Myocardial Structural Changes Research Articles

Cardiac dysfunction in patients with cirrhosis and acute decompensation.

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.

Clinical characteristics of patients with high extracellular volume fraction evaluated by cardiac computed tomography for coronary artery evaluation

Abstract Aim To evaluate the distribution of extracellular volume fraction detected via computed tomography, clinical characteristics of high extracellular volume fraction detected via computed tomography, and the rate of incidental detection of cardiac amyloidosis in patients undergoing cardiac computed tomography for coronary artery evaluation. Methods and Results This study included 874 consecutive patients (mean age, 74.4 ± 7.1 years; men, 65%), comprising men aged ≥60 years and women aged ≥70 years, who had undergone cardiac computed tomography between January 2020 and September 2022. The mean extracellular volume fraction detected via computed tomography was 29.7 ± 5.2%, and 108 patients (12.4%) had an extracellular volume fraction detected via computed tomography of ≥35%. Older age (75.9 ± 8.2 years vs. 74.2 ± 6.9 years; P = 0.042), male sex (75.9% vs. 63.0%; P = 0.007), impaired left ventricular ejection fraction, increased high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, and increased left ventricular thickness showed significant associations with an extracellular volume fraction detected via computed tomography of ≥35%. Cardiac amyloidosis was diagnosed incidentally in 15 patients based on an increase in extracellular volume fraction detected via computed tomography. The prevalence of cardiac amyloidosis was 1.7% (15/874) and 14.3% (15/105) in the entire study population and in patients with an extracellular volume fraction detected via computed tomography of ≥35%, respectively. An increase in the extracellular volume fraction detected via computed tomography was suggestive of cardiac amyloidosis. Conclusion Elevated extracellular volume fraction detected via computed tomography, associated with elevated cardiac biomarker levels and myocardial structural changes, may lead to the incidental diagnosis of cardiac amyloidosis.

Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study

BackgroundLong-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment.Methods6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan.ResultsThe plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05).ConclusionsAfter 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Echocardiographic evaluation of myocardial structural and functional changes in patients with stage 5 chronic kidney disease before and after kidney transplantation

Introduction. Chronic kidney disease, stage 5, leads to structural remodeling of the myocardium, and heart failure. Kidney transplantation promotes normalization of structural and functional parameters of the myocardium through reverse remodeling with an improvement of its systolic function.Aim. To evaluate structural and functional changes of the myocardium in patients before and after kidney transplantation, using echocardiography.Material and methods. A retrospective cross-sectional study included 111 individuals of whom 36 patients underwent evaluation for kidney transplant waiting list placement program (Group I), and 51 patients received kidney transplants from deceased donors (Group II). Group III consisted of 24 individuals without kidney pathology. All patients underwent transthoracic two-dimensional echocardiography using the Phillips Epiq 7 device to determine the structural and functional parameters of the heart, including the use of speckle-tracking technique to assess longitudinal and circumferential myocardial deformation of the left ventricle.Results. There were no statistically significant differences in transthoracic echocardiography results between patients in Group I and Group II. When compared to the parameters of patients in Group III, statistically significant differences were found in the following parameters: volume and volume index of the left atrium, end-diastolic volume index, left ventricular mass index, interventricular septum thickness and posterior wall thickness of the left ventricle, as well as diastolic function parameters (E/A). Patients in Group I and Group II had significantly higher values of left atrium diameter: 32 (26.0;38.0) mmHg and 31.0 (27.3;40.0) mmHg, respectively, (p1-2=0.949), while in Group III this parameter value was 22.5 (20.8;25.3) mmHg (p1-3&lt;0.001, p2-3&lt;0.001). Correlation analysis revealed statistically significant correlations between left ventricular mass index and global circumferential strain (r=0.41, p=0.0027), as well as between E/e' ratio and left ventricular mass index (r=0.323, p=0.00197). It was found that after 3 months post kidney transplantation, there was a decrease in the left atrium diameter, volume, and volume index. The values of left atrium diameter immediately after kidney transplantation and after 3 months were 40 (32.5;45) mmHg and 35 (25.5;41.0) mmHg (p=0.049); those of the left atrium volume were 62.5 (50.0;77.3) and 51.5 (47.5;64.5) ml (p=0.03); and those of the left atrium volume index were 33.4 (29.3;40.2) and 28.3 (25.5;33.6) ml/m2 (p=0.01) respectively.Conclusions. Patients with chronic kidney disease stage 5 have a high incidence of functional and structural abnormalities of the left heart chambers; left ventricular mass index positively correlates with E/e' and global circumferential strain. At 3 months after kidney transplantation, there was a slight positive trend manifested in the form of a decrease in left atrium diameter and a decrease in left ventricle volume. Further dynamic study of this group of patients in the long term after kidney transplantation is planned.

