Systolic Performance Research Articles

Rats with Postinfarction Heart Failure: Effects of Propranolol Therapy on Intracellular Calcium Regulation and Left Ventricular Function

Patients with heart failure may live longer if they receive chronic treatment with beta-adrenergic blocking medications. Unresolved are the mechanisms underlying the beneficial effects and if they may be applied to ischemic heart failure. Rats (n = 28) underwent echocardiographic-Doppler exams one and six weeks following a simulated operation or myocardial infarction (MI). After the first echocardiography, rats were randomized to either no therapy or 500 mg/l of propranolol in their drinking water. The noninfected left ventricular (LV) papillary muscles were used to record isometric contractions and intracellular Ca transients simultaneously. Untreated MI rats had a restrictive LV diastolic filling pattern, decreased systolic function (13% ± 2%), and significant LV dilatation (10.6 ± 0.4 mm vs. 8.9 ± 0.3 mm, MI vs. control). The LV chamber diameters of the propranolol-treated MI rats were 10.6 ± 0.5 mm, and systolic performance (13% ± 2%). Higher LV end-diastolic pressures (27 ± 2 mmHg vs. 20 ± 3 mmHg) and a more constrained LV diastolic filling pattern (increased ratio of early to late filling velocities and faster E wave deceleration rate) were seen in the propranolol-treated animals. Papillary muscle contractility in untreated MI rats was lower (1.6 ± 0.3 g mm²). Furthermore, the inotropic response to isoproterenol was attenuated, and Ca transients were extended. During isoproterenol stimulation, beta-adrenergic blocking administration had no effect on force development (1.6 ± 0.3 g mm²) or the length of Ca transients. Rats with postinfarction heart failure receiving chronic propranolol treatment did not have improvements in systolic function or LV remodeling. Propranolol exacerbated LV diastolic pressures and filling patterns. Additionally, there was no discernible improvement in intracellular contractility following treatment, Calcium control, or beta-adrenergic sensitivity in the myocardium that is not infarcted).

Left ventricular systolic performance in adults after arterial switch operation. Echocardiographic data from EPOCH-ASO: a multi-centric international registry

Abstract Background The arterial switch operation (ASO) is the current technique of choice for the repair of the transposition of the great arteries (d-TGA). Its main advantage is that the left ventricle (LV) sustains the systemic circulation, thus diminishing the risk of late systolic dysfunction as seen in the atrial switch technique. Purpose To study the systolic LV performance in a large cohort of adult patients after ASO and to explore clinical determinants of reduced left ventricular systolic function (LVSF). Methods EPOCH-ASO is an ongoing prospective, multicentre, international cohort study involving 11 reference centres from 5 different countries, that includes adult d-TGA patients after ASO. We conducted a cross-sectional analysis of clinical and echocardiographic data from all patients enrolled in EPOCH-ASO. LVSF was considered reduced when ejection fraction (EF) by Simpson’s method was < 54% in women or <52% in men, or by visual assessment when EF could not be obtained. Results 513 patients have been included in EPOCH-ASO, with a median age of 25.3 years [IQR: 21 – 28 years] at the time of enrolment. At baseline, 41% had history of at least one reintervention (23.2% at the right ventricular outflow tract (RVOT), 5.1% at the left ventricular outflow tract (LVOT), 4.5% at the aortic arch, 3.3% pacemaker implantation). Echocardiographic data were obtained in 450 patients (88 % of the total cohort). Left ventricular ejection fraction (LVEF) by biplane Simpson method was available in 316 patients (mean LVEF 58.3 ± 7.2%), while visual assessment of LVSF was performed in 134 patients. For the total cohort with echocardiographic data available, 62 (13.8%) had a reduced LVSF. Global longitudinal strain (GLS) analysis was available in 145 patients (28.2% of the total cohort), with a mean value of -17.4% ±2.7%. GLS was impaired (>-18%) in 53% of the patients. Furthermore, 48% of the 117 patients with normal LVEF had a reduced GLS. Older age at the time of the echocardiography, late repair (>12th day), a previous pulmonary banding or having a pacemaker implanted were factors associated with an impaired LVSF. In the multivariate analysis, age at the time of the echocardiography (OR 1.06 per year, CI 1.01-1.12; p<0.001) and late repair (OR 1.85, CI 1.11-3.06, p=0.03) remained significant. As for the speckle tracking analysis, a significantly lower GLS was found in patients after LVOT intervention (-15% vs -17.6%, p=0.005) and with a neo-aortic root above the median (37.5 mm) (GLS -17% vs -18%, p=0.03). In the multivariate analysis only LVOT intervention remained significant (p=0.016). Conclusions Left ventricular systolic dysfunction is not exceptional in patients after ASO and it may become a concern as this population ages. Speckle tracking analysis might identify earlier stages of ventricular dysfunction. Large comprehensive longitudinal studies are needed to better characterize the left ventricular systolic function in this patient population.

