Myocardial Wall Stress Research Articles

Early left atrial reverse remodelling in patients with hypertrophic obstructive cardiomyopathy receiving transapical beating-heart septal myectomy.

This study aims to investigate the short-term effects of transapical beating-heart septal myectomy (TA-BSM) on left atrial (LA) anatomy and function and its association with clinical indicators in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 105 HOCM patients who received TA-BSM were included. Clinical and comprehensive echocardiographic data were obtained before surgery, at discharge, and 3 months after myectomy. LA reverse remodelling was defined as LA maximum volume index (LAVI) ≤34 ml/m2 and a change of ≥10%. At 3 months after TA-BSM, New York Heart Association (NYHA) functional class and 6-min walking test were significantly improved, N-terminal pro-B-type natriuretic peptide (NT-proBNP) decreased, left ventricular outflow tract (LVOT) peak gradient and mitral regurgitation were significantly reduced. LAVI decreased in 76%, with a median change of 20%, and the criteria for LA reverse remodelling were met in 48%. LA strain parameters were improved at 3 months after TA-BSM. Moreover, left ventricular (LV) diastolic function was significantly improved, but LV global longitudinal strain was not significantly changed at 3 months after operation. Improvement in LVOT peak gradient, LAVI, LA reservoir strain (LASr) and conduit strain (LAScd) were associated with reduction in NT-proBNP. Along with effectively relieving the obstruction of the LVOT and mitral regurgitation, TA-BSM could significantly improve LA size and function during the short-term follow-up for HOCM patients. The indicators of LA reverse remodelling were associated with reduction in a biomarker of myocardial wall stress, indicating the early recovery of LV relaxation and clinical status for patients.

Injectable Hydrogels in Cardiovascular Tissue Engineering.

Heart problems are quite prevalent worldwide. Cardiomyocytes and stem cells are two examples of the cells and supporting matrix that are used in the integrated process of cardiac tissue regeneration. The objective is to create innovative materials that can effectively replace or repair damaged cardiac muscle. One of the most effective and appealing 3D/4D scaffolds for creating an appropriate milieu for damaged tissue growth and healing is hydrogel. In order to successfully regenerate heart tissue, bioactive and biocompatible hydrogels are required to preserve cells in the infarcted region and to bid support for the restoration of myocardial wall stress, cell survival and function. Heart tissue engineering uses a variety of hydrogels, such as natural or synthetic polymeric hydrogels. This article provides a quick overview of the various hydrogel types employed in cardiac tissue engineering. Their benefits and drawbacks are discussed. Hydrogel-based techniques for heart regeneration are also addressed, along with their clinical application and future in cardiac tissue engineering.

Heart Failure and Echocardiography Derived Myocardial Wall Stress Link in Diabetic Cases with Acute Myocardial Infarction Managed by Revascularization.

Diabetes is associated with left ventricular remodeling. Myocardial wall stress is a measurable factor connected to the ventricular breadth and force and is related to myocardial thickness; it can be measured by echocardiography. The present study aimed to assess the link between heart failure (HF) and echocardiography-derived myocardial wall stress in diabetic patients with ST elevation myocardial infarction (STEMI) who were managed with revascularization. This study was a comparative prospective study that took place between February 2022 and February 2023. It included 100 diabetic patients presented with STEMI and managed by percutaneous coronary intervention (PCI). Patients were selected from the cardiology departments at Al-Azhar University Hospital, Damietta, Egypt. During the hospital stay, patients were checked for HF symptoms and signs. They were also observed for 3 months after discharge for detection of HF. Those who did not develop HF were assigned to group I, and those with HF were assigned to group II. The mean value of end-systolic wall stress (ESWS) was 77.09 ± 12.22 and 97 ± 13.44, and the mean value of end-diastolic wall stress (EDWS) was 12.61 ± 2.76 and 15.87 ± 2.86 in groups I and II respectively, with significant differences between the 2 groups. The cutoff point to detect HF was 88 KPa for ESWS and 13.5 KPa for EDWS, with a sensitivity of 70% and 79% and a specificity of 80% and 61% for ESWS and EDWS, respectively. Elevated left ventricle (LV) myocardial stress is related to increased HF in diabetic patients whose HF was managed by PCI after STEMI. LV wall stress is a potentially helpful risk stratification tool using routine echocardiography to determine the treatment plane according to the risk status.