16α-OHE1 alleviates hypoxia-induced inflammation and myocardial damage via the activation of β2-Adrenergic receptor

ObjectiveMyocardial injuries resulting from hypoxia are a significant concern, and this study aimed to explore potential protective strategies against such damage. Specifically, we sought to investigate the cardioprotective effects of 16α-hydroxyestrone (16α-OHE1). MethodsMale Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of β2AR were determined in rat hearts and H9C2 cells. The β2AR inhibitor, ICI 118,551, was employed to investigate β2AR's role in 16α-OHE1's cardioprotective effects. ResultsHypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of β2AR expression in both rat hearts and H9C2 cells. However, inhibition of β2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium. ConclusionOur findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through β2ARs, indicating a promising avenue for cardioprotection.

So close, yet so far away: the relationship between MAM and cardiac disease.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Left ventricle function and post-transcriptional events with exercise training in pigs.

Standardized exercise protocols have been shown to improve overall cardiovascular fitness, but direct effects on left ventricular (LV) function, particularly diastolic function and relation to post-transcriptional molecular pathways (microRNAs (miRs)) are poorly understood. This project tested the central hypothesis that adaptive LV remodeling resulting from a large animal exercise training protocol, would be directly associated with specific miRs responsible for regulating pathways relevant to LV myocardial stiffness and geometry. Pigs (n = 9; 25 Kg) underwent a 4 week exercise training protocol (10 degrees elevation, 2.5 mph, 10 min, 5 days/week) whereby LV chamber stiffness (KC) and regional myocardial stiffness (rKm) were measured by Doppler/speckle tracking echocardiography. Age and weight matched non-exercise pigs (n = 6) served as controls. LV KC fell by approximately 50% and rKm by 30% following exercise (both p < 0.05). Using an 84 miR array, 34 (40%) miRs changed with exercise, whereby 8 of the changed miRs (miR-19a, miR-22, miR-30e, miR-99a, miR-142, miR-144, miR-199a, and miR-497) were correlated to the change in KC (r ≥ 0.5 p < 0.05) and mapped to matrix and calcium handling processes. Additionally, miR-22 and miR-30e decreased with exercise and mapped to a localized inflammatory process, the inflammasome (NLRP-3, whereby a 2-fold decrease in NLRP-3 mRNA occurred with exercise (p < 0.05). Chronic exercise reduced LV chamber and myocardial stiffness and was correlated to miRs that map to myocardial relaxation processes as well as local inflammatory pathways. These unique findings set the stage for utilization of myocardial miR profiling to identify underlying mechanisms by which exercise causes changes in LV myocardial structure and function.