Combined myocardial performance index as an echocardiographic predictor of prognosis in acute ST-elevation myocardial infarction

Abstract Background Myocardial infarction induces variable degrees of impairment in left ventricular (LV) systolic and diastolic functions. Right ventricular (RV) dysfunction can occasionally coexist with LV dysfunction. The most popular techniques for assessing systolic and diastolic function, respectively, the ejection fraction (EF) and transmitral flow, both have significant limitations. The myocardial performance index (MPI) is a single parameter that does not have these restrictions and can estimate both combined systolic and diastolic performance. We used the combined myocardial performance index (CMPI) (LV MPI + RV MPI) as a new predictor of prognosis in patients with ST-elevation myocardial infarction (STEMI). Objectives The purpose of this study was to evaluate the CMPI as an echocardiographic prognostic indicator in STEMI patients. Methods 200 STEMI patients who underwent primary PCI were enrolled. Echocardiography was done within 24 h of clinical signs with measurement of LV MPI and RV MPI. The MPI was calculated as (isovolumic contraction time + relaxation time)/ejection time. The one-year cardiovascular mortality rate from the time of admission was selected as a prognostic indicator. Results The one-year cardiovascular mortality rate was 9% (18 patients). LV MPI was found to have a significant positive correlation with the development of 1-year death (p = 0.036), while CMPI was found to have a highly significant positive correlation (p = 0.0001). A cut-off point of MPI > 0.50 showed 65.9% specificity and 94.4% sensitivity for the prediction of one-year death (Area-0.659). On the other hand, a cut-off point of CMPI > 0.92 has shown 94.4% sensitivity and 95.1% specificity for identifying patients with a one-year death risk (Area - 0891). Conclusions The CMPI might be a strong prognostic predictor after acute STEMI.LVMPICMPI

Speckle tracking echocardiography detects subtle right ventricular systolic dysfunction in post Covid syndrome after mild severity Covid-19

Abstract Introduction Now that the global COVID-19 pandemic has come to an end, many patients seek medical help for its aftermath giving rise to post COVID syndrome. Post COVID syndrome describes individuals with a history of probable or confirmed COVID-19 infection, usually 3 months from the onset of infection with symptoms that last for at least 2 months and no alternative diagnosis can be explained. The affection of the right ventricular (RV) systolic function is a cornerstone in the pathogenesis underlying Post COVID syndrome. Many modalities were used to assess the RV with a widespread debate as to the most accurate one. However, echocardiography remains the modality of choice for the evaluation of RV systolic function, especially when using its novel features as myocardial deformation imaging by speckle tracking echocardiography (STE) to surpass the RV’s peculiar anatomy, retrosternal position and complex architecture. Purpose The aim was to assess RV systolic function by STE 3-6 months after recovery from mild severity COVID-19 disease and correlate these findings with Post COVID syndrome. Methods This study included 96 adults (above 18 years of age) who were classified into three equal groups; the first group recruited 32 subjects 3-6 months after recovery from mild severity COVID-19 disease without post COVID syndrome, the second group included 32 subjects 3-6 months after recovery from mild severity COVID-19 disease with post COVID syndrome and the third group recruited 32 gender-matched healthy subjects of similar ages without previous COVID-19 disease (control group). Each subject underwent a detailed transthoracic echocardiography including RV function assessment using 2D RV STE imaging. Results RV global longitudinal strain (GLS) and RV free wall longitudinal strain (FWLS) were significantly lower in patients after recovery from mild severity COVID-19 disease with post COVID syndrome (P-value= 0.010) in comparison to the other groups. There was a statistically significant negative correlation found between RV 2D STE parameters and RV end-diastolic dimension, systolic pulmonary artery pressure and RV myocardial performance index. Also, there was a statistically significant positive correlation found between RV 2D STE parameters and RV fractional area change, tricuspid annular plane systolic excursion and RV S'. The cardiac symptomatology in patients with post COVID syndrome was analyzed showing that the most common three symptoms were fatigue, palpitations and chest pain with a prevalence of 65.6%, 40.6% and 31% respectively. These three symptoms showed a significant negative relation with RV-GLS and RV-FWLS. Conclusion RV function assessed using STE occupied the lower normal ranges in patients recovering from mild severity COVID-19 disease, particularly those with post COVID syndrome. 2D STE may be used for the detection and follow-up of possible subtle long term RV dysfunction after mild severity COVID-19 disease.RV-GLS and RV-FWLS in the studied groupsRV-GLS and RV-FWLS using 2D STE