Systemic Hemodynamics, Cardiac Mechanics, and Signaling Pathways Induced by Extracorporeal Membrane Oxygenation in a Cardiogenic Shock Model.

Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in patients suffering from refractory cardiogenic shock (CS). Although considered life-saving, peripheral VA-ECMO may also be responsible for intracardiac hemodynamic changes, including left ventricular overload and dysfunction. Venoarterial extracorporeal membrane oxygenation may also increase myocardial wall stress and stroke work, possibly affecting the cellular cardioprotective and apoptosis signaling pathways, and thus the infarct size. To test this hypothesis, we investigated the effects of increasing the peripheral VA-ECMO blood flow (25-100% of the baseline cardiac output) on systemic and cardiac hemodynamics in a closed-chest CS model. Upon completion of the experiment, the hearts were removed for assessment of infarct size, histology, apoptosis measurements, and phosphorylation statuses of p38 and protein Kinase B (Akt), and extracellular signal-regulated kinase mitogen-activated protein kinases (ERK-MAPK). Peripheral VA-ECMO restored systemic perfusion but induced a significant and blood flow-dependent increase in left ventricular preload and afterload. Venoarterial extracorporeal membrane oxygenation did not affect infarct size but significantly decreased p38-MAPK phosphorylation and cardiac myocyte apoptosis in the border zone.

Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New.

Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice.

Abstract 13612: Association Between B-Type Natriuretic Peptide and Inferior Vena Cava Diameter as a Measure of Hypovolemia in Cancer Patients

Introduction: Hypovolemia is frequently seen in cancer patients due to catabolism, cachexia, and decreased oral intake. However, volume status assessment in this population is often difficult due to competing comorbid conditions such as edema. Elevated B-type natriuretic peptide (BNP) is an established biomarker of myocardial wall stress in patients with hypervolemia. We sought to determine if very low BNP could be an objective marker of hypovolemia in cancer patients Hypothesis: In cancer patients undergoing treatment, is low BNP level (<10 pg/mL) associated with small inferior vena cava (IVC) diameter (< 1.4 cm) - an established marker of hypovolemia on transthoracic echocardiography (TTE)?We hypothesize that BNP <10 pg/mL is associated with small IVC as a marker of hypovolemia in cancer patients. Methods: We conducted a retrospective study (N=91) with solid malignancies, undergoing chemo- and/or radiation therapy (RT), divided into 3 groups based on BNP values in pg/mL: low (BNP <10), normal (BNP 10-100) and high (BNP>100). Retrospective data were obtained between 2016-2023 from Rush University Medical Center Cardio-Oncology Registry. IVC measurements by 2 medial trainees (Cohen’s intraclass correlation coefficient = 0.87, p < 0.01) were acquired from formal TTEs obtained within 1 week of BNP measurements. Linear regression was used to calculate the adjusted means (for age, sex, BMI, blood pressure, creatinine, RT, TSH) of the 2 measured IVC diameters per datapoint. Mean difference in IVC diameters was compared between the 3 BNP groups. Results: The population mean age was 59.99 ± 12.19, 67% women. Adjusted mean IVC measurements were 1.89cm, 1.55cm, and 1.26cm for the high, normal, and low BNP groups respectively. The mean difference in IVC diameters between high and low BNP groups was 0.628 ±0.164 cm (p<0.01). Conclusions: In cancer patients undergoing treatment, very low BNP (<10pg/mL) was associated with small IVC as a marker of hypovolemia. In this group of patients, BNP measured with routine lab data is a readily available tool to identify individuals with hypovolemia where other measures of volume status such as physical exams might be uncertain.