Clinical and genetic characterization of patients with catecholaminergic polymorphic ventricular tachycardia: a case series

AIM: of the study was to evaluate the clinical and genetic characteristics, including the development of adverse events and outcomes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).&#x0D; MATERIALS AND METHODS: The clinical phenotype of eight patients with CPVT, two of whom were relatives of probands, was observed over 4 years. The clinical and instrumental study included ECG-12, 24-hour Holter ECG monitoring, genealogical history collection and family history of sudden cardiac death (SCD), transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes, electrophysiologic study according to indications, and ICD monitoring. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.&#x0D; RESULTS: In 8 patients, nucleotide variants of pathogenicity classes III-V were identified according to the ACMG (2015) criteria in the RYR2 gene associated with CPVT. Pathogenic (IV-V class) and likely pathogenic (IV class) mutations in the RYR2 gene were found in 6 (75%) probands, variants with uncertain clinical significance (VUS, class III) were found in 2 patients. At the time of diagnosis, transient QTc interval prolongation of more than 480 ms was detected in 4 (50%) patients; bradycardia less than 54 beats/min — in 2 (25%) patients, sequences of supraventricular tachycardia and ventricular tachyarrhythmia — in 2 (25%) patients. The most severe form of the disease with marked clinical manifestations and an episode of clinical death with subsequent resuscitation, as well as a transient QTc interval prolongation exceeding 500 ms was observed in patients with mutations c.11814C A (p.Ser3938Arg, rs794728704); c.463G A (p.Gly155Arg) and c.14876G A (p.Arg4959Gln, rs794728811) in the RYR2 gene. Three (37.5%) patients underwent ICD implantation; one for primary SCD prevention and two for secondary prevention.&#x0D; CONCLUSION: In this study, the spectrum of clinical manifestations in patients with genetically confirmed CPVT was examined. The findings highlight transient QTc interval extensions, significant sinus bradycardia, and sequences of supraventricular tachyarrhythmias, which can escalate into life-threatening ventricular tachyarrhythmias in CPVT patients.

Brugada syndrome: variability of clinical and genetic characteristics

AIM: To evaluate the clinical characteristics of patients with diverse genetic variants of Brugada syndrome.&#x0D; MATERIALS AND METHODS: 24 patients (17 male and 7 female) aged 18 to 55 years (median age 32.5 [20; 42] years) with a pattern of Brugada syndrome on electrocardiogram were observed for 3 years. From their ECGs, a type 1 pattern was found in 9 (37.5%) of these patients, type 2 pattern in 14 (58.3%) and type 3 pattern only in 1 patient. The clinical and instrumental study included 12-lead electrocardiogram, 24-hour Holter electrocardiogram monitoring, provocative drug test with intravenous administration of sodium channel blockers (novocainamide), electrophysiologic study according to indications, genealogical history collection and family history of sudden cardiac death, transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes. High-throughput sequencing was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.&#x0D; RESULTS: In 15 (62.5%) of the 24 probands included in the study, variants of the nucleotide sequence of pathogenicity classes III–V according to The American College of Medical Genetics and Genomics criteria (2015) were found in genes encoding sodium (SCN5A, SCN10A) and potassium (KCNE3, KCNJ2, KCNJ8, KCNA5) channels, as well as in HCN4 and SNTA1 genes linked with these channels. Moreover, 3 variants were identified in ANK2 gene associated with ankyrinopathies, and 3 variants in DSP and DES genes connected with arrhythmogenic right ventricular cardiomyopathy. Four genetic variants in SCN5A gene were of pathogenicity classes IV and V, the rest were variants of uncertain clinical significance (class III). Six (40.0%) of the 15 genotype-positive patients had several genetic variants. The most severe form of the disease, manifested by the development of ventricular fibrillation with successful resuscitation and subsequent cardioverter-defibrillator implantation, was observed in patients with mutations in SCN5A, SCN10A genes. Recurrent syncope, polymorphic ventricular tachycardia induced by programmed ventricular stimulation during electrophysiologic study, followed by cardioverter-defibrillator implantation were observed in patients with variants KCNJ8 and HCN4, DES and MYH11. In 2 patients with clinical manifestations, no mutations were identified. 13 (54.2%) patients were asymptomatic, while 3 of them had pathogenic and likely pathogenic mutations in SCN5A gene, as well as variants of uncertain clinical significance.&#x0D; CONCLUSION: Thus, this study examined various genetic variants in patients with Brugada syndrome based on their clinical manifestation. The impact of the genotype on the Brugada syndrome phenotype is not unambiguous. The most severe form of the disease with the development of ventricular fibrillation and successful resuscitation with subsequent cardioverter-defibrillator implantation was observed mainly in patients with variants in several genes (SCN5A and JUP, KCNJ8 and HCN4, DES and MYH11). This substantiate the idea that Brugada syndrome, along with monogenic, may also have a polygenic nature of the disease, in which the clinical phenotype is determined by variants in respective genes linked to the onset of cardiovascular disorders.