Structural and functional abnormalities of cardiac chambers in Barlow disease without significant mitral regurgitation

Abstract Background Limited and conflicting data have been reported on the existence of an early chamber remodelling in patients with Barlow disease (BD) without significant mitral regurgitation (MR). Purpose To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities, evaluated by conventional and speckle-tracking echocardiography, in patients with BD and without significant MR; in addition, potential determinants of MR progression in these patients have been investigated. Methods We retrospectively identified consecutive patients with BD evaluated in two tertiary centers between 2010 and 2021. Only patients with MR graded from trivial to mild-to-moderate, as defined by an integrated multiparametric echocardiographic assessment, were selected. BD patients were matched with healthy controls with similar demographic characteristics and prevalence of cardiovascular risk factors, in a 1:1 ratio. A comprehensive echocardiographic evaluation, including LV and LA strain assessment by speckle-tracking analysis, was performed in all patients. Follow-up echocardiograms, when available, were reviewed in BD patients to evaluate the MR progression. Results A total of 231 patients with BD were included, of which 109 (56%) had trivial or mild MR and the remaining 122 (44%) had mild-to-moderate MR. As showed in Figure 1, patients with BD showed increased LV dimensions and indexed LV mass (LVMi), as compared with controls (all p<0.001); LV remodelling worsened with higher degree of MR (trivial-mild vs mild-to-moderate) and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Conversely, parameters of LV systolic performance, including LV strain, were similar to controls and between the two groups. In addition, BD patients had larger LA volumes and more impaired LA reservoir strain than controls (p<0.001), without differences in the latter according to MR severity. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi and LA volumes), and BD as independent correlate of LA reservoir strain. Progression to moderate-to-severe or greater MR was observed in 51 subjects (on 172 with available follow-up) after a median time of 38 (range: 24-68) months. On multivariable Cox regression analysis, LVMi (or alternatively eLVH), together with age, MR grade and the presence of mitral annular disjunction emerged as independent predictors of MR progression (Figure 2). Conclusions Patients with BD and no significant MR show an early LV and LA remodeling, together with a mild impairment of LA reservoir strain, but not of LV function. LV remodelling, and the presence of eLVH in particular, portends a higher risk of MR progression.Comparative echocardiographic analysisMultivariable Cox regression analyses

Melanocortin 1 receptor deficiency protects against pathological cardiac hypertrophy