Abstract 14391: Biomarkers, Proteomics, and Echocardiography Lend Insights into Cardiovascular Death in HFrEF: A VICTORIA Substudy

Background: Using data from the VICTORIA ECHO substudy in high-risk patients with heart failure with reduced ejection fraction (HFrEF), we evaluated the potential complementary role of cardiac function, biomarkers, and proteomics in association with cardiovascular death (CVD), a key component of the primary composite (HF hospitalization or CVD). Hypothesis: Measurement of cardiac biomarkers, proteins, and ECHO parameters may provide insights into the mechanism of CVD in HFrEF. Methods: At baseline, left ventricular ejection fraction (LVEF) and LV end-systolic volume index (LVESVI) on ECHO, 6 quantitative biomarkers, and 92 proteins (Olink CVD III panel) were assessed by blinded core labs. Adjusted (MAGGIC) associations and HRs (95% CIs) are presented. Proteomics associations were adjusted for false discovery rate. Results: Of 583 patients, 96 (16.5%) had CVD (21.6/100 pt-years) a median 8 months (IQR 6-11) from randomization. See Table for MAGGIC-adjusted HRs for LVEF, LVESVI, and biomarkers. NT-proBNP was most strongly associated with CVD (HR per doubling 1.53 [1.32-1.77]). Proteins significantly associated with CVD were cathepsin D (2.32 [1.62-3.32]), matrix metalloproteinase-2 (2.31 [1.45-3.68]), IL-2 receptor (1.74 [1.40-2.14]), transferrin receptor (1.64 [1.31-2.04]) and tumor necrosis superfamily (1.88 [1.41-2.50]) (Fig). Conclusions: After MAGGIC adjustment, a rise in LVESVI, but not LVEF, was associated with CVD. Upregulation of selected biomarkers/proteins related to myocardial wall stress, extracellular matrix turnover, inflammation, and oxidative stress were also associated with CVD and may serve as novel future therapeutic targets in HFrEF.

Is COPD the Determinant Factor for Myocardial Injury and Cardiac Wall Stress in OSA Patients?

Background and Objectives: Evidence shows that COPD-OSA overlap syndrome (OS) is more frequently accompanied by cardiovascular disease (CVD) in comparison to either disease alone. The aim of the study was to explore whether patients with OS have a higher burden of subclinical myocardial injury and wall stress compared with OSA patients. Materials and Methods: Consecutive patients, without established CVD, underwent polysomnography and pulmonary function testing, due to suspected sleep-disordered breathing. An equal number of patients with OS (n = 53, with an apnea hypopnea index (AHI) > 5/h and FEV1/FVC < 0.7) and patients with OSA (n = 53, AHI > 5/h and FEV1/FVC > 0.7) were included in the study. The detection of asymptomatic myocardial injury and wall stress was performed via the assessment of serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), respectively. Results: OS patients were older (p < 0.001) and had worse hypoxemic parameters, namely average oxyhemoglobin saturation (SpO2) (p = 0.002) and time spent with SpO2 < 90% (p = 0.003) during sleep as well as daytime pO2 (p < 0.001), than patients with OSA. No difference was observed between groups in terms of Epworth Sleepiness Scale (p = 0.432) and AHI (p = 0.587). Both levels of hs-cTnT (14.2 (9.1-20.2) vs. 6.5 (5.6-8.7) pg/mL, p < 0.001) and NT-proBNP (93.1 (37.9-182.5) vs. 19.2 (8.3-35.4) pg/mL, p < 0.001) were increased in OS compared to OSA patients. Upon multivariate linear regression analysis, levels of NT-proBNP and hs-cTnT correlated with age and average SpO2 during sleep. Conclusions: Our study demonstrated higher levels of hs-cTnT and NT-proBNP in OS patients, indicating an increased probability of subclinical myocardial injury and wall stress, compared with OSA individuals.

