohort sizes have limited full clinical characterization. Aims: We aimed to describe the natural history, phenotype spectrum, familial penetrance and MACE in patients with P/LP DES variants identified via clinical genetic testing. Methods: We conducted a systematic review and individual patient data meta-analysis of cardiac and skeletal myopathy phenotypes and MACE (CCD-PM, VA and HF events) in patients with P/LP DES variants by retrieving publications from Medline (PubMed) and Embase. Diagnosis of cardiomyopathy or MACE were both considered evidence of cardiac involvement. Results: Out of 4,212 screened records, 72 met inclusion criteria. In total, 230 patients were included (52.6% male, 52.2% probands, median age: 31 years at first evaluation [22.0; 42.8]). Eighty-five (37.0%) patients showed isolated cardiac involvement, 89 (38.7%) cardiac and skeletal muscle involvement, 39 (17.0%) only skeletal muscle involvement, and 17 (7.4%) had neither phenotype. Overall, 130 (56.5%) patients were diagnosed with a cardiomyopathy and 134 (57.4%) patients developed MACE (96 [41.7%] had CCD-PM, 36 [15.7%] sustained VA, and 43 [18.7%] HF events). Familial cardiac disease penetrance was 69.1% (76/110) in relatives with P/LP DES variants. Out of 40 patients who presented with isolated CCD-PM phenotype, 18 (45.0%) were diagnosed with a cardiomyopathy after 6 [2.0; 16.0] years of follow-up. In multivariable analysis, male sex and non-missense variants were associated with higher risk of sustained VA (HR 2.71, p=0.008, and HR 4.62, p<0.001, respectively) and HF events (HR 2.63, p=0.005, and HR 2.79, p=0.015). Conclusions: DES cardiomyopathy demonstrates a distinct natural history, characterized by high familial penetrance and a high MACE burden. Male patients and those carrying non-missense variants are at higher risk for sustained VA events and may benefit from primary preventive ICD implantation even in the absence of severe LV systolic dysfunction.

Abstract 4134483: How succesfully can we presribe the 'four pillars' of medications for patients with heart failure with reduced LV systolic function?

Introduction: European, American and UK guidelines all endorse the prescription of the 'four pillars' of treatment (ACE/ARBs, b-blockers, MRAs and SGLT2 inhibitors) for heart failure with reduced LV systolic function (HFrEF). Many doctors believe that it is difficult to initiate and maintain patients on all these medications. We have studied 162 consecutive patients referred to our service as outpatients from primary care, subsequently diagnosed as having HFrEF, and our ability to establish them on these medications. Methods: Patients referred with potential heart failure (signs, symptoms and raised BNP) were identified as having HFrEF by echocardiography using British Society of Echocardiography (BSE) criteria. Patients attended regular outpatient appointments with a consultant cardiologist and specialist heart failure nurse and were prescribed and uptitrated all appropriate medications with any contraindications and intolerances noted. Results: Table 1 shows the number of patients sucessfully established on maximally tolerated doses of each class of medication. Reasons for not prescibing or discontinuing were: CKD 6, severe aortic stenosis 5, asthma 3, symptomatic bradycardia 5, hypotension 3, type1 diabetes 2, syncope 1, Raynauds 1, patient choice 8 and 6 patients died before all appropriate medications could be initiated. In 10 cases no clinical reason could be identified. It can be seen that a high proportion of patients were successfully established on each individual class of medication and more than two thirds of patients were able to be maintained on all four classes of therapy. Table 2 shows the breakdown of prescribing success according to the severity of LV dysfunction. It can be seen that prescribing success appears to be higher in those with the more severe LV dysfunction. Conclusions: 1. The majority of patients can be established and maintained on appropriate polypharmacy for the treatment of LV systolic dysfunction. 2. The severity of LV systolic dysfunction is not a negative predictor of success in prescribing.