Abstract Background The melanocortin system, including adrenocorticotropic hormone, melanocyte-stimulating hormones and five melanocortin receptors (MC-R), regulates important physiological functions such as pigmentation and energy homeostasis. It has been also recently implicated in the regulation of pathological cardiac remodeling but the role of different MC-R subtypes in the heart remain unknown. Purpose Based on the abundant cardiac expression of MC1-R, we hypothesized that it is functionally active in the heart and regulates pathological cardiac remodeling. Methods Rat H9c2 cells were used to study the effects of the selective MC1-R agonist LD211 on intracellular signaling cascades, gene expression and cellular growth response by using Western blotting, quantitative RT-PCR and 3H-leucine incorporation assay, respectively. Recessive yellow mice (Mc1re/e) were used as a model of global MC1-R deficiency. Inducible cardiomyocyte-specific MC1-R knockout mouse model (Mc1r-cKO) was engineered by intercrossing MC1-R floxed mice (Mc1rfl/fl) with tamoxifen-inducible Myh6-MerCreMer transgenic mice (Myh6-MCM). Mc1re/e and Mc1r-cKO mice were subjected to transverse aortic constriction (TAC, 8 wks) or subcutaneous infusion of angiotensin II (Ang II, 4 wks) to induce pathological cardiac hypertrophy. Cardiac structure and function were measured by echocardiography and by histological examination of H&E-stained heart sections. Results Treatment of H9c2 cells with LD211 increased MAP-kinase p-38 phosphorylation (+53 %, P=0.005 vs control), upregulated the expression of B-type natriuretic peptide (Nppb, +40 %, P=0.03 vs control) and increased 3H-leucine incorporation (+27 %, P=0.006 vs control). Mc1re/e mice showed reduction in ventricular weight (-29 mg, P=0.03) compared to WT mice after TAC operation, and reduced left ventricular (LV) expression of atrial natriuretic peptide (Nppa) and fibrosis-related genes (Ctgf and Mmp2). In terms of LV systolic performance, TAC-operated Mc1re/e mice showed tendency towards improved LV ejection fraction (EF, +6 %, P=0.06) compared to WT mice. To further investigate whether the phenotype of Mc1re/e mice is driven by deficient MC1-R signaling in cardiomyocytes, we characterized Mc1r-cKO mice, which recapitulated the phenotypic features of Mc1re/e mice. Specifically, TAC-operated Mc1r-cKO mice displayed reduced ventricular weight (-38 mg, P=0.007) and downregulation of LV expression of Nppa and fibrosis-related genes compared to Myh6-MCM mice. Likewise, in a model of Ang II-induced cardiac hypertrophy, Mc1r-cKO mice showed reduced ventricular weight (-10 mg, P=0.015) compared to Myh6-MCM mice, indicating that the protection against pathological cardiac hypertrophy was model-independent. Conclusion Our studies demonstrate that MC1-R activation promotes cardiomyocyte growth in vitro, while global and cardiomyocyte-specific MC1-R deficiency protects against pathological cardiac hypertrophy induced by TAC or Ang II infusion.

Abstract 15612: EDG-7500, a Novel Cardiac Sarcomere Regulator That Preserves Intrinsic Myosin-Motor Function, Improves Cardiac Function and Reserve in a Minipig Model of Hypertrophic Cardiomyopathy

Introduction: Hypertrophic Cardiomyopathy (HCM) is a myocardial disease characterized by LV hypertrophy, hyperdynamic contraction, and diastolic dysfunction that results in impaired exercise capacity. In HCM, excess acto-myosin crossbridge formation during diastole increases myocardial stiffness leading to hindered ventricular filling and limited cardiac reserve. EDG-7500, a novel sarcomere regulator that slows the rate of contraction but does not directly inhibit the myosin motor head, may offer salutary effects in HCM with minimal reduction in systolic performance. Here, this hypothesis was tested in the setting of the pathological HCM beta-myosin heavy chain (MYH7) R403Q mutation. Methods: In vitro, force dynamics were evaluated in human IPSC-derived engineered heart tissues (EHT) with the MYH7 R403Q mutation compared to isogenic controls (WT). The biomechanical effects of EDG-7500 were evaluated in permeabilized fibers from tissues isolated from minipigs carrying the MYH7 R403Q mutation. The in vivo cardiac responses to EDG-7500 were studied via echocardiography and invasive hemodynamics in the R403Q minipigs. In a subset of pigs, β-adrenergic receptor (β-AR) dependent cardiac output reserve was studied. Results: R403Q mutant EHT preserved peak force (PF) relative to WT but impaired relaxation kinetics (RT90: +19±4 ms, 171±4 vs. 152±2 ms in WT, P<0.05). EDG-7500 (0.3uM) accelerated relaxation kinetics in R403Q EHTs (RT90: -8±3ms, 180±4 to 172±2 ms, P<0.05) without affecting PF. RT90 improvement occurred at 6-fold lower concentrations than systolic inhibition (PF IC20: 1.95 ± 0.70 μM). In vivo, EDG-7500 improved early LV filling, accelerating e’ (6.9 ± 0.8 to 8.6 ± 0.6 cm/s, P < 0.05) and decreased atrial volume (-22%, P < 0.05) while enhancing β-AR dependent cardiac output recruitment; in R403Q pigs, EDG-7500 plus dobutamine led to higher cardiac outputs relative to only dobutamine (3.1±0.3 vs. 2.6±0.3 L/min, P<0.05). Conclusions: EDG-7500, a novel cardiac sarcomere regulator, improved diastolic function in EHT and animals with the HCM-pathogenic MYH7 R403Q mutation, improving β-AR dependent cardiac output reserve. This novel profile could be valuable for the treatment of patients with HCM and diseases of diastolic dysfunction.

Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators.

Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.

Evaluation of Left Ventricular Remodelling in Patients with Anterior Myocardial Infarction According to Sphericity and Conicity Indices and their Association with Left Ventricular Function

Background:
 Following cardiac damage, a complex process known as left ventricular adverse remodelling occurs, which is characterized by alterations in the left ventricle (LV)'s structure, form, and function. The study aims at assessing the significance of the LV sphericity index in quantifying LV geometric alterations, as well as the conicity index's significance in recognizing regional variations in LV geometry and evaluating its relation to the heart's systolic and diastolic function.
 Methods and Methods: A total of 50 individuals with anterior myocardial infarction (MI) participates in this cross-sectional study. Sphericity (SI) and conicity indices (CI) are calculated using the ratios of the short axis and long axis, and the apical to short LV axis, respectively. Then measurements of the LV's systolic and diastolic functioning are done.
 Results: The sphericity index and systolic parameters display a statistically significant negative correlation (P<0.05). The conicity index and systolic parameters show a statistically non-significant negative correlation (P>0.05).
 The relation between CI and SI with LV diastolic parameters reveal a positive correlation, but it was statistically non-significant (p>0.05). Only the left atrial volume index (LAVI) was statistically significant with SI (p<0.05).
 Conclusion: This study concludes that LV indices are a simple, non-invasive measure of LV remodelling, whether locally by CI or globally by SI, and can reflect the LV's systolic and diastolic performance based on correlation studies.

Effects of Ivabradine on Right Ventricular Systolic Function in Patients With Chronic Obstructive Pulmonary Disease and Cor Pulmonale

Cor pulmonale is a clinical syndrome associated with pulmonary hypertension, frequently complicated by congestive heart failure, commonly caused by chronic obstructive pulmonary disease (COPD). Most patients with cor pulmonale have tachycardia. However, heart rate (HR) reduction represents a primary treatment goal to improve the survival and quality of life in these patients. Ivabradine can selectively slow HR at rest and during exercise. In this prospective study, we tested the hemodynamic effects, invasively determined using right-sided cardiac catheterization, of reducing HR with ivabradine. We selected 18 patients (13 men [72.2%], mean age 67 ± 10years) with COPD and cor pulmonale, presenting with sinus tachycardia. All patients performed clinical evaluation, electrocardiogram, spirometry, echocardiogram, 6-minute walking distance, and right-sided cardiac catheterization within 1month of enrollment. All tests were repeated after 6months of ivabradine treatment (median assumed dose 11.9mg/die). We noticed a significant decrease of HR (from 98 ± 7 to 77 ± 8beats/min, p=0.0001), with a concomitant reduction of the congestion index (from 25.9 ± 5.1 to 19.4 ± 5.7mm Hg, p=0.001), and the consequent improvement of the right ventricular systolic performance (right ventricular stroke volume augmented from 56.7 ± 7.9 to 75.2 ± 8.6ml/beat, p=0.0001). This allows an improvement in clinical status and exercise tolerance (Borg scale score decreased from 5.2 ± 1.4 to 4.1 ± 1.3, p=0.01 and the 6-minute walking distance increased to 252 ± 65 to 377 ± 59m, p=0.001). In conclusion, HR reduction significantly improves hemodynamic and clinical status of patients with tachycardia affected by COPD and cor pulmonale.

Prognosis value of EAS index in patients with obstructive coronary artery disease.