Transcatheter Left Ventricular Restoration in Patients With Heart Failure

BackgroundLeft ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. Methods and ResultsWe analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). ConclusionsIn patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Biomarkers, Socioeconomic Factors, and Right Ventricular Function After Surgical Repair for Tetralogy of Fallot.

Right ventricular (RV) dysfunction early after tetralogy of Fallot (TOF) increases post-operative morbidity. We investigated associations of circulating biomarkers and socioeconomic factors with early post-operative RV systolic function. Single-center prospective cohort study of infants undergoing TOF repair. Six serologic biomarkers of myocardial fibrosis and wall stress collected at the time of surgery were measured with immunoassay. Geocoding was performed for socioeconomic factors. Multivariate adaptive regression splines (MARS) models identified factors associated with RV function parameters: fractional area change (FAC), global longitudinal strain and strain rate, andfree wall strain and strain rate. Seventy-one patients aged 3.5months (IQR 2.4, 5.2) were included. Galectin-3 was the highest ranked predictor for FAC, global longitudinal strain, and free wall strain, and procollagen type-I carboxy-terminal propeptide (PICP) was the highest ranked predictor for global longitudinal strain rate and free wall strain rate. Several neighborhood characteristics were also highly ranked. Models adjusted R2 ranged from 0.71 to 0.85 (FAC, global longitudinal strain/strain rate), and 0.55-0.57 (RV free wall strain/strain rate). A combination of serologic biomarkers, socioeconomic, and clinical variables explain a significant proportion of the variability in RV function after TOF repair. These factors may inform pre-operative risk-stratification for these patients.

The Role of Hydrogel in Cardiac Repair and Regeneration for Myocardial Infarction: Recent Advances and Future Perspectives

A myocardial infarction (MI) is the leading cause of morbidity and mortality, seriously threatens human health, and becomes a major health burden of our society. It is urgent to pursue effective therapeutic strategies for the regeneration and restore myocardial function after MI. This review discusses the role of hydrogel in cardiac repair and regeneration for MI. Hydrogel-based cardiac patches and injectable hydrogels are the most commonly used applications in cardiac regeneration medicine. With injectable hydrogels, bioactive compounds and cells can be delivered in situ, promoting in situ repair and regeneration, while hydrogel-based cardiac patches reduce myocardial wall stress, which passively inhibits ventricular expansion. Hydrogel-based cardiac patches work as mechanically supportive biomaterials. In cardiac regeneration medicine, clinical trials and commercial products are limited. Biomaterials, biochemistry, and biological actives, such as intelligent hydrogels and hydrogel-based exosome patches, which may serve as an effective treatment for MI in the future, are still under development. Further investigation of clinical feasibility is warranted. We can anticipate hydrogels having immense translational potential for cardiac regeneration in the near future.

Effects of Breed, Exercise, and a Two-Month Training Period on NT-proBNP-Levels in Athletic Dogs.

N-terminal pro-b-type natriuretic peptide (NTproBNP) is a cardiac biomarker used to detect myocardial wall stress. Physical activity and cardiac disease can affect serum NTproBNP concentrations. In people, different types of physical activity have different effects on NTproBNP. Our hypothesis was that physical activity and training have an effect on NTproBNP concentrations depending on the type of exercise and the intensity. Seven German Shepherd dogs (GSD) under military training performing short bursts of fast-paced interval exercise and seven Eurohounds (EHs) training for racing competition with endurance exercise were included in the study. Blood samples were taken at enrollment (T0) and after a two-month (T2mth) training period; on both occasions, the samples were acquired before and after physical exercise. An echocardiographic evaluation was performed at T0. Echocardiographic heart size was larger in the EHs compared to the GSDs. The NTproBNP concentration was higher in the EHs than in the GSDs before and after exercise at T0 and T2mth. Echocardiographic parameters of heart size and wall thickness correlated with NTproBNP at T0 before and after exercise. Exercise induced an elevation of NTproBNP in the EHs at T0 and T2mth, while in the GSDs this was observed only at T0. In the EHs, post exercise was associated with higher NTproBNP at T2mth compared to T0, while in the GSDs the opposite pattern was noticed. From our study, the serum NTproBNP concentration differs between breeds. Intense physical activity causes an increase in NTproBNP. A two-month training period does not affect the NTproBNP concentration at rest. Intense physical activity may increase NTproBNP above the reference range in individual dogs.