Evaluation of MR-safe bioptomes for MR-guided endomyocardial biopsy in minipigs: a potential radiation-free clinical approach

BackgroundDiagnostic accuracy of endomyocardial biopsy could improve if clinically safe magnetic resonance (MR)-compatible bioptomes were available. We explored two novel MR-compatible cardiac bioptomes for performance, safety, and clinical viability, employing in vivo minipig trials and phase-contrast synchrotron radiation computed microtomography (SRµCT).MethodsAnalysis of ex vivo obtained pig endomyocardial biopsies was performed using phase-contrast SRµCT and conventional two-dimensional histology. The technical performance was evaluated by measuring volume, inner and outer integrities, compression, and histological diagnostic value in 3 sets (6 per set) of biopsies for each experimental bioptome. The bioptomes were tested in vivo in 3 healthy minipigs per bioptome. The clinical feasibility was evaluated by procedural and cutting success as well as histological diagnostic value.ResultsThe bioptome with the ‘grind-grind’ design achieved similar values to control in compression (p = 0.822), inner (p = 0.628), and outer (p = 0.507), integrities ex vivo. It showed a better performance in the in vivo real-time MRI setting demonstrating a higher cutting success (91.7%) than the ‘grind-anvil’ (86.2%) design. In both ex vivo and in vivo evaluations, the ‘grind-grind’ design displayed sufficient diagnostic value (83% and 95%). The ‘grind-anvil’ design showed adequate diagnostic value both ex vivo and in vivo (78% and 87.5%) but was not comparable to control according to the three-dimensional (3D) analysis.ConclusionA novel MR-compatible bioptome was identified as plausible in a clinical setting. Additionally, SRµCT and subsequent 3D structural analysis could be valuable in the label-free investigation of myocardial tissue at a micrometer level.Relevance statementImplementation of MR-guided biopsy can improve animal studies on structural myocardial changes at any point in an experimental setup. With further improvements in guiding catheters, MR-guided biopsy, using the new bioptome, has a potential to increase quality and diagnostic accuracy in patients both with structural and inflammatory cardiomyopathies.Key points• Novel MR-compatible bioptomes show promise for a clinical application.• SRµCT enabled detailed analysis of endomyocardial biopsies.• The bioptomes showed adequate in vivo performance without major complications.Graphical

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Myocardial structural and functional changes in cardiac amyloidosis - insights from a prospective observational patient registry

