Left Ventricular Myocardium Research Articles

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Automated DeepLabV3+ based model for left ventricle segmentation on short-axis late gadolinium enhancement-magnetic cardiac resonance imaging images

Accurate segmentation of myocardial scar tissue on late gadolinium enhancement-magnetic cardiac resonance imaging (LGE-CMR) is exceptionally vital for clinical applications, enabling precise diagnosis and effective treatment of various cardiac diseases, such as myocardial infarction and cardiomyopathies. However, the ventricle (LV) variations in the size and shape, artifacts, and image resolution of LGE-CMR has made automatic segmentation of myocardial scar tissue more challenging. While many existing approaches delineate the LV myocardium region using multi-modal segmentation, these models may be computationally complex and suffer from misalignment. Therefore, this study proposed an automatic dual-stage DeepLabV3+ based approach tailored for myocardial scar segmentation on short-axis LGE-MRI exclusively. To segment myocardial scar tissue, the second stage employs the segmented LV chamber from the previous stage. The encoder part of the framework utilizes a MobileNetV2 and ResNet50 backbone for the first and second segmentation, respectively, aiming for optimal resolution of feature maps. Both stages tailor an improved Atrous Spatial Pyramid Pooling module in the DeepLabV3+ model with fine-tuned dilated atrous rates to effectively extract the LV chamber and myocardial scar from the complex LGE-MRI background. Based on the results, the proposed dual-stage network recorded an outstanding segmentation performance, with mean Dice score of 96.02% for LV chamber segmentation and 68.01% for scar tissue extraction.

CARDIAC ULTRASOUND ALTERATIONS IN INDIVIDUALS WITH PNEUMONIA RELATED TO COVID-19 INFECTION

A wide range of cardiac effects are observed during the acute phase of COVID-19. Interestingly, troponin levels are raised in 8–28% of instances, while systolic myocardial dysfunction symptoms are not always evident. Subclinical myocardial dysfunction is more common and is commonly defined as a decrease in the left ventricle's global longitudinal strain (LV GLS). Up to 80% of individuals exhibit this alteration while they are in the hospital. LV GLS is a crucial component in risk assessment for follow-up care and a strong independent predictor of in-hospital mortality. The first results on the long-term cardiovascular effects of COVID-19 one year after hospitalization are presented in this study. One year after discharge, we found that patients with COVID-19 pneumonia had a negative trend in LV GLS and deformation metrics in the apical and certain middle segments of the LV myocardium, as compared to data collected three months after discharge. The purpose of the study is to look at the prevalence and clinical significance of long-term heart injury following COVID-19. In order to do this, we examined patient data and categorized patients a year following hospital discharge according to their LV GLS values. This method aids in comprehending the clinical ramifications of long-term cardiac injury after COVID-19.

Prognostic value of delayed gadolinium enhancement on cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy and an implanted cardioverter-defibrillator

Aim. To examine the impact of late gadolinium enhancement (LGE) in the left ventricular myocardium on magnetic resonance imaging (MRI) on overall mortality and the phases of arrhythmic events in patients with ischemic cardiomyopathy and implantable cardioverter defibrillator (ICD).Methods. This was a single-center retrospective study. A total of 382 medical records of patients from the period between 2019 and 2022, who underwent ICD implantation as part of primary prevention of sudden cardiac death at National Centre of Cardiovascular Surgery, were analyzed. Seventy-four patients were selected for the study. Observation was conducted through in-person examinations and remote monitoring. Endpoints evaluated included overall mortality and arrhythmic events. The cause of death was determined based on the “Promed” medical database. Patients who reached a specific endpoint constituted the case group, while those who did not reach any endpoint formed the control group.Results. During the observation period, arrhythmic events were registered in 26 patients (35.1%), with a total of 27.1±13.2 events. Twenty-one patients (28.4%) deceased. In univariate regression analysis, the presence of LGE, the extent of LGE (%), and the number of segments with LGE served as predictors of ICD activation and overall mortality. Two multivariate logistic regression models were constructed. ROC curves were used to determine the quality of the regression model, with an area under the curve of 0.807 for ICD activation and 0.789 for mortality. The highest sensitivity and specificity of the method were observed with a LGE value equal to or greater than 14% for ICD activation (sensitivity 81%, specificity 75%) and 26% for overall mortality (sensitivity 89%, specificity 64%).Conclusion. Substantiated ICD activations (shock/antitachycardia pacing) were observed in 35.1% of cases, and the overall mortality rate was 28.4%. The association between ICD activation and the extent of LGE occurred when LGE was >14%. The association between overall mortality and the extent of LGE occurred when LGE was >26%.