Focused ultrasound stimulation of the inflammatory reflex at the spleen ameliorates pulmonary arterial hypertension in rodents

Abstract Background Inflammation is a major contributor in pulmonary arterial hypertension (PAH) pathogenesis. Non-invasive, focused ultrasound stimulation (FUS) of the spleen activates the neuroimmune inflammatory reflex (IR) and suppresses systemic inflammation [1]. Purpose We aimed to explore whether daily FUS of the spleen improves haemodynamics and biomarkers by modulating the IR, in a rat model of PAH. Methods Sprague-Dawley rats (n=12) were injected s.c. with Sugen5416 (VEGF receptor inhibitor) and then, were placed in a hypoxic chamber (FiO2=10%) for 21 days, followed by 14 days of re-exposure to normoxia (FiO2=10%). At day 21, rats were randomized to either FUS (n=6) or sham-stimulation of the spleen (n=6). Each FUS- or sham-stimulation session consisted of 12 minutes. After 14 days of treatment, in a terminal experiment, right ventricular systolic pressure (RVSP) and arterial pressure were measured invasively, as well as biomarkers, in each animal (Figure 1A). Results FUS significantly reduced RVSP compared with the sham-stimulation (Mean±SEM, 50.83±3.57 mmHg vs 72.50±5.81; p=0.009), resulting in a 30% relative reduction (Figure 1B). Mean systemic arterial pressure was similar in the 2 groups (Mean±SEM, 79.83±3.73 mmHg vs. 87.00±2.95; p=0.137) (Figure 1C), as was the change in heart rate between day 1 and day 14 of treatment period (−19.53±5.36% vs. −16.79±3.1, p=0.61) (Figure 1D). Consistently, plasma brain natriuretic peptide (BNP) levels are reduced in the FUS group (119.45±19.93 ng/μl vs. 319.39±91.85; p=0.019), indicative of reduced myocardial wall stress in the FUS group (Figure 1E). Conclusion Non-invasive FUS of the spleen reduced RVSP by ∼30% and BNP without significantly affecting systemic pressure or heart rate, in rats with severe PAH. Non-invasive FUS, by modulating the IR, may exert an anti-inflammatory effect in PAH. FUS of the spleen is noninvasive, safe, widely available and easy to perform, and should be further explored as a possible therapeutic option in PAH. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Northwell Health

Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model.

Variants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart’s contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant’s total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model.

Conductive and Semiconductive Nanocomposite-Based Hydrogels for Cardiac Tissue Engineering.

Cardiovascular disease is the leading cause of death worldwide and the most common cause is myocardial infarction. Therefore, appropriate approaches should be used to repair damaged heart tissue. Recently, cardiac tissue engineering approaches have been extensively studied. Since the creation of the nature of cardiovascular tissue engineering, many advances have been made in cellular and scaffolding technologies. Due to the hydrated and porous structures of the hydrogel, they are used as a support matrix to deliver cells to the infarct tissue. In heart tissue regeneration, bioactive and biodegradable hydrogels are required by simulating native tissue microenvironments to support myocardial wall stress in addition to preserving cells. Recently, the use of nanostructured hydrogels has increased the use of nanocomposite hydrogels and has revolutionized the field of cardiac tissue engineering. Therefore, to overcome the limitation of the use of hydrogels due to their mechanical fragility, various nanoparticles of polymers, metal, and carbon are used in tissue engineering and create a new opportunity to provide hydrogels with excellent properties. Here, the types of synthetic and natural polymer hydrogels, nanocarbon-based hydrogels, and other nanoparticle-based materials used for cardiac tissue engineering with emphasis on conductive nanostructured hydrogels are briefly introduced.