Abstract Background Within the last decade, cardiac amyloidosis (CA) has been acknowledged as a significant cause of heart failure and patients who are affected face a dismal prognosis, especially in later stages of the disease. The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time and its' impact on prognosis are lacking. Objectives We aimed to investigate the progression of ECV and its prognostic impact in CA patients. Methods Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification were performed in consecutive CA patients. Results Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%. During a median follow-up period of 12 months, ECV increased significantly in all cohorts (48.0% to 50.5%, p&amp;lt;0.001; 49.0% to 50.5%, p&amp;lt;0.001; 42.6% to 50.6%, p = 0.026). Separate analyses for treatment-naïve (n = 14) and treated (n = 66) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (5.5% versus 2.7%, p = 0.035). Survival analyses demonstrated that median change of ECV was an independent (adjusted for troponin t and NT-proBNP) predictor of outcome in all CA cohorts [total: hazard ratio (HR): 1.114, 95% confidence-interval (CI): 1.045 – 1.189, p&amp;lt;0.001; ATTR: HR: 1.099, 95% CI: 1.014 – 1.192, p = 0.022; AL: HR: 1.142, 95% CI: 1.006 – 1.297, p = 0.040]. Conclusions The present study demonstrates that ECV, quantified by CMR T1 mapping, increases significantly in CA patients over the course of 12 months. While ECV increased, irrespective of amyloid type our analyses showed the highest increase among untreated ATTR patients. Moreover, the change of ECV was an independent predictor of adverse outcomes in AL, as well as ATTR patients emphasizing the usefulness of CMR T1 mapping in the management of CA patients.Figure 1.Dot PlotsFigure 2.Kaplan Meier Curves

Abstract 13751: Clinical Characteristics With High Extracellular Volume Fraction in Patients Who Performed Cardiac Computed Tomography Angiography for the Purpose of Evaluating Coronary Arteries

Background: Cardiac computed tomography angiography (CCTA) is useful for the evaluation of anatomical coronary artery lesions. Recently, extracellular volume fraction by computed tomography (ECV CT ) have become possible by imaging the delay phase after coronary CT angiography. ECV CT has been reported to be useful for detailed examination and prognosis prediction after therapeutic intervention of cardiomyopathy. Cardiac amyloidosis is known as a cardiomyopathy with noticeable increased ECV, and cardiac amyloidosis should be suspected in patients with high ECV. The aim of this study was to evaluate clinical characteristics of high ECV CT and incidental detection of cardiac amyloidosis in patients who underwent CCTA for the purpose of evaluation of coronary arteries. Methods and Results: We examined consecutive 875 patients (mean age; 74.3 ± 7.1 years, men; 64%) who underwent CCCA in men aged ≥ 60 years and women aged ≥ 70 years. ECV CT quantification was performed with pre-contrast and post-contrast delayed phase CT images with the subtraction-derived method. Mean ECV CT was 29.7 ± 5.2%, and a total of 109 patients (12.3%) had ECV CT ≥ 35%. The patients with ECV CT ≥ 35% were significantly older (75.8±8.1 years vs. 74.1±6.9 years; P=0.038) and male dominant 75.4% vs 63.1%; P=0.007). Increased of high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, left ventricular diastolic diameter, left ventricular thickness, impaired left ventricular ejection fraction, and E/e’ were significantly associated with ECV CT ≥ 35%. The prevalence of cardiac amyloidosis was estimated to be at least 1.7% (15/875) in entire study patients and 14.2% (15/106) in patients with ECV CT ≥ 35%. In these cases, increased ECV CT was a clue of the diagnosis of cardiac amyloidosis. Conclusion: CCTA was useful not only for evaluation of coronary arteries but also for evaluation of myocardial properties by ECV CT . Elevated ECV CT was associated with elevated cardiac biomarkers and structural changes of myocardium. There is an incidental diagnosis of cardiac amyloidosis in approximately 1.7% of cases underwent CCTA for the purpose of coronary artery evaluation detected by increased ECV CT .

Association Between Type 2 Diabetes and Changes in Myocardial Structure, Contractile Function, Energetics, and Blood Flow Before and After Aortic Valve Replacement in Patients With Severe Aortic Stenosis.

Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D.

Antifibrotic effects of sodium-glucose cotransporter 2 inhibitors in patients with heart failure

Heart failure (HF) is an urgent public health problem worldwide. A fundamental role in HF progression is played by fibrosis, which causes structural myocardial and vascular changes. In this regard, it seems relevant to search for pathogenetically justified HF therapy, aimed at slowing the myocardial fibrosis progression. The results of EMPA-REG OUTCOME study showed that glucose-lowering drugs, namely sodium-glucose cotransporter 2 (SGLT2) inhibitors, have a positive effect on HF course, reducing cardiovascular mortality and hospitalization rate of patients for decompensated HF. Large-scale studies showed the antifibrotic properties of SGLT2 inhibitors. The review article presents the results of experimental studies on the use of SGLT2 inhibitors in animals. A number of mechanisms for the implementation of the antifibrotic properties of SGLT2 inhibitors affecting the cardiovascular system have been described. It seems relevant to further study SGLT2 inhibitors in clinical trials in order to identify and correct the pathogenetic mechanisms of myocardial fibrosis.