Poor in vivo transduction of myocardium by lentiviral vectors is likely caused by a post-entry block of transduction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Stichting LSH-TKI Introduction In cardiac gene therapy, two prototypic viral vectors are typically considered for long-term transgene expression, i.e. lentivirus (LV) and adeno-associated virus (AAV) vectors. Compared to AAV vectors, LV vectors have the advantages of a larger insert capacity and the ability to confer permanent transgene expression due to integration of the vector genome in the host cell’s chromosomal DNA . However, standard VSV G protein-pseudotyped LV vectors (VSV G-LV vectors) has shown suboptimal transduction of cardiac myocytes in vivo. Purpose In this study, we aimed to improve LV-mediated transduction of cardiomyocytes in vivo by evaluating LV vectors carrying various different envelopes and compared the most potent variants with AAV1 capsid-pseudotyped AAV2 vectors (AAV2/1 vectors). Methods We made a panel of LV vectors pseudotyped with envelope proteins from 76 different viruses carrying an expression cassette for enhanced green fluorescent protein (eGFP). Transduction efficiencies in neonatal rat ventricular myocytes (NRVMs), human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiomyocyte progenitor cells (CMPCs) were determined by fluorescence-activated cell sorting (FACS) as percentage eGFP-positive cells. Male NOD -SCID mice aged 3-6 months were injected directly into the left ventricular myocardium with eGFP-encoding VSV G-LV and AAV2/1 vectors at doses of 1.4 x 10^7 infectious units and 2.0 x 10^10 genome copies, respectively, or PBS as a control. Mice were sacrificed one and four weeks after surgery. Per heart, left ventricular and eGFP-positive area was determined from 40 – 50 slides and the ratio was used as a measure of transduction efficiency. Results Of the panel of pseudotyped LVs none was able to consistently outperform VSV G-LV vectors, which reached transduction efficiencies in vitro of 58% in NRVMs to 96% in hiPSC-CMs and 100% in CMPCs . In AAV2/1 vector-injected hearts, the eGFP expressing area in the left ventricle increased from 1.07% in week 1 to 5.42% in week 4. In contrast, eGFP expression in LV-injected hearts was 0.31% and 0.16% after 1 week and 4 weeks, respectively (figure 1). Conclusion In vitro screening of a panel of pseudotyped LV vectors showed standard VSV G-LV vectors as top performer. Despite encouraging in vitro results and previously reported findings, VSV G-LV vectors was unable to provide for robust in vivo transduction. The observation that none of the 76 different envelopes yielded a meaningful improvement of lentiviral transduction rates together with the discrepancy between in vitro and in vivo transduction efficiencies, suggest that a post-entry block of transduction likely represents an important component of the poor in vivo performance.Figure 1in vivo transduction

The diabetic myocardial transcriptome reveals Erbb3 as a novel biomarker of incident heart failure