EAS index is reported to be an adjunctive tool for risk stratification in addition to left ventricular ejection fraction (LVEF). This study aimed to verify the predictive value of EAS index among coronary artery disease (CAD) patients with different cardiac systolic function levels. A total of 477 patients with obstructive CAD were included in the exploratory analysis of a prospective cohort between October 2017 and January 2018 at Guangdong Provincial People's Hospital. EAS index, e'/(a' × s'), is a novel parameter assessed by tissue Doppler imaging (TDI) indicating combined diastolic and systolic performance. Any occurrence of major adverse cardiovascular event (MACE) was recorded, including first onset of myocardial infarction, stroke, readmission for heart failure, coronary revascularization, or cardiovascular death that occurred within 6 months of the first admission. Kaplan-Meier survival and Cox regression analyses were applied to testify the predictive value of EAS index for cardiovascular outcome. A total of 415 patients (87.2%) completed the follow-up (median, 25.9 months) and experienced 101 (24.3%) MACEs, 17 (4.0%) deaths, and 139 (33.4%) composite events. Elevated EAS index was significantly associated with a higher incidence of MACE, even after adjustment for age, sex, body mass index, N-terminal pro brain natriuretic peptide, high-sensitivity troponin T, high-density lipoprotein, stenosis degree, and other TDI parameters [Model 3, hazard ratio: 1.81, 95% confidence interval (CI): 1.15-2.85]. For different levels of cardiac function, Kaplan-Meier survival analysis revealed that elevated EAS index was associated with higher MACE incidence only in patients with LVEF ≥50% (P<0.05). EAS index is an independent predictor of MACE in patients with obstructive CAD, which could be utilized as a tool for risk stratification in CAD patients or incorporated into a prediction model to improve efficacy.

Right Ventricular Response to Cardiac Resynchronization Therapy: A Three-Dimensional and Speckle Tracking Echocardiographic Study

Cardiac resynchronization therapy (CRT) induces left ventricle reverse remodeling; however, its effects on right ventricular (RV) volumes and function were not well described. This study aimed to assess the effects of CRT on RV. Of 112 patients, 63 enrolled with a mean age of 62.77±7.23years, including 40 males (63.5%). All patients met criteria for CRT implantation and were followed at 3-month and 6-month intervals. Standard 2-dimensional/3-dimensional (3D) echocardiography and speckle-tracking analyses were conducted for assessment of LV and left atrium (LA). RV maximum diameters, tricuspid lateral annular systolic velocity, tricuspid annular plane systolic excursion, fractional area change, RV global (RV 4-chamber strain (RV4CSL), and RV free wall strain (RVFWSL), in addition to 3D echocardiographic assessment of RV, were done before CRT implantation and at follow-up visits. Mean follow-up period was 6.76±1.25months. A total of 48 patients (76.2%) were LV responders (LVR) whereas the rest were nonresponders (LVNR). Both groups had similar baseline characteristics, risk factors, device implantation, and programming values. Only LVR had significant reduction in RV basal diameter, together with significant improvement of RV systolic performance: systolic velocity, fractional area change, RV4CSL, RVFWSL, and 3D-derived RV volumes and ejection fraction, compared with baseline values. In addition, pulmonary arterial systolic pressure decreased in LVR with reduction of tricuspid regurgitation severity. LV response, percentage change of RV4CSL, LA end-systolic volume index, and LA emptying fraction at 3-month follow-up were the most independent predictors of RV response by multivariate analysis. Reduced left ventricular end-systolic volume >13.5% had 92.3% sensitivity and 81.8% specificity. In conclusion, CRT-induced RV reverse remodeling and improved RV-arterial coupling. These effects were associated with left side response to CRT.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding – A Multicenter Nationwide Study

Introduction: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). Methods: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. Results: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. Conclusions: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Topographical Association Between Left Ventricular Strain and Brain Lesions in Patients With Acute Ischemic Stroke and Normal Cardiac Function.

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Bioinspired polymeric heart valves: A combined in vitro and in silico approach

BackgroundPolymeric heart valves (PHVs) may address the limitations of mechanical and tissue valves in the treatment of valvular heart disease. In this study, a bioinspired valve was designed, assessed in silico, and validated by an in vitro model to develop a valve with optimum function for pediatric applications. MethodsA bioinspired heart valve was created computationally with leaflet curvature derived from native valve anatomies. A valve diameter of 18 mm was chosen to approach sizes suitable for younger patients. Valves of different thicknesses were fabricated via dip-coating with siloxane-based polyurethane and tested in a pulse duplicator for their hydrodynamic function. The same valves were tested computationally using an arbitrary Lagrangian–Eulerian plus immersed solid approach, in which the fluid–structure interaction between the valves and fluid passing through them was studied and compared with experimental data. ResultsComputational analysis showed that valves of 110 to 200 μm thickness had effective orifice areas (EOAs) of 1.20 to 1.30 cm2, with thinner valves exhibiting larger openings. In vitro tests demonstrated that PHVs of similar thickness had EOAs of 1.05 to 1.35 cm2 and regurgitant fractions (RFs) <7%. Valves with thinner leaflets exhibited optimal systolic performance, whereas thicker valves had lower RFs. ConclusionsBioinspired PHVs demonstrated good hydrodynamic performance that exceeded ISO 5840-2 standards. Both methods of analysis showed similar correlations between leaflet thickness and valve systolic function. Further development of this PHV may lead to enhanced durability and thus a more reliable heart valve replacement than contemporary options.