The level of adropin and von Willebrand factor in patients with arterial hypertension, excess body weight, and obesity

Objective. To investigate changes in adropin and von Willebrand factor (vWF) levels in patients with arterial hypertension (AH), excess body weight, and obesity.Material and methods. All patients were divided into two main groups: group 1 included 69 patients with AH and excess body weight; group 2 – 55 people with AH and obesity, and 20 healthy people of the control group. Anthropometric measurement, biochemical blood test, echocardiographic examination of the heart, and enzyme immunoassay (adropin, vWF) were performed.Results. The level of vWF was significantly higher in patients with AH, overweight, and obesity compared to healthy individuals (p=0,001). Meanwhile, the adropin level decreased with increasing BMI. The lowest adropin level was observed in individuals with AH and obesity (p=0,011). Additionally, a significant positive correlation was identified between vWF and the size of the LA (r=0,667; p=0,001), RV (r=0,487; p=0,021), MMLV (r=0,795; p=0,001) and IMMLV (r=0,731; p=0,001), whereas a negative correlation was found with EF (r=-0,461; p=0,031).Conclusions. An increase in vWF level was observed in patients with hypertension, overweight, and obesity which contributes to the emergence of endothelial dysfunction and structural myocardial changes, related to AH. The decrease in adropin level – a regulator of the cardiovascular system functions – was associated with an increase in BMI and elevated BP. Negative correlations were found between adropin and systolic and diastolic blood pressure values. It plays an important role in blood pressure and cardiovascular function regulation.

Diagnostic criteria for proximal left bundle branch block and their significance in predicting the success of cardiac resynchronization therapy

Aim. To develop diagnostic criteria for proximal left bundle branch block (LBBB) based on non-invasive methods and to determine the significance of these criteria in predicting the effect of cardiac resynchronization therapy (CRT).Material and methods. To develop criteria, 58 patients (21 men, mean age, 76,1±7,1 years) with LBBB occurred immediately after transcatheter aortic valve implantation (TAVI) were included. To assess the significance of the developed criteria, the second group included 22 patients (11 men, mean age, 57,9±9,3 years) with dilated cardiomyopathy (DCM), who had indications for CRT. The effectiveness of CRT was assessed by echocardiography 6 months after implantation. All patients in the DCM group and 15 patients in the TAVI group underwent superficial epiand endocardial non-invasive mapping using Amycard 01C EP Lab (EP Solutions SA, Switzerland). Patients in the DCM group underwent contrast-enhanced cardiac magnetic resonance imaging (MRI) before device implantation.Results. The criteria for proximal LBBB included 3 electrocardiographic features: QRS complex &gt;130 ms in women and 140 ms in men, QSor rS-configuration in V1 lead, notch in two or more lateral leads (I, avL, V5, V6), and 2 mapping criteria: characteristic location of block line and delayed activation point. In the DCM group, the criteria were positive in 13 of 22 patients (59%). The developed criteria for proximal LBBB showed a relatively strong, significant relationship with the positive effect of CRT (сhi-square test =5,46, p=0,02, Cramer test =0,5, odds ratio (OR)=15,0, 95% confidence interval (CI), 1,32-169,9, p=0,002). An additional analysis showed that both the criteria for proximal block and CRT effect are associated with myocardial fibrosis according to MRI. In particular, intramural stria-shaped contrast accumulation in the interventricular septum leads to a change in characteristic of proximal block mapping phenomena — displacement of delayed activation point (chi-square test =13,9, p&lt;0,001, Cramer test =0,79) and displacement or absence of conduction block lines (chi-square test =6,92, p=0,009, Cramer test =0,56) and prevents the CRT effect (OR =8,67, 95% CI, 1,05-71,57 p=0,03).Conclusion. Proximal LBBB is only one of the factors determining the effectiveness of CRT. Proximal LBBB may mask significant myocardial structural changes that prevent the CRT success.