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation Background/Introduction People with diabetes mellitus (DM) are at high risk of developing heart failure, but the molecular basis of this is not well understood. Elucidating the mechanistic pathways may help to improve patient stratification and develop targeted therapies. Purpose We set out to define differentially expressed genes (DEGs) in diabetic myocardium and validate arising hits in their circulating protein form, with a view to informing biomarker development and improving understanding of diabetic heart disease. Methods Transcriptomic (RNA-seq) data from the Genotype-Tissue Expression (GTEx) project was used to compare gene expression in participants with (n=>100) versus without (n>300) DM (pooled type 1 and 2 diabetes mellitus), in both the right atrial (RA) and left ventricular (LV) myocardium; analyses were adjusted for technical, demographic and disease covariates. Where available, plasma proteomic data from the UK Biobank (UKB) cohort was used to validate DEGs from GTEx in their circulating protein form. Hits with directionally concordant differential expression in GTEx and UKB were further characterised as plasma proteins in UKB, including over 50,000 participants irrespective of DM status; this included analysis of incident heart failure, cardiovascular mortality and left ventricular function on cardiac magnetic resonance imaging. Results Pooled across the RA and LV, there were 64 DEGs associated with DM, with no overlap between the RA and LV hits. UKB plasma protein data was available for 6 of these. Only ERBB3 showed directional concordance with transcriptomic data, being lower in the myocardium and blood of people with DM. People in the lowest quartile of ERBB3 plasma protein had increased adjusted risk of incident heart failure and cardiovascular death than participants in all other quartiles. Lower concentrations of plasma ERBB3 protein were also associated with increased LV mass and impaired LV contractility. Conclusion Lower plasma ERBB3 concentration is more common in people with DM and is associated with LV dysfunction, incident heart failure and cardiovascular mortality. This highlights the potential of ERBB3 as a novel biomarker for individuals at risk of heart failure. Importantly, cancer therapies targeting ERBB3 and related family members can induce heart failure, and recombinant forms of the ERBB3 ligand neuregulin-1 appear to improve LV contractility, further suggesting a role of ERBB3 in the development of diabetic heart disease.

Volume-weighted unipolar voltage identifies diffuse fibrosis in patients with non-ischemic cardiomyopathy

Abstract Background Late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMR) is currently used to identify non-ischemic scar. However, the distribution of non-ischemic fibrosis related to ventricular arrhythmia (VA) may vary between patients and cannot be accurately delineated by LGE-CMR. Myocardial extracellular volume fraction (ECV) is a promising tool to estimate the amount of diffuse fibrosis in non-ischemic cardiomyopathies (NICM). Novel intra-cardiac mapping derived tools, such as volume-weighted unipolar voltage (vwUV), may allow intraprocedural quantification of diffuse fibrosis. Purpose To evaluate the performance of vwUV to determine the segmental amount of non-ischemic fibrosis defined by whole-heart T1 mapping. Methods Consecutive patients with a left dominant NICM referred for ablation of VA, who underwent 3D LGE-CMR, whole-heart pre- and post-contrast T1 mapping and high density electroanatomical voltage mapping (EAVM) were included. CMR images were segmented and merged with the 3D EAVM data. The 16-segment AHA model was applied and vwUV and ECVs were determined per segment. Results Twenty-one patients (age 54 years [49-60], 18 males [87%], LVEF 47% [37-57%], LGE 7.7% (2.8-18.2%) of LV myocardium) were included and 305 segments analysed. The median ECV per patient was 30.3% (28.8-35.2%). The median segmental vwUV was 1.8mV (1.2-2.3mV). The basal septal and basal inferolateral segments tended to have higher ECV. However there was important variation between patients (figure 1). Of note, the segmental vwUV correlated well with segmental ECV (r = -0.53, p < 0.001) (figure 2). Conclusions For the first time, a segmental comparison has been performed between ECV and vwUV. There are important segmental variations of ECV between patients with a NICM referred for VA ablation. The novel intra-cardiac mapping-derived tool of vwUV can localize non-ischemic fibrosis and may facilitate substrate based ablation approaches in this challenging patient population.Figure 1.Segmental ECV valuesFigure 2.Segmental ECV and vwUV