Left ventricular active strain energy density is a promising new measure of systolic function

The left ventricular ejection fraction does not accurately predict exercise capacity or symptom severity and has a limited role in predicting prognosis in heart failure. A better method of assessing ventricular performance is needed to aid understanding of the pathophysiological mechanisms and guide management in conditions such as heart failure. In this study, we propose two novel measures to quantify myocardial performance, the global longitudinal active strain energy (GLASE) and its density (GLASED) and compare them to existing measures in normal and diseased left ventricles. GLASED calculates the work done per unit volume of muscle (energy density) by combining information from myocardial strain and wall stress (contractile force per unit cross sectional area). Magnetic resonance images were obtained from 183 individuals forming four cohorts (normal, hypertension, dilated cardiomyopathy, and cardiac amyloidosis). GLASE and GLASED were compared with the standard ejection fraction, the corrected ejection fraction, myocardial strains, stroke work and myocardial forces. Myocardial shortening was decreased in all disease cohorts. Longitudinal stress was normal in hypertension, increased in dilated cardiomyopathy and severely decreased in amyloid heart disease. GLASE was increased in hypertension. GLASED was mildly reduced in hypertension (1.39 ± 0.65 kJ/m3), moderately reduced in dilated cardiomyopathy (0.86 ± 0.45 kJ/m3) and severely reduced in amyloid heart disease (0.42 ± 0.28 kJ/m3) compared to the control cohort (1.94 ± 0.49 kJ/m3). GLASED progressively decreased in the hypertension, dilated cardiomyopathy and cardiac amyloid cohorts indicating that mechanical work done and systolic performance is severely reduced in cardiac amyloid despite the relatively preserved ejection fraction. GLASED provides a new technique for assessing left ventricular myocardial health and contractile function.

B-Type Natriuretic Peptide (BNP) Revisited—Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?

Simple SummaryActive BNP-32, less active proBNP-108, and inactive N-terminal proBNP-76 all circulate in the blood. The circulating protease neprilysin has lower substrate specificity for BNP than ANP, while proBNP and N-terminal proBNP are not degraded by neprilysin. Currently available BNP immunoassays react with both mature BNP and proBNP; therefore, measured plasma BNP is mature BNP + proBNP. Because ARNI administration increases mature BNP, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI administration reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase of mature BNP due to inhibition of degradation by neprilysin, resulting in lower plasma BNP levels. In the ARNI era, BNP remains a useful biomarker for heart failure, though mild increases early during ARNI administration should be taken into consideration.Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.

Transinnominate Impella 5.5 insertion as a bridge to transplantation in a pediatric patient in refractory cardiogenic shock.

Transinnominate Impella 5.5 insertion as a bridge to transplantation in a pediatric patient in refractory cardiogenic shock.

Markers of Focal and Diffuse Nonischemic Myocardial Fibrosis Are Associated With Adverse Cardiac Remodeling and Prognosis in Patients With Hypertension: The REMODEL Study.