Left Ventricular Mass, Myocardial Structure, and Function in Severe Aortic Stenosis: an Echocardiographic and Cardiac Magnetic Resonance Imaging Study

In severe aortic stenosis (AS), there are conflicting data on the prognostic implications of left ventricular (LV) hypertrophy (LVH). We aimed to characterize the LV geometry, myocardial matrix structural changes, and prognostic stratification using cardiac magnetic resonance imaging (CMR) and echocardiography in subjects with severe AS with and without LVH. Consecutive patients who had severe isolated AS and sufficient quality echocardiography and CMR within 6months of each other were evaluated for LVH, cardiac structure, morphology, and late gadolinium-enhancement imaging. Kaplan-Meier curves, linear models, and proportional hazards models were used for prognostic stratification. There were 93 patients enrolled (mean age 74 ± 11years, 48% female), of whom 38 (41%) had a normal LV mass index (LVMI), 41 (44%) had LVH defined at CMR by LVMI >2 SD higher than normal, and 14 (15% of the total) with >4 SD higher than the reference LVMI (severely elevated). The Society of Thoracic Surgeons scores were similar among the LVMI groups. Compared with those with normal LVMI, patients with LVH had higher LV end-diastolic and end-systolic volumes, increased late gadolinium-enhancement burden, and lower LV ejection fraction. Most notably, CMR feature-tracking global radial strain, 2-dimensional speckle-tracking echocardiography global longitudinal strain, and left atrial reservoir function were significantly worse. On the survival analyses, LVMI was not associated with a composite of all-cause mortality and/or heart failure hospitalization. In conclusion, compared with normal LVMI, elevated LVMI was not associated with a higher risk of adverse outcomes.

Automatic left ventricle segmentation via edge‐shape feature‐based fully convolutional neural network

AbstractLeft ventricle (LV) segmentation is essential to identify the cardiac functions for treating cardiovascular disorders. Cardiovascular magnetic resonance (CMRI) imaging is a non‐invasive technique for diagnosing cardiovascular diseases. CMRI is widely used to assess the functional integrity of the left and right ventricles for detecting changes in myocardial structure. Clinical parameters of the LV are often retrieved from CMRI scans, such as LV volumes, and ejection fraction. Moreover, manually segmenting cardiac diseases and evaluating such functions is time‐consuming and difficult for medical professionals. Deep learning networks require a lot of time, cost, and knowledge. To overcome this issue, a novel Edge and Shape feature‐based Fully Convolutional Neural Network (ES‐FCN) has been proposed for automatic LV segmentation. The ES‐FCN model segments MRI images based on edge maps instead of using gray‐scale images, which accelerates the performance of the FCN. The fuzzy‐based canny edge detection algorithm leverages fuzzy logic to detect structural changes in the LV and generate binary images. Additionally, binary‐valued kernels are used for convolution operations, where the binary values are influenced by biases derived from edge map shape descriptors. In ES‐FCN, bias values are learned from ground truth segmentation. The proposed ES‐FCN model achieves the Jaccard indices of 0.9484 ± 0.0188 for the ACDC dataset and 0.9476 ± 0.0237 for the LVSC dataset, and the dice index of 0.9319 ± 0.0188 for the ACDC dataset and 0.9314 ± 0.0237 for LVSC dataset respectively. The experimental results also reveal that the proposed ES‐FCN model is faster and requires minimal resources compared to state‐of‐the‐art models.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.