#951 Structural and functional indicators of the left heart in the aspect of contrast-induced nephropathy

Abstract Background and Aims To study the structural and functional features of the left heart in patients with coronary artery disease depending on the development of contrast-induced nephropathy (CIN) against the background of radiopaque endovascular procedures (REP). Method The study included 303 patients with stable forms of coronary artery disease who underwent X-ray endovascular procedures (REP). Patients with eGFR, determined by serum creatinine concentration, less than 60 ml/minute were not included in the study. 20 healthy volunteers were examined as a control group. All patients were divided into 2 groups - patients with an uncomplicated postoperative period of REP (CIN- group, 206 patients, 67.99%) and patients who developed contrast-induced nephropathy (CIN+ group, 97 patients, 32.01%). Subsequently, the CIN+ and CIN- groups were retrospectively compared based on baseline echocardiographic parameters. Results The present study demonstrated that EchoCG predictors of CIN in patients with stable forms of coronary artery disease are dilatation of the left ventricular (LV) cavity more than 136 ml (relative risk 1.65, p < 0.01), an increase in the index of impaired regional contractility of the LV to 1.2 points or higher (relative risk 1.77, p < 0.01) and a decrease in the e/a ratio of tissue Dopplerogram of the lateral edge of the mitral annulus to 0.7 relative units or less (relative risk 1.59, p < 0.01). Conclusion In patients with coronary artery disease after REP, despite the improvement in the index of impaired regional contractility and the index of LV sphericity, in the CIN+ group there is a more significant deterioration in the structural and functional properties of the LV myocardium, which manifested itself in an increase in systolic myocardial stress, a decrease in ejection fraction and an increase in the degree of diastolic dysfunction, which indicates a toxic effect of the radiocontrast drug not only on the kidneys, but also on the myocardium.

“A BROKEN TRANSPLANTED HEART”: A CASE OF TAKOTSUBO SYNDROME IN A HEART TRANSPLANT RECIPIENT

Abstract 75–year–old female patient went to the emergency department for oppressive chest pain radiating to the left arm and dyspnea, developed after an argument with family members. The patient underwent heart transplant in 2010 because of chronic ischemic heart disease. In history: systemic arterial hypertension, former smoking, dyslipidemia, and chronic renal failure. At blood tests: TnIHS 78.4 ng/L (<29 ng/L), CK–MB 1.9 microg/L, PROBNP–NT 43,000 pg/ml, creatinine 2 mg/dL. ECG showed inverted T waves in DI, AVL and V4 to V6 (fig 1). Transthoracic echocardiography was remarkable for a moderate reduction in systolic function (EF 38%), akinesia of apical portion, mid–segment of the IVS and mid–segment of posterior wall. Coronarography showed epicardial coronaries free of angiographically significant lesions. We decided to not perform ventriculography to avoid worsening renal function. At clinical stabilization, the patient underwent cardiac MRI with evidence of hypokinesia of the mid–ventricular segments with preserved global systolic function and hypo/akinesia of right ventricular apex with endocavitary thrombosis. Tissue characterization images were compatible with the presence of diffuse phlogistic involvement of the left ventricular myocardium (most evident at the mid–ventricular segments), in the absence of areas of myocardial necrosis. On pre–dimission echocardiogram, global left ventricular systolic function appeared markedly improved (auto EF 52%). DISCUSSION Our case is a rare case of Takotsubo syndrome (TS) in a transplanted heart. While TS accounts for 1–2% of all ACS in the general population, there is no precise data on its prevalence in heart transplant recipients. Although the pathophysiological mechanism underlying TS is still debated, there is evidence of hyperactivation of the sympathetic system with excessive catecholamine release. What is particular in our clinical case is that transplanted heart is denervated (because of resection of the post–ganglionic neural axons), although in some patients there is progressive reinnervation starting around the second year. Myocardial scintigraphy with iodine–123 meta iodobenzylguanidine can be used to study reinnervation. In our case, the presence of typical angor may be a clinical indicator of reinnervation, as many transplant patients present with CAV in the absence of chest pain.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.