New left ventricular thrombus and embolic events in left ventricular dysfunction postmyocardial infarction

Background: We aimed to assess the incidence and evolution of new left ventricular thrombus (LVT), and the incidence of manifest systemic embolism, in patients with severe left ventricular (LV) systolic dysfunction postacute anterior myocardial infarction (MI) who had been discharged on dual antiplatelet therapy. Methods: We prospectively included consecutive patients with postacute anterior MI and LV ejection fraction (LVEF) ≤35% or apical aneurysms or large infarctions with LVEF ≤40%. Transthoracic echocardiography (TTE) confirmed no LVT before hospital discharge, and a second TTE was performed at 30 days and a third one at 3 months. All TTE studies were prespecified to assess LVT, and the patients were screened for the development of clinically manifest systemic embolisms. Results: Two hundred and two consecutive patients (males 93%; mean age 55.2±6.4 years; mean LVEF 29.5±5.0%) were included. At 30 days (interquartile range: 2837 days), a new LVT was detected in 12 (5.9%) patients. Oral anticoagulant was added to all patients with LVT, and aspirin was continued in 5 (42.7%) patients for a month. The 3month TTE showed favorable evolution of LV size, LVEF and apical wall motion score index compared to the baseline. At 3 months, the LVT disappeared in 7 (58.3%) patients and 5 patients still had a mural LVT of smaller size, and none got new LVT. Among the group without LVT, one patient had a stroke, and another had a myocardial infarction and died. Conclusions: In contemporary practice, and using routine TTE, the incidence of new LVT in patients with severe LV dysfunction postacute anterior MI is low. They have a favorable LVT evolution with minor risk for clinically manifest systemic embolism.

Evaluation of subclinical LV systolic dysfunction by speckle tracking echocardiography in patients with Non-alcoholic fatty liver disease

Evaluation of subclinical LV systolic dysfunction by speckle tracking echocardiography in patients with Non-alcoholic fatty liver disease

Five-Year Outcomes with Self-expanding versus Balloon-expandable TAVI in Patients with Left Ventricular Systolic Dysfunction

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. We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve implantation (TAVI) with balloon-expandable vs. self-expanding THVs. In a retrospective analysis from the Bern TAVI registry, patients with LVEF <50% who underwent TAVI 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. 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 ≥mild-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%, HRadjusted: 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. 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. https://www. gov. NCT01368250.

Successful management of complete heart block in checkpoint inhibitor induced myocarditis by left bundle branch area pacing: a case report

Abstract Background Optimal management of checkpoint inhibitor-induced complete heart block is unknown. Previous reports showed relatively high incidence of pacing failure due to the co-existing myocarditis. Case summary A 71-year-old male with a prior history of stage IV metastatic squamous cell lung cancer presents was admitted for dyspnoea and hypotension 10 days after checkpoint inhibitor treatment using pembrolizumab. He was found to have myocarditis, third-degree AV block, severe left ventricular systolic dysfunction with EF 35%, and required pressure support. A dual chamber pacemaker using left bundle branch area pacing (LBBAP) was urgently placed that immediately improved his haemodynamics. Both the cathode and anode were able to capture the ventricle at different pacing outputs. The patient was taken off all intravenous pressors and successfully transferred to a larger centre for further management of the myocarditis with no further arrhythmia or hypotension. Discussion In conclusion, because of the unique ability to capture a large amount of myocardium from both the tip and ring electrodes as well as the ability to deliver cardiac resynchronization therapy, LBBAP may be the preferred pacing strategy in patients who develop complete heart block due to checkpoint inhibitor-induced myocarditis.