A Study on Evaluation of Relationship between Left Atrial Volume and Diastolic Dysfunction in Bangladeshi Patients

Background: An increase in the left atrial volume index (LAVI) has been recognized as an important indicator of left ventricular (LV) diastolic dysfunction (DD), which is considered a significant risk factor for cardiovascular events. The left atrium plays a crucial role in maintaining efficient cardiac function by facilitating proper blood flow between the pulmonary veins and the left ventricle during diastole. Objective: In this study our main goal is to evaluate the relationship between Left Atrial Volume and Diastolic Dysfunction in 500 Bangladeshi Patients. Method: From January 2022 to January 2023, researchers at a tertiary hospital in Bangladesh analyzed data from 500 patients in need of a transthoracic echo in the cardiology department. Patients were people aged 20 to 86 with a history free of atrial or ventricular arrhythmias, pacemaker usage, valvular disease (other than minor), or congenital cardiopathy who presented with sinus rhythm. Forty-five people were left out because their tests were either too limited to assess mitral diastolic flow (n = 35) or too limited to assess left atrial volume index (n = 10). Five hundred patients were used as the study's final sample size. Results: The average age and proportion of men in the DD groups were both greater than in the normal function group. The DD groups had more left ventricular mass than the controls. Only in the group with ventricular filling limitation pattern (grade III DD), was the ejection fraction significantly decreased. LAVI and dimensions both rose as DD severity increased, from 21 4.2 mL/m2 in grade I to 26.1 7.5 mL/m2 in grade II to 50.4 2.8 mL/m2 in grade III (p 0.001). In addition, the grade I DD groups (altered relaxation) showed a relative decrease in the E-wave and the E/A ratio, and an increase in the mitral deceleration time, when compared to the normal diastolic function group; the opposite was seen in the group with grade III DD (restrictive pattern). All DD subtypes had weaker e' waves compared to those with normal diastolic function. As DD progressed, a rise in the E/e' ratio was seen. LAVI was positively correlated with age, left ventricular (LV) diastolic and systolic volumes, LV wall relative thickness, LV mass indexed to height raised to the 2.7th power, and E/e' ratio (all p 0.01). There was a statistically significant negative relationship between left atrial volume index and left ventricular ejection fraction, as well as between the e' wave and the septal mitral anulus. Conclusion: According to this study in a Bangladeshi population, DD contributes to left atrial remodelling, and a rise in LAVI is an indicator of DD severity. In this cohort with preserved or slightly reduced mean ejection fraction and no substantial valvular heart disease, LAVI increase determinants are related to age, left ventricular hypertrophy, higher filling pressure, and impaired LV systolic performance.

Trastuzumab-Induced Cardiac Dysfunction. A Case Report

Oncological pathology and the management of patient with cancer are real challenges in cardiology practice. Unpredictable situations triggered by this pathology, as well as adverse reactions of oncological therapy on the cardiovascular system, are increasing. A 71-year-old female patient who was known with HER2-positive breast cancer, with sectorial mastectomy and treated with chemo-radio-immunotherapy in 2018, then diagnosed with liver metastases and ulcerated gastric adenocarcinoma in May 2022, was referred to the Cardiology Clinic for chest pain and dyspnea. On the ECG, ST-segment depression was seen in the infero-lateral territory. Positive myocardial necrosis enzymes were documented, and also moderate microcytic hypochromic anemia. The current clinical, electrical, and biological picture was suggestive for acute coronary syndrome. It should be mentioned that the patient has been on monoclonal antibody therapy with Trastuzumab, recently discontinued after echocardiographic evaluation where decreased systolic performance was noted. Considering all the particular aspects of this case, as cardiotoxicity of oncological therapy, acute coronary event and anemic syndrome, multidisciplinary management is required, with adjustment of cardiovascular therapy and cancer treatment.