Four-dimensional computed tomography is useful for detection of apical sparing of cardiac amyloidosis.

A 73-year-old male was admitted because of recurrent syncope. He was diagnosed with transient bradycardia caused by a 2:1 atrioventricular block, and he underwent cardiac computed tomography (CT) using 320 detector-row CT to screen for coronary artery disease. Significant coronary artery stenosis was not detected, but diffuse late iodinate enhancement was found on the epi-myocardium and endo-myocardium of the interventricular septum, and endo-myocardium of the anterior and lateral left ventricular (LV) myocardium (LVM) on CT. The ejection fraction and global longitudinal strain (LS) of LVM were 53.97% and - 9.87% on CT. Apical sparing was present, meaning the LS of LV apical segments were preserved compared with basal segments on CT. Pathological findings of LVM demonstrated loss of myocardial cells and extra-cellular amyloid deposition on the direct fast scarlet staining. He was finally diagnosed with transthyretin amyloidosis.

Mitral annular disjunction and its progression during childhood in Marfan syndrome.

Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI -0.0002, +0.0005 mm/m/year). MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS.

Remodelling and functional features of the left ventricle in miners

Introduction. Diseases of the circulatory system are the main cause of mortality in the employable population. Preserving occupational longevity involves the identification of early signs of myocardial damage by modern techniques, which will allow taking a fresh look at the prevention of cardiovascular pathology in people engaged in harmful working conditions. Materials and methods. The study included two hundred thirty six miners of average age of 47.1±0.36 years who underwent periodic medical examination at the Institute clinic. The work experience in hazardous occupation conditions was 22.7±0.6 years. The study was based on transthoracic echocardiography using tissue Dopplerography and speckle tracking technology. Results. Concentric remodelling of the left ventricle was detected in 25.9% of the miners. Arterial hypertension was revealed in 65.6% of the miners with concentric remodelling of the left ventricle versus 34.3% of the miners with its normal geometry (p=0.00002). There were no significant differences in the left ventricular contractile function indices in the groups. In both groups, diastolic dysfunction type 1 was predominantly detected, which was significantly more common in the miners with concentric remodelling of the left ventricle (62.3% and 42.0%, p=0.006). Pseudonormal type of diastolic dysfunction occurred in 8.2% of the group with concentric remodelling versus 5.14% with normal left ventricular geometry, p= 0.38. Limitations. The study was limited by the number of the examined persons undergoing periodic medical examination at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. Conclusion. Remodelling of the left ventricular myocardium in miners did not correlate with a decrease in the longitudinal deformation of the left ventricle, which indicates the possible influence of harmful occupational factors on the development of its systolic dysfunction. Diastolic dysfunction of the left ventricle had a clear relationship with remodelling of the left ventricular myocardium. In this regard, it is recommended to conduct echocardiography during an in-depth periodic medical examination of miners with long-term work experience to identify a risk group for developing cardiovascular accidents.

“Interstitial fibrosis is associated with left atrial remodeling and adverse clinical outcomes in selected low-risk patients with hypertrophic cardiomyopathy”