Common Echocardiographic Diagnoses in Patients at Tertiary Care Center: An Observational Study

Introduction: Echocardiography is an indispensable tool for the diagnosis and management of cardiac patients. It is important to know the spectrum of cardiac abnormalities detected by echocardiography for the proper management of patients. The aim of this study was to evaluate the echocardiographic diagnosis of patients at a multispecialty tertiary care hospital and find out the prevalence of various cardiac diseases diagnosed via echocardiography.Methods: This was a retrospective cross sectional study carried out at the Echocardiography lab of National Academy of Health Sciences. Records of all patients who had done Echocardiography from February 2024 to April 2024 were analyzed. Ethical approval was obtained from Institutional Review Committee (Reference Number:1231/2080/81).Results: Out of 3593 cases, there were 1750 (48.71%) female and 1843 (51.29%) male. Normal echocardiographic study was seen in 1184 (32.95%). Mean age was 56.13±17.38 years. Left ventricle diastolic dysfunction was seen among 1428 (39.74%), followed by tricuspid regurgitation 1026 (28.55%) and pulmonary hypertension 497 (13.83%). Other findings were, left ventricular hypertrophy 204 (5.67%), Left ventricular systolic dysfunction 165 (4.59%), rheumatic heart disease 102 (2.83%) and, congenital heart disease was the lowest documented finding, seen in 30 (0.83%).Conclusions: Most common diseases diagnosed by echocardiography in our study were, diastolic dysfunction, tricuspid regurgitation and pulmonary hypertension.

No Difference in Systolic Dysfunction from Left Ventricular Pressure-Volume Loop’s Area and Stroke Work Between Chronic Late Load vs. Early Systolic LV Load in Porcine Model

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;in increased LV afterload as in hypertension, early systolic LV dysfunction (SD) in late compares to early peak systolic LV load for P-V area, stroke work, potential energy with effective LV work (EW) is not being defined (aortic stenosis, arterial hypertension or coarctation of the aorta) in LVH remodeling. &amp;lt;i&amp;gt;Objectives:&amp;lt;/i&amp;gt; to assess in porcine model how LV stroke work, PVA and EW are related to LVH remodeling in developing early SD with HF, between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week in chronic LL compares to EL. It is suggested that reduced proximal thoracic or asc. aortic compliance results with myocardial ischemia. However, difference for LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand and effective LV work in different LV afterload is not understood in early development systolic HF. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; in fourteen domestic male pigs (28±3 kg) with moderate descending aortic banding having chronic late LV load (LL=8) or ascending aortic stenosis with early systolic LV load (EL=6) SD was assessed, from PVA, in invasive LV pressure-volume loops’ measurements, at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week, to assess LV maximal ESPVR, with Millar 5Fr P-V pig-tailed conductance catheter. LV stroke work, and pressure-volume area PVA, reflecting the maximal LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand were assessed in chronic LL compares to EL from nonlinear regression analysis of maximal LV end-systolic stiffness, in special software. For variance analysis, two-way repeated measures ANOVA was performed, with normality assessment. Results are means±(SEM) or medians for significant p&amp;lt;0.05. &amp;lt;i&amp;gt;Results: &amp;lt;/i&amp;gt;LV PVA was not different, in LL compared to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. LV stroke work with effective works were not different and potential energy, neither were changed between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. No difference was found in different LV afterload, in both indexed and absolute LVO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand, in LL vs. EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; or 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. Indexed PVA parameters with LV stroke work, effective work and potential energy were not different or changed in LL compares to EL between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; weeks, normalized per body surface-area (in m&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;). &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Both absolute and indexed LV stroke work, potential LV energy, PVA with EW and maximum LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand are not different in LL compares to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week of LVH remodeling, indicating no difference in early SD development in increased late vs. early LV afterload.

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&amp;lt;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 &amp;lt; 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 &amp;lt;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 &amp;lt;0.001) and a higher incidence of ³mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P &amp;lt;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 (&amp;lt;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&amp;lt;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&amp;lt;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 &amp;lt;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 &amp;lt;0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p &amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;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&amp;lt;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&amp;lt;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 &amp;lt;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 &amp;gt;40% then LVEF&amp;gt;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&amp;lt;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 &amp; 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 &amp;gt;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