Effect of resistance exercise on cardiac perturbations and systolic performance: A cross-over randomized trial comparing volumes and techniques

ABSTRACT This study investigated the magnitude and time-course of resistance exercise (RE) technique induced transient cardiac perturbations. Twenty-four participants were assigned to one of four arms: sets to failure or non-failure with 8–10 repetition maximum (RM), and sets to failure or non-failure with 15RM. Echocardiographic and blood pressure (BP) data were recorded at baseline and 30 min, 6 h and 24 h post-exercise. In all groups end-systolic circumferential wall stress (cESS), and ratio of transmitral inflow velocities (E/A) were significantly decreased while posterior wall thickness (PWT), global circumferential strain (GCS), GCS strain rate (GCSR), global longitudinal strain rate (GLSR), and stroke volume (SV) were significantly increased for up to 6 h of follow-up. In the 15RM groups, left ventricular (LV) mass and interventricular septal thickness (IVST) were significantly increased, and left atrial (LA) area was significantly decreased (p < 0.05) compared to the 8–10 RM groups. In the 15RM groups, RE decreased global longitudinal strain (GLS) and increased ejection fraction (EF) (p<0.01). After RE, transient cardiac perturbations, the reduction in LA compliance, and the improvement in LV myofibril geometry were volume dependent and influenced more by sets to failure technique. RE increased GCS and reduced the afterload, thus helping to preserve SV and EF.

Evaluation of Left Ventricular Systolic Function Using Layer-Specific Strain in Rats Performing Endurance Exercise: A Pilot Study.

The functional characteristics of exercise-induced myocardial hypertrophy were studied in a rat model in conjunction with ultrasound layered strain technique to investigate the hidden changes in the heart brought about by exercise. Forty specific pathogen free (SPF) adult Sprague-Dawley rats were selected and randomly divided into two groups of 20 exercise and 20 control rats. The longitudinal and circumferential strain parameters were measured using the ultrasonic stratified strain technique. The differences between the two groups and the predictive effect of stratified strain parameters on left ventricular systolic function were analyzed. The exercise group had significantly higher global endocardial myocardial longitudinal strain (GLSendo), global mid-myocardial global longitudinal strain (GLSmid) and global endocardial myocardial global longitudinal strain (GCSendo) values than the control group (p < 0.05). Even though global mid-myocardial circumferential strain (GCSmid) and global epicardial myocardial circumferential strain (GCSepi) were higher in the exercise group than in the control group, statistical significance was not reached (p > 0.05). Conventional echocardiography parameters were well correlated with GLSendo, GLSmid, and GCSendo (p < 0.05). GLSendo was the best predictor of left ventricular myocardial contractile performance in athletes determined using the receiver operating characteristic curve, with an area under the curve of 0.97, sensitivity of 95% and specificity of 90%. Rats performing endurance exercise exhibited subclinical changes in the heart after prolonged high-intensity exercise. A stratified strain parameter, GLSendo, played an important role in the evaluation of LV systolic performance in exercising rats.

Left and right ventricular function by echocardiography, tissue doppler imaging, carotid intima media thickness, and asymmetric dimethylarginine levels in female adolescents with vitamin D deficiency.

The aim of our study was to assess left and right ventricle systolic and diastolic functions in female adolescents with vitamin D deficiency using conventional echocardiography and pulsed-wave tissue Doppler imaging and to investigate carotid intima media thickness and asymmetric dimethylarginine levels. Sixty-six female adolescents were enrolled in this study. The female adolescents were divided into a vitamin D deficiency group (n: 34) and a control group (n: 32). All subjects underwent laboratory blood tests, including asymmetric dimethyl arginine, complete two-dimensional, pulse, and tissue Doppler echocardiography, and measurement of the carotid intima-media thickness. The vitamin D-deficient female adolescent group had normal left and right ventricle systolic and diastolic functions and normal global systolic and diastolic myocardial performance. In the patients with vitamin D deficiency, the carotid intima-media thickness was higher than that in the controls. In the patients within the vitamin D deficiency group, vitamin D was found to be positively correlated with magnesium and negatively correlated with phosphorus and left atrial dimension. The results of this study demonstrate that vitamin D deficiency in female adolescence is associated with normal myocardial geometry and function. Although it has been associated with normal levels of asymmetric dimethyl arginine concentration, high measured carotid intima-media thickness may reflect endothelial dysfunction.