BackgroundCardiovascular magnetic resonance (CMR) extracellular volume (ECV) allows non-invasive detection of myocardial interstitial fibrosis, which may be related to diastolic dysfunction and left atrial (LA) remodeling in hypertrophic cardiomyopathy (HCM). While the prognostic role of LGE is well-established, interstitial fibrosis and LA dysfunction are emerging novel markers in HCM. This study aimed to explore the interaction between interstitial fibrosis by ECV, LA morpho-functional parameters and adverse clinical outcomes in selected low-risk patients with HCM. Methods115 HCM patients and 61 matched controls underwent CMR to identify: i) interstitial fibrosis by ECV in hypertrophied left ventricular LGE-negative remote myocardium (r-ECV); ii) LA indexed maximum (LAVi max) and minimum (LAVi min) volumes, ejection fraction (LA-EF) and strain (reservoir εs, conduit εe and booster εa), by CMR feature-tracking. 2D-echocardiographic assessment of diastolic function was also performed within 6 months from CMR. A composite endpoint including worsening NYHA class, heart failure hospitalization, atrial fibrillation and all-cause death was evaluated at 2.3 years follow-up. HCM patients were divided into two groups, according to r-ECV values of controls. ResultsPatients with r-ECV ≥29% (n = 45) showed larger LA volumes (LAVimax 63 vs. 54 ml/m2, p < 0.001; LAVimin 43 vs. 28 ml/m2, p 〈0001), worse LA function (εs 16 vs. 28%, εe 8 vs. 15%, εa 8 vs. 14%, LA-EF 33 vs. 49%, all p < 0.001) and elevated Nt-proBNP (1115 vs. 382 pg/ml, p = 0.002). LA functional parameters inversely correlated with r-ECV (εs r = −0.54; LA-EF r = −0.46; all p < 0.001) and E/e' (εs r = −0.52, LA-EF r = −0.46; all p < 0.006). r-ECV ≥29% and LAVi min >30 ml/m2 have been identified as possible independent factors associated with the endpoint. ConclusionsIn HCM diffuse interstitial fibrosis detected by increased r-ECV is associated with LA remodeling and emerged as a potential independent predictor of adverse clinical outcomes, on top of the well-known prognostic impact of LGE.

Performance of the left ventricular myocardium in patients with a negative test result during exercise stress echocardiography

Aim. To determine the possibility of identifying patients with significant coronary artery disease (CAD) by evaluation of the left ventricular (LV) myocardial work indicators by constructing pressure-strain loops despite a negative test result during exercise stress echocardiography. Materials and methods. The study included 79 patients with suspected or previously confirmed CAD, of which 47 (59%) men, who had a negative test result during exercise stress echocardiography on the treadmill. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were evaluated using the technique of constructing pressure-strain loops at rest and at peak exercise. Results. With similar systolic blood pressure and LV ejection fraction at peak exercise between the control group and the group of patients with single-vessel CAD, there was revealed significant difference in GWI, GCW and GWE at peak exercise. In patients with multi-vessel CAD, GWI and GCW also significantly differed from the control group at peak exercise. Conclusion. The evaluation of LV myocardial work indicators may be recommended for a more accurate diagnosis of CAD in negative or unreliable test results during exercise stress echocardiography.

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart disease in the patients taking GBP. Given GBP can bind with high affnity to the α2δ subunits of voltage-gated Ca2+ channels (VGCCs) to block Ca2+ influx of cardiomyocytes, we hypothesize GBP suppresses cardiac function by evoking calcium signaling dysfunction. By using a preclinical rat model treated with GBP, we investigated (1) the acute cardiovascular responses to GBP (bolus i.v. injection; 50 mg/kg, 100 mg/ml x 0.1 ml in 3 min) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane-anesthesia, blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics of the rats were measured using two Millar pressure transducers; one was implanted in abdominal aorta via right femoral artery, and the another was implanted in the LV chamber via right carotid artery. The LV myocardium was analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction, with the brain cortex used as a control tissue. In experiment (1), we found that i.v. GBP treatment significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (*p &lt; 0.05 and **p &lt; 0.01 vs baseline; n = 4/group). This cardiovascular inhibition started at the injection time point and lasted at least 60 min, with a maximal effect appearing at 30 min post injection. In experiment (2), we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium of these rats, we used mass spectra to identify 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Particularly, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain, suggesting a myocardium-specific dysregulation of calcium signaling pathway, which may play a critical role in GBP-induced cardiac inhibition. Subsequent bioinformatics assays revealed a reduced Ca2+ release of sarcoplasmic reticulum (SR) and increased electrophoretic Ca2+ uptake into the matrix of mitochondria in the hearts of GBP-treated rats. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes where GBP binds to VGCCs to reduce extracellular Ca2+ influx and cytosolic Ca2+ release from SR, resulting in blockage of excitation-contraction coupling. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function. This project is funded by NIH R01 HL 160820. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

FEATURES OF MYOCARDIAL DEFORMATION PROPERTIES IN RELATION TO LEFT VENTRICULAR REMODELING TYPES IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: to determine the features of myocardial deformation properties in relation to left ventricular (LV) remodeling types in patients with arterial hypertension (AH). Design and method: The study included 62 patients of both sexes, with I–III degrees AH (ESC/ESH, 2018), who are undergoing outpatient treatment at the Republican Specialized Scientific and Practical Medical Center of Cardiology. The average age of patients was 53.1 ± 11.3 years, and the average duration of AH was 6.7 ± 6.5 years. Speckle-tracking EchoCG was performed to obtain an objective and quantitative assessment of global and regional myocardial function using SIEMENS's ACUSON x700 PV 2.0 system. Deformation properties of the LV myocardium were analyzed using the TOMTEC-ARENA Software system (TTA2.40.00). Among parameters for assessing longitudinal deformation of the LV we selected: global longitudinal strain -GLS (%); Strain Rate-SR (s-1). To study the segmental LV contractility, we analyzed the apical 4-chamber, 3-chamber, and 2-chamber section, the LV section along the short axis at the level of the mitral valve cusps, papillary muscles, and apex. Results are presented as M±SD. Results: The examined patient sample revealed three groups of LV geometric models: group I, n=27 (45.3%) patients with normal geometry; group II, n=27 (45.3%) patients with concentric remodeling; group III, n=8 (12.9%) patients with concentric hypertrophy. The absolute GLS values of the LV were: in group I - 20.0 ± 2.95%, in group II - 15.2 ± 2.99%, and in group III - 13.5 ± 1.87%. Inter-group analysis revealed that in the group with normal geometry, myocardial deformation properties of the LV were not impaired compared to II and III groups, as indicated by the GLS value within the normal range in group I patients (p &lt; 0.001). The lowest values of LV deformation were found in the group with concentric geometry, possibly influenced by factors such as the degree of hypertrophy, the presence of fibrosis in the myocardium, and diastolic dysfunction of the LV. Conclusions: Thus, in patients with AH and the presence of concentric hypertrophy, significant impairments in myocardial deformation properties of the LV are formed.

Arrhythmia onsets triggered by acute myocardial ischemia are not mediated by lysophosphoglycerides accumulation in ventricular myocardium

Lysophosphoglycerides (LPLs) have been reported to accumulate in myocardium and serve as a cause of arrhythmias in acute myocardial ischemia. However, in this study we found that LPLs level in the ventricular myocardium was decreased by the onset of acute myocardial ischemia in vivo in rats. Decreasing of LPLs level in left ventricular myocardium, but not right, was observed within 26 min of left myocardial ischemia, regardless of whether arrhythmias were triggered. Lower LPLs level in the ventricular myocardium was also observed in aconitine-simulated ventricular fibrillation (P < 0.0001) and ouabain-simulated III° atrioventricular block (P < 0.0001). Shot-lasting electric shock, e.g., ≤ 40 s, decreased LPLs level, while long-lasting, e.g., 5 min, increased it (fold change = 2.27, P = 0.0008). LPLs accumulation was observed in long-lasting myocardial ischemia, e.g., 4 h (fold change = 1.20, P = 0.0012), when caspase3 activity was elevated (P = 0.0012), indicating increased cell death, but not coincided with higher frequent arrhythmias. In postmortem human ventricular myocardium, differences of LPLs level in left ventricular myocardium was not observed among coronary artery disease- and other heart diseases-caused sudden death and non-heart disease caused death. LPLs level manifested a remarkable increasing from postmortem 12 h on in rats, thus abolishing the potential for serving as biomarkers of sudden cardiac death. Token together, in this study we found that LPLs in ventricular myocardium were initially decreased by the onset of ischemia, LPLs accumulation do not confer arrhythmogenesis during acute myocardial ischemia. It is necessary to reassess the roles of LPLs in myocardial infarction.

Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy

Aging induces cardiac remodeling, resulting in an increase in the risk of suffering heart diseases, including heart failure. Collagen deposition increases with age and, together with sarcomeric changes in cardiomyocytes, may lead to ventricular stiffness. Multiphoton (MP) microscopy is a useful technique to visualize and detect variations in cardiac structures in a label free fashion. Here, we propose a method based on MP imaging (both two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) modalities) to explore and objectively quantify age-related structural differences in various components of cardiac tissues. Results in transmural porcine left ventricle (LV) sections reveal significant differences when comparing samples from young and old animals. Collagen and myosin SHG signals in old specimens are respectively 3.8x and &gt;6-fold larger than in young ones. Differences in TPEF signals from cardiomyocyte were ∼3x. Moreover, the increased amount of collagen in old specimens results in a more organized pattern when compared to young LV tissues. Since changes in collagen and myosin are associated with cardiac dysfunction, the technique used herein might be a useful tool to accurately predict and measure changes associated with age-related myocardium fibrosis, tissue remodeling and sarcomeric alterations, with potential implications in preventing heart disease.

Relationship between left ventricular mechanical dyssynchrony and accelerated 99mTc-MIBI clearance in patients with heart failure

Aim. To evaluate 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) washout rate and its relationship with contractility and left ventricular (LV) mechanical dyssynchrony in patients with heart failure (HF) of non-ischemic origin.Material and methods. The study included 20 patients with HF of non-ischemic origin with indications for cardiac resynchronization therapy (CRT). Ten patients without HF were included in the comparison group. All patients underwent 99mTc-MIBI myocardial perfusion scintigraphy (MPS). We assessed the 99mTc-MIBI washout rate, as well as LV perfusion, contractility, and mechanical dyssynchrony using phase analysis data (phase standard deviation, histogram bandwidth (HBW), asymmetry, and gradient). Six months after CRT, all patients with HF underwent MPS to assess the changes of studied parameters.Results. According to MPS, patients with HF had a higher 99mTc-MIBI washout rate from the LV myocardium compared with the comparison group (10,9 (8,49-13,8) vs 3,98 (0,9-9,8)%, p=0,0001), as well as severe LV mechanical dyssynchrony (standard deviation: 66 (55,11-73,24) vs 13,1 (10,1-19,6), p&lt;0,0001; HBW: 207 (165-246) vs 40 (33-66), p&lt;0,0001). The 99mTc-MIBI washout rate was positively correlated with LV end-diastolic (r=0,46, p&lt;0,001) and LV end-systolic volumes (r=0,44, p&lt;0,001) and negatively correlated with LV ejection fraction (r=0,41, p&lt;0,001). A moderate correlation was found between the 99mTc-MIBI washout rate and following LV mechanical dyssynchrony and contractility parameters: HBW (r=0,412, p&lt;0,001), asymmetry (r=-0,41, p&lt;0,001), gradient (r=-0,44, p&lt;0,001), wall motion (r=-0,45, p=0,001), wall thickening (r=-0,54, p&lt;0,001). Six months after CRT, all patients showed a significant decrease in the 99mTc-MIBI washout rate from 12,4 (10,3-14,9) to 8,14 (3,37-8,88)%, p=0,0006.Conclusion. In patients with HF of non-ischemic origin, an increase in the 99mTc-MIBI washout rate from the LV myocardium is associated with the severity of impaired cardiac contractility and mechanical dyssynchrony.