Background:The prognostic significance of focal and diffuse myocardial fibrosis in patients with cardiovascular risk factors is unclear.Methods:REMODEL (Response of the Myocardium to Hypertrophic Conditions in the Adult Population) is an observational cohort of asymptomatic patients with essential hypertension. All participants underwent cardiovascular magnetic resonance to assess for myocardial fibrosis: nonischemic late gadolinium enhancement (LGE), native myocardial T1, postcontrast myocardial T1, extracellular volume fraction including/excluding LGE regions, interstitial volume (extracellular volume×myocardial volume), and interstitial/myocyte ratio. Primary outcome was a composite of first occurrence acute coronary syndrome, heart failure hospitalization, strokes, and cardiovascular mortality. Patients were recruited from February 2016 and followed until June 2021.Results:Of the 786 patients with hypertension (58±11 years; 39% women; systolic blood pressure, 130±14 mm Hg), 145 (18%) had nonischemic LGE. Patients with nonischemic LGE were more likely to be men, have diabetes, be current smokers, and have higher blood pressure (P<0.05 for all). Compared with those without LGE, patients with nonischemic LGE had greater left ventricular mass (66±22 versus 49±9 g/m2; P<0.001), worse multidirectional strain (P<0.001 for all measures), and elevated circulating markers of myocardial wall stress and myocardial injury, adjusted for potential confounders. Twenty-four patients had primary outcome over 39 (30–50) months of follow-up. Of all the cardiovascular magnetic resonance markers of myocardial fibrosis assessed, only nonischemic LGE (hazard ratio, 6.69 [95% CI, 2.54–17.60]; P<0.001) and indexed interstitial volume (hazard ratio, 1.11 [95% CI, 1.04–1.19]; P=0.002) demonstrated independent association with primary outcome.Conclusions:In patients with hypertension, myocardial fibrosis on cardiovascular magnetic resonance is associated with adverse cardiac remodeling and outcomes.

Stress relaxation behavior of left ventricular myocardium in mice

BackgroundMyocardial tissues are known to exhibit viscoelastic behavior, i.e., the myocardial wall stress is gradually decaying when stretched at a constant level, referred to as stress relaxation behavior. The study of this behavior becomes important in structural heart diseases, where both passive and active relaxation behaviors of the myocardium may alter. As myocardial tissues display a complex, 3D micro‐architecture, the anisotropy of stress relaxation remains understudied. Our objective in this study was to investigate the anisotropy of (passive) stress relaxation behavior of the left ventricular (LV) myocardium in healthy small animals.MethodsWe used biaxial stress relaxation tests in wild‐type murine specimens (n=2). Full‐thickness myocardium LV free wall (LVFW) specimens were isolated from the mouse hearts (Fig. 1a), with the slab edges being aligned with the longitudinal (apex‐to‐outflow‐tract), circumferential, and radial directions of the LV. The specimens were mounted in a biaxial mechanical testing machine along the circumferential and longitudinal directions. The specimens were stretched in three different loading protocols with circumferential‐to‐longitudinal strain ratios of 30:30, 15:30, and 30:15%. The samples were loaded to the peak strain at a rate of 0.01 s‐1 and held at this stretch for 10 minutes to allow the relaxation. The time‐varying stress was recorded. We used an exponential decay fit to estimate the stress relaxation time constants in both directions.ResultsStress relaxation time constants showed noticeable differences between multiple loading ratios with equibiaxial loading (30:30) having the largest relaxation time constant followed by the circumferential stress in the 30:15 ratio (Fig. 1b). The larger strains led to larger stress relaxation constants (Fig. 1b‐c) indicating a strain‐dependent viscoelastic behavior. The quasi‐static equibiaxial loading of the same specimens resulted in a nearly isotropic behavior (not shown here), exhibiting insignificant contrast between the stresses in the circumferential and longitudinal directions. Interestingly, the contrast in the relaxation behavior between the circumferential and longitudinal directions were similarly insignificant (Fig. 1b). Non‐equibiaxial loadings (15:30 and 13:50) showed significantly faster relaxation for the direction with smaller strains (Fig. 1b).ConclusionsMyocardial tissue viscoelasticity is an important behavior contributing to both diastolic and systolic cardiac function, which remains understudied, especially in case of structural heart diseases associated with impaired relaxation in the LV. Our study suggests that stress relaxation behavior is prominent in the LV myocardium and may exhibit different relaxation behavior depending on strain magnitudes and strain ratios along different directions. The level of anisotropy in stress relaxation was found to be similar to the level of anisotropy in the tissue quasi‐static behavior. These results serve to motivate further studies to fully characterize the viscoelastic behavior of LV myocardium and its contribution to the LV relaxation and filling in murine models of LV